Publications by authors named "Man Liu"

265 Publications

Magnesium Deficiency Causes a Reversible, Metabolic, Diastolic Cardiomyopathy.

J Am Heart Assoc 2021 Jun 5:e020205. Epub 2021 Jun 5.

Division of Cardiology Department of Medicine The Lillehei Heart InstituteUniversity of Minnesota at Twin Cities Minneapolis MN.

Background Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods and Results C57BL/6J mice were fed with a low Mg (low-Mg, 15-30 mg/kg Mg) or a normal Mg (nl-Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with nl-Mg diet for another 6 weeks. Low-Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl-Mg; <0.0001) with a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl-Mg; =0.011). Cellular ATP was decreased significantly in low-Mg hearts. The changes were accompanied by mitochondrial dysfunction with mitochondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin-binding protein C) was -glutathionylated in low-Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride treatment during low-Mg diet improved cardiac relaxation, increased ATP levels, and reduced -glutathionylated cMyBPC. Conclusions Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.
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http://dx.doi.org/10.1161/JAHA.120.020205DOI Listing
June 2021

Controlled delivery of bone morphogenic protein-2-related peptide from mineralised extracellular matrix-based scaffold induces bone regeneration.

Mater Sci Eng C Mater Biol Appl 2021 Jul 13;126:112182. Epub 2021 May 13.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Ideal bone tissue engineering scaffolds composed of extracellular matrix (ECM) require excellent osteoconductive ability to imitate the bone environment. We developed a mineralised tissue-derived ECM-modified true bone ceramic (TBC) scaffold for the delivery of aspartic acid-modified bone morphogenic protein-2 (BMP-2) peptide (P28) and assessed its osteogenic capacity. Decellularized ECM from porcine small intestinal submucosa (SIS) was coated onto the surface of TBC, followed by mineralisation modification (mSIS/TBC). P28 was subsequently immobilised onto the scaffolds in the absence of a crosslinker. The alkaline phosphatase activity and other osteogenic differentiation marker results showed that osteogenesis of the P28/mSIS/TBC scaffolds was significantly greater than that of the TBC and mSIS/TBC groups. In addition, to examine the osteoconductive capability of this system in vivo, we established a rat calvarial bone defect model and evaluated the new bone area and new blood vessel density. Histological observation showed that P28/mSIS/TBC exhibited favourable bone regeneration efficacy. This study proposes the use of mSIS/TBC loaded with P28 as a promising osteogenic scaffold for bone tissue engineering applications.
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http://dx.doi.org/10.1016/j.msec.2021.112182DOI Listing
July 2021

EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling.

Mol Cancer 2021 May 27;20(1):79. Epub 2021 May 27.

National Translational Science Center for Molecular Medicine, Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China.

Background: Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2.

Methods: Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 (Eya2) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis.

Results: A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size (P = 0.001), Barcelona Clinic Liver Cancer stage (P = 0.016) and tumor differentiation (P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients (P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway.

Conclusions: In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.
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http://dx.doi.org/10.1186/s12943-021-01377-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157759PMC
May 2021

Radix Astragali polysaccharide RAP directly protects hematopoietic stem cells from chemotherapy-induced myelosuppression by increasing FOS expression.

Int J Biol Macromol 2021 May 24;183:1715-1722. Epub 2021 May 24.

School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong 999077, Hong Kong, China. Electronic address:

Radix Astragali polysaccharide RAP has been reported to play a crucial role in hematopoiesis without a clear mechanism. In this study, RAP's effects to enhance the recovery of cyclophosphamide (Cy)-suppressed bone marrow and blood cells is confirmed in vivo first. Confocal micrographs demonstrated the interesting direct binding of FITC-RAP to hematopoietic stem cells (HSC) in bone marrow. RAP protects both mice and human HSC in terms of cell morphology, proliferation, and apoptosis. RNA-sequencing and shRNA approaches revealed FOS to be a key regulator in RAP's protection. These evidences provide an unreported mechanism that RAP directly protects hematopoietic stem cells from chemotherapy-induced myelosuppression by increasing FOS expression.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.120DOI Listing
May 2021

Two Enhancers Regulate Genes Expression During Retinoic Acid-Induced Early Embryonic Stem Cells Differentiation Through Long-Range Chromatin Interactions.

Stem Cells Dev 2021 May 24. Epub 2021 May 24.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.

Homeobox B cluster () genes play important roles in retinoic acid (RA)-induced early embryonic stem cells (ESCs) differentiation. Knowledge of regulation network of is important to further unveil the mechanism of ESCs differentiation. In this study, we identified two enhancers that were activated by RA treatment and 4C data showed long-range interactions between genes and the two enhancers. CRISPR/Cas9-mediated individual or compound deletion of the two enhancers significantly inhibits gene expression, and transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in the enhancer KO cells. We propose new mechanism by which two enhancers regulate gene expression by different regulation modes during RA-induced early ESCs differentiation through long-range chromatin interactions.
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http://dx.doi.org/10.1089/scd.2021.0020DOI Listing
May 2021

A spatiotemporal ensemble model to predict gross beta particulate radioactivity across the contiguous United States.

Environ Int 2021 May 19;156:106643. Epub 2021 May 19.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02114, USA.

Particulate radioactivity, a characteristic of particulate matter, is primarily determined by the abundance of radionuclides that are bound to airborne particulates. Exposure to high levels of particulate radioactivity has been associated with negative health outcomes. However, there are currently no spatially and temporally resolved particulate radioactivity data for exposure assessment purposes. We estimated the monthly distributions of gross beta particulate radioactivity across the contiguous United States from 2001 to 2017 with a spatial resolution of 32 km, via a multi-stage ensemble-based model. Particulate radioactivity was measured at 129 RadNet monitors across the contiguous U.S. In stage one, we built 264 base learning models using six methods, then selected nine base models that provide different predictions. In stage two, we used a non-negative geographically and temporally weighted regression method to aggregate the selected base learner predictions based on their local performance. The results of block cross-validation analysis suggested that the non-negative geographically and temporally weighted regression ensemble learning model outperformed all base learning model with the smallest rooted mean square error (0.094 mBq/m). Our model provided an accurate estimation of particulate radioactivity, thus can be used in future health studies.
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http://dx.doi.org/10.1016/j.envint.2021.106643DOI Listing
May 2021

Genome wide analysis of kinesin gene family in Citrullus lanatus reveals an essential role in early fruit development.

BMC Plant Biol 2021 May 10;21(1):210. Epub 2021 May 10.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Background: Kinesin (KIN) as a motor protein is a versatile nano-machine and involved in diverse essential processes in plant growth and development. However, the kinesin gene family has not been identified in watermelon, a valued and nutritious fruit, and yet their functions have not been characterized. Especially, their involvement in early fruit development, which directly determines the size, shape, yield and quality of the watermelon fruit, remains unclear.

Results: In this study, we performed a whole-genome investigation and comprehensive analysis of kinesin genes in C. lanatus. In total, 48 kinesins were identified and categorized into 10 kinesin subfamilies groups based on phylogenetic analysis. Their uneven distribution on 11 chromosomes was revealed by distribution analysis. Conserved motif analysis showed that the ATP-binding motif of kinesins was conserved within all subfamilies, but not the microtubule-binding motif. 10 segmental duplication pairs genes were detected by the syntenic and phylogenetic approaches, which showed the expansion of the kinesin gene family in C. lanatus genome during evolution. Moreover, 5 ClKINs genes are specifically and abundantly expressed in early fruit developmental stages according to comprehensive expression profile analysis, implying their critical regulatory roles during early fruit development. Our data also demonstrated that the majority of kinesin genes were responsive to plant hormones, revealing their potential involvement in the signaling pathways of plant hormones.

Conclusions: Kinesin gene family in watermelon was comprehensively analyzed in this study, which establishes a foundation for further functional investigation of C. lanatus kinesin genes and provides novel insights into their biological functions. In addition, these results also provide useful information for understanding the relationship between plant hormone and kinesin genes in C. lanatus.
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http://dx.doi.org/10.1186/s12870-021-02988-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108342PMC
May 2021

Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array.

Front Immunol 2021 23;12:658922. Epub 2021 Apr 23.

Department of Oncology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

Substantial studies indicate that autoantibodies to tumor-associated antigens (TAAbs) arise in early stage of lung cancer (LC). However, since single TAAbs as non-invasive biomarkers reveal low diagnostic performances, a panel approach is needed to provide more clues for early detection of LC. In the present research, potential TAAbs were screened in 150 serum samples by focused protein array based on 154 proteins encoded by cancer driver genes. Indirect enzyme-linked immunosorbent assay (ELISA) was used to verify and validate TAAbs in two independent datasets with 1,054 participants (310 in verification cohort, 744 in validation cohort). In both verification and validation cohorts, eight TAAbs were higher in serum of LC patients compared with normal controls. Moreover, diagnostic models were built and evaluated in the training set and the test set of validation cohort by six data mining methods. In contrast to the other five models, the decision tree (DT) model containing seven TAAbs (TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1), built in the training set, yielded the highest diagnostic value with the area under the receiver operating characteristic curve (AUC) of 0.897, the sensitivity of 94.4% and the specificity of 84.9%. The model was further assessed in the test set and exhibited an AUC of 0.838 with the sensitivity of 89.4% and the specificity of 78.2%. Interestingly, the accuracies of this model in both early and advanced stage were close to 90%, much more effective than that of single TAAbs. Protein array based on cancer driver genes is effective in screening and discovering potential TAAbs of LC. The TAAbs panel with TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1 is excellent in early detection of LC, and they might be new target in LC immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.658922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102818PMC
April 2021

Predicting Monthly Community-Level Domestic Radon Concentrations in the Greater Boston Area with an Ensemble Learning Model.

Environ Sci Technol 2021 May 3;55(10):7157-7166. Epub 2021 May 3.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, 401 Park Drive, Boston, Massachusetts 02114, United States.

Inhaling radon and its progeny is associated with adverse health outcomes. However, previous studies of the health effects of residential exposure to radon in the United States were commonly based on a county-level temporally invariant radon model that was developed using measurements collected in the mid- to late 1980s. We developed a machine learning model to predict monthly radon concentrations for each ZIP Code Tabulation Area (ZCTA) in the Greater Boston area based on 363,783 short-term measurements by Spruce Environmental Technologies, Inc., during the period 2005-2018. A two-stage ensemble-based model was developed to predict radon concentrations for all ZCTAs and months. Stage one included 12 base statistical models that independently predicted ZCTA-level radon concentrations based on geological, architectural, socioeconomic, and meteorological factors for each ZCTA. Stage two aggregated the predictions of these 12 base models using an ensemble learning method. The results of a 10-fold cross-validation showed that the stage-two model has a good prediction accuracy with a weighted of 0.63 and root mean square error of 22.6 Bq/m. The community-level time-varying predictions from our model have good predictive precision and accuracy and can be used in future prospective epidemiological studies in the Greater Boston area.
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http://dx.doi.org/10.1021/acs.est.0c08792DOI Listing
May 2021

The Anti-Inflammatory Effect and Mucosal Barrier Protection of RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis.

Front Cell Infect Microbiol 2021 25;11:647048. Epub 2021 Mar 25.

College of Basic Medical Science, Dalian Medical University, Dalian, China.

This study aimed at determining the beneficial effect of (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (10 and 10 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (, , , and ) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4 T cells in Peyer's patches (PPs) , which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.
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http://dx.doi.org/10.3389/fcimb.2021.647048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027357PMC
March 2021

Leaky Gut Driven by Dysbiosis Augments Activation and Accumulation of Liver Macrophages RIP3 Signaling Pathway in Autoimmune Hepatitis.

Front Immunol 2021 25;12:624360. Epub 2021 Mar 25.

Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.

The gut-liver axis has been increasingly recognized as a major autoimmunity modulator. However, the implications of intestinal barrier in the pathogenesis of autoimmune hepatitis (AIH) remain elusive. Here, we investigated the functional role of gut barrier and intestinal microbiota for hepatic innate immune response in AIH patients and murine models. In this study, we found that AIH patients displayed increased intestinal permeability and pronounced RIP3 activation of liver macrophages. In mice models, intestinal barrier dysfunction increased intestinal bacterial translocation, thus amplifying the hepatic RIP3-mediated innate immune response. Furthermore, GSK872 dampened RIP3 activation and ameliorated the activation and accumulation of liver macrophages and experiments. Strikingly, broad-spectrum antibiotic ablation significantly alleviated RIP3 activation and liver injury, highlighting the causal role of intestinal microbiota for disease progression. Our results provided a potentially novel mechanism of immune tolerance breakage in the liver the gut-liver axis. In addition, we also explored the therapeutic and research potentials of regulating the intestinal microbiota for the therapy of AIH.
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http://dx.doi.org/10.3389/fimmu.2021.624360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027109PMC
March 2021

Sources of indoor PM gross α and β activities measured in 340 homes.

Environ Res 2021 Jun 2;197:111114. Epub 2021 Apr 2.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Particle radioactivity (PR) exposure has been linked to adverse health effects. PR refers to the presence of α- and β-emitting radioisotopes attached to fine particulate matter (PM). This study investigated sources contributing to indoor PM gross α- and β-radioactivity levels. We measured activity from long-lived radon progeny radionuclides from archived PM samples collected in 340 homes in Massachusetts during the period 2006-2010. We analyzed the data using linear mixed effects models and positive matrix factorization (PMF) analysis. Indoor PM gross α-activity levels were correlated with sulfur (S), iron (Fe), bromine (Br), vanadium (V), sodium (Na), lead (Pb), potassium (K), calcium (Ca), silicon (Si), zinc (Zn), arsenic (As), titanium (Ti), radon (Rn) and black carbon (BC) concentrations (p <0.05). Indoor PM β-activity was correlated with S, As, antimony (Sb), Pb, Br and BC. We identified four indoor PM sources: outdoor air pollution (62%), salt aerosol source (14%), fireworks and environmental tobacco smoke (7%) and indoor mixed dust (17%). Outdoor air pollution was the most significant contributor to indoor PM α- and β-activity levels. The contributions of this source were during the summer months and when windows were open. Indoor mixed dust was also found to contribute to PM α-activity. PM α-activity was further associated with radon during winter months, showing radon's important role as an indoor source of ionizing radiation.
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http://dx.doi.org/10.1016/j.envres.2021.111114DOI Listing
June 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

N-n-Butyl haloperidol iodide ameliorates liver fibrosis and hepatic stellate cell activation in mice.

Acta Pharmacol Sin 2021 Mar 23. Epub 2021 Mar 23.

Department of Pharmacology, Shantou University Medical College, Shantou, 515041, China.

N-n-Butyl haloperidol iodide (F) is a novel compound that has antiproliferative and antifibrogenic activities. In this study we investigated the therapeutic potential of F against liver fibrosis in mice and the underlying mechanisms. Two widely used mouse models of fibrosis was established in mice by injection of either carbon tetrachloride (CCl) or thioacetamide (TAA). The mice received F (0.75, 1.5 or 3 mg·kg·d, ip) for 4 weeks of fibrosis induction. We showed that F administration dose-dependently ameliorated CCl- or TAA-induced liver fibrosis, evidenced by significant decreases in collagen deposition and c-Jun, TGF-β receptor II (TGFBR2), α-smooth muscle actin (α-SMA), and collagen I expression in the liver. In transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 cells (a human hepatic stellate cell line) and primary mouse hepatic stellate cells, treatment with F (0.1, 1, 10 μM) concentration-dependently inhibited the expression of α-SMA, and collagen I. In LX-2 cells, F inhibited TGF-β/Smad signaling through reducing the levels of TGFBR2; pretreatment with LY2109761 (TGF-β signaling inhibitor) or SP600125 (c-Jun signaling inhibitor) markedly inhibited TGF-β1-induced induction of α-SMA and collagen I. Knockdown of c-Jun decreased TGF-β signaling genes, including TGFBR2 levels. We revealed that c-Jun was bound to the TGFBR2 promoter, whereas F suppressed the binding of c-Jun to the TGFBR2 promoter to restrain TGF-β signaling and inhibit α-SMA and collagen I upregulation. In conclusion, the therapeutic benefit of F against liver fibrosis results from inhibition of c-Jun expression to reduce TGFBR2 and concomitant reduction of the responsiveness of hepatic stellate cells to TGF-β1. F may thus be a potentially new effective pharmacotherapy for human liver fibrosis.
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http://dx.doi.org/10.1038/s41401-021-00630-7DOI Listing
March 2021

Recent development in biological activities and safety concerns of perillaldehyde from perilla plants: A review.

Crit Rev Food Sci Nutr 2021 Mar 22:1-13. Epub 2021 Mar 22.

School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu Province, PR China.

Monoterpene Perillaldehyde (PAE) is a major component of the essential oil extracted from perilla plants (), which has been used as a leafy vegetable and a medicinal agent. PAE has gained a lot of attention in recent years because of its antifungal and other microbial activities and, human health benefits. PAE has also been used as food additives, perfume ingredients, and traditional medicine concoctions. Biological analyses of PAE have revealed that it has good antioxidant activities and can serve as organic fruit and food preservative. Animal studies indicated potent anticancer, anti-depressant, and anti-inflammatory effects of PAE. Also, PAE is certified "generally recognized as safe" (GRAS) and not mutagenic. However, moderation during usage is advisable, as minor adverse effects are associated with a very high dosage. Despite the newly reported findings, its properties have not been thoroughly summarized and reviewed. Also, clinical trials and official large-scale field applications of PAE in the agricultural sectors are yet to be reported. In this review, updated PAE research progress was provided, focusing on its antifungal and other antimicrobial properties and the mechanisms behind it, phytochemical profile, pharmacological effects, and safety concerns.HighlightsIsolation and recovery techniques of PAE from perilla plants have been developed and improved in recent years.PAE is a potential anti-oxidant and antifungal agent that can be widely used in the food industry.PAE can be developed into drug ingredients for pharmaceutical industries due to its anti-inflammatory, anti-cancer and anti-depressant activities.PAE can be safely used in human when low and moderate dosage is used.
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http://dx.doi.org/10.1080/10408398.2021.1900060DOI Listing
March 2021

UBE2S interacting with TRIM28 in the nucleus accelerates cell cycle by ubiquitination of p27 to promote hepatocellular carcinoma development.

Signal Transduct Target Ther 2021 Feb 16;6(1):64. Epub 2021 Feb 16.

National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.

Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine. However, identifying a key driver gene or mutation that can be used for hepatocellular carcinoma (HCC) treatment remains difficult. Here, we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S (p. Gly57Ala and p. Lys63Asn). Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious. Further, we observed that wild-type UBE2S, especially in the nucleus, was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC. Functional assays revealed that overexpression of UBE2S promoted the proliferation, invasion, metastasis, and G1/S phase transition of HCC cells in vitro, and promoted the tumor growth significantly in vivo. Mechanistically, UBE2S interacted with TRIM28 in the nucleus, both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression. Most importantly, the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen (HTS) to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo, which may represent a promising strategy for HCC therapy.
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http://dx.doi.org/10.1038/s41392-020-00432-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884418PMC
February 2021

Identification of tumor-associated antigens of lung cancer: SEREX combined with bioinformatics analysis.

J Immunol Methods 2021 May 12;492:112991. Epub 2021 Feb 12.

School of Basic Medical Sciences & Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China; BGI, Zhengzhou University, Zhengzhou 450052, Henan, China; Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address:

The aim of this study is to identify novel tumor-associated antigens (TAAs) of lung cancer by using serological analysis of recombinant cDNA expression library (SEREX) and bioinformatics analysis as well as to explore their humoral immune response. SEREX and pathway enrichment analysis were used to immunoscreen TAAs of lung cancer and elaborate their function in biological pathways, respectively. Subsequently, the sera level of autoantibodies against the selected TAAs (TOP2A, TRIM37, HSP90AB1, EEF1G and TPP1) was detected by immunoserological analysis to explore the immune response of these antigens. The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) database were applied to explore the mRNA and protein expression level of TOP2A, TRIM37 and HSP90AB1 in tissues, respectively. Seventy positive clones were identified by SEREX which contain 63 different genes, and 35 genes of them have been reported. These 35 genes were mainly related to regulation of different transcription factor and performed enrichment in legionellosis, RNA transport, IL-17 signaling pathway via enrichment analysis. Additionally, the positive rate of autoantibodies against TOP2A, TRIM37 and HSP90AB1 in lung cancer patients were typically higher than normal control (NC; P < 0.05). Moreover, the combination of the autoantibodies against TOP2A, TRIM37 and HSP90AB1 possessed an excellent diagnostic performance with sensitivity of 84% and specificity of 60%. The mRNA expression level of TOP2A was obviously unregulated in squamous cell carcinoma (SCC) tissues and adenocarcinoma (ADC) tissues compared to normal tissues (P < 0.05). In addition, TRIM37 and HSP90AB1 also showed a significant difference between SCC and NC at the mRNA expression level (P < 0.05). This study combining comprehensive autoantibody and gene expression assays has added to the growing list of lung cancer antigens, which may aid the development of diagnostic and immunotherapeutic targets for lung cancer patients.
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http://dx.doi.org/10.1016/j.jim.2021.112991DOI Listing
May 2021

CTCF-binding element regulates ESC differentiation via orchestrating long-range chromatin interaction between enhancers and HoxA.

J Biol Chem 2021 Feb 10:100413. Epub 2021 Feb 10.

College of Life Sciences, Nankai University, 94 Weijin Road, 300071, Tianjin, China. Electronic address:

Proper expression of Homeobox A cluster genes (HoxA) is essential for embryonic stem cell (ESC) differentiation and individual development. However, mechanisms controlling precise spatiotemporal expression of HoxA during early ESC differentiation remain poorly understood. Herein, we identified a functional CTCF-binding element (CBE) closest to the 3'-end of HoxA within the same topologically associated domain (TAD) in ESC. CRISPR-Cas9-mediated deletion of CBE significantly upregulated HoxA expression and enhanced early ESC differentiation induced by retinoic acid (RA) relative to wild-type cells. Mechanistic analysis by chromosome conformation capture assay (Capture-C) revealed that CBE deletion decreased interactions between adjacent enhancers, enabling formation of a relatively loose enhancer-enhancer interaction complex (EEIC), which overall increased interactions between that EEIC and central regions of HoxA chromatin. These findings indicate that CBE organizes chromatin interactions between its adjacent enhancers and HoxA. Furthermore, deletion of those adjacent enhancers synergistically inhibited HoxA activation, suggesting that these enhancers serve as an EEIC required for RA-induced HoxA activation. Collectively, these results provide new insight into RA-induced HoxA expression during early ESC differentiation, also highlight precise regulatory roles of the CTCF-binding element in orchestrating high-order chromatin structure.
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http://dx.doi.org/10.1016/j.jbc.2021.100413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960549PMC
February 2021

Comparison of the oncological, perioperative and functional outcomes of partial nephrectomy versus radical nephrectomy for clinical T1b renal cell carcinoma: A systematic review and meta-analysis of retrospective studies.

Asian J Urol 2021 Jan 4;8(1):117-125. Epub 2019 Dec 4.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: To conduct a meta-analysis assessing the perioperative, functional and oncological outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for T1b tumours. The primary endpoints were the oncological outcomes. The secondary endpoints were the perioperative and functional outcomes.

Methods: A systematic literature review was performed by searching multiple databases through February 2019 to identify eligible comparative studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Identified reports were assessed according to the Newcastle-Ottawa Scale for nonrandomized controlled trials.

Results: Overall, 13 retrospective cohort studies were included in the analysis. Patients undergoing PN were younger (weighted mean difference [WMD] -3.49 years, 95% confidence interval [CI] -5.16 to -1.82; <0.0001) and had smaller masses (WMD -0.45 cm, 95% CI -0.59 to -0.31; <0.0001). There were no differences in the oncological outcome, which was demonstrated by progression-free survival (hazard ratio [HR] 0.70; =0.22), cancer-specific mortality (HR 0.91; =0.57) and all-cause mortality (HR 1.01; =0.96). The two procedures were similar in estimated blood loss (WMD -16.47 mL; =0.53) and postoperative complications (risk ratio [RR] 1.32; =0.10), and PN provided better renal function preservation and was related to a lower likelihood of chronic kidney disease onset (RR 0.38; =0.006).

Conclusion: PN is an effective treatment for T1b tumours because it offers similar surgical morbidity, equivalent cancer control, and better renal preservation compared to RN.
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http://dx.doi.org/10.1016/j.ajur.2019.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859367PMC
January 2021

Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk.

JACC Basic Transl Sci 2021 Jan 20;6(1):42-52. Epub 2021 Jan 20.

Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2 leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1β mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.
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http://dx.doi.org/10.1016/j.jacbts.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838050PMC
January 2021

Humoral immune response to epidermal growth factor receptor in lung cancer.

Immunol Res 2021 Feb 25;69(1):71-80. Epub 2021 Jan 25.

Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China.

The aim of this study was to explore the potential value of autoantibody to epidermal growth factor receptor (EGFR) in the diagnosis of lung cancer (LC) and its relation with EGFR mutations. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of autoantibody to EGFR in sera from 254 LC patients and 222 normal controls (NCs). Besides, the mRNA and protein levels of EGFR were investigated in Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) database, respectively. The level of autoantibody to EGFR (anti-EGFR) in LC even different types of LC was obviously higher than that in NC (P < 0.05). The area under the curve (AUC) of anti-EGFR was 0.695 (95% CI 0.645-0.742) when comparing LC patients with NC, while the AUC of carcinoembryonic antigen (CEA) was 0.681 (95% CI 0.629-0.730). Moreover, by integrating anti-EGFR with CEA to diagnose LC, the AUC was up to 0.784 (95% CI 0.737-0.826). However, the expression level of autoantibody to EGFR had no difference between LC patients with and without EGFR gene mutation (P > 0.05). EGFR mRNA expression level was obviously upregulated in squamous cell carcinoma (SCC) tissues compared with normal tissues (P < 0.05), but not in adenocarcinoma (ADC) (P > 0.05). The study confirmed that anti-EGFR could be a potential biomarker for LC diagnosis; additionally, it could improve the diagnostic value of CEA in clinical work.
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http://dx.doi.org/10.1007/s12026-021-09174-8DOI Listing
February 2021

Blockade of Macrophage CD147 Protects Against Foam Cell Formation in Atherosclerosis.

Front Cell Dev Biol 2020 8;8:609090. Epub 2021 Jan 8.

Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.

The persistence of macrophage-derived foam cells in the artery wall fuels atherosclerosis development. However, the mechanism of foam cell formation regulation remains elusive. We are committed to determining the role that CD147 might play in macrophage foam cell formation during atherosclerosis. In this study, we found that CD147 expression was primarily increased in mouse and human atherosclerotic lesions that were rich in macrophages and could be upregulated by ox-LDL. High-throughput compound screening indicated that ox-LDL-induced CD147 upregulation in macrophages was achieved through PI3K/Akt/mTOR signaling. Genetic deletion of macrophage protected against foam cell formation by impeding cholesterol uptake, probably through the scavenger receptor CD36. The opposite effect was observed in primary macrophages isolated from macrophage-specific -overexpressing mice. Moreover, bioinformatics results indicated that CD147 suppression might exert an atheroprotective effect via various processes, such as cholesterol biosynthetic and metabolic processes, LDL and plasma lipoprotein clearance, and decreased platelet aggregation and collagen degradation. Our findings identify CD147 as a potential target for prevention and treatment of atherosclerosis in the future.
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http://dx.doi.org/10.3389/fcell.2020.609090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820343PMC
January 2021

The complete chloroplast genome of a medicinal plant (Ranunculaceae).

Mitochondrial DNA B Resour 2020 May 13;5(3):2065-2066. Epub 2020 May 13.

College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.

has long-term been used in Chinese traditional medicine with the effects of anticancer, anti-inflammatory, antimicrobial properties, and immune regulation. However, the genomic information of this species is limited, which hinders its further medicinal application. In the present study, the complete chloroplast genome of was sequenced and assembled. The genome size was 157,614 bp in length, consisting of a pair of inverted repeat regions (IR, 31,184 bp), a large single copy (LSC, 79,055 bp), and a small single copy (SSC, 16,191 bp). A total of 138 genes were annotated, including 90 protein-coding genes, 40 tRNA genes, and eight rRNA genes. The GC content of the genome was 37.74%. A phylogenetic analysis on the basis of the whole chloroplast genome sequences further suggested a close relationship between , , and . Collectively, the chloroplast genome provided new genomic resources which will improve its research and application in the future.
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http://dx.doi.org/10.1080/23802359.2020.1763869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781952PMC
May 2020

Constructing a Core Collection of the Medicinal Plant Using Genetic and Metabolic Data.

Front Plant Sci 2020 23;11:600249. Epub 2020 Dec 23.

College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.

is an important medicinal plant in Chinese traditional medicine. Its roots, which are known as in Chinese, are broadly applied to treat inflammation, arthritis, and headache. With increasing market demand, the wild resources of have been overexploited, and conservation, assessment of genetic resources and breeding for this species is needed. Here, we sequenced the transcriptome of and developed simple sequence repeat (SSR) markers from it to construct a core collection based on 208 samples collected from Changyang-related regions. A total of 132 alleles were obtained for 17 SSR loci used with the polymorphic information content () ranging from 0.44 to 0.83. Abundant genetic diversity was inferred by Shannon's information index (1.51), observed (0.57) and expected heterozygosity (0.72). The clustering analysis resulted into two sample groups and analysis of molecular variance (AMOVA) showed only 6% genetic variation existed among populations. A further metabolic analysis of these samples revealed the main coumarin contents, such as osthole and columbianadin. According to the genetic and metabolic data, we adopted the least distance stepwise sampling strategy to construct seven preliminary core collections, of which the 20CC collection, which possessed 42 individuals accounting for 90.20% of the genetic diversity of the original germplasm, represented the best core collection. This study will contribute to the conservation and management of wild germplasm resources and provide a material basis for future selection and breeding of this medicinal plant.
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http://dx.doi.org/10.3389/fpls.2020.600249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785966PMC
December 2020

Identifying the sources of nitrate contamination using a combined dual isotope, chemical and Bayesian model approach in a tropical agricultural river: Case study in the Mun River, Thailand.

Sci Total Environ 2021 Mar 13;760:143938. Epub 2020 Dec 13.

Isotope Bioscience Laboratory-ISOFYS, Faculty of Bioscience Engineering, Ghent University, Gent 9000, Belgium.

Environmental issues triggered by increasing nitrate in agricultural river has become global concern. Identifying nitrate sources and transformation are crucial for water sources protection and eliminating nitrate contamination in an agricultural watershed. In this study, chemical and dual isotopic compositions of nitrate were employed to trace the nitrate sources and transformation processes, and proportional contribution of NO source were estimated by SIAR based on Bayesian model. NH concentrations in middle Mun and lower Mun in wet season were significantly higher than NO, suggesting enhanced runoff processes by flood promote agricultural fertilized NH leaching into the river. Higher Cl concentration and NO/Cl indicated that manure and sewage was the dominate nitrate source in the Lam Takhong River and the upper Mun. The overall values of δN-NO and δO-NO ranged from -3.9‰ to +16.6‰ and from -5.2‰ to +40.0‰, respectively. The results of nitrate isotopes indicated that NO mainly originated from soil N nitrogen, chemical fertilizer, and manure and sewage wastes. Spatially, soil N and chemical fertilizer contributed the most nitrate in the mainstream of lower Mun, middle Mun, and the Lam Takhong River; whereas over 60% of nitrate was derived from manure and sewage in the upper Mun. The spatial variation of water discharge and rainfall, together with the nitrate concentration and isotopes inferred that the nitrate sources and transformations in rain-fed river in tropical zone were distinguished from other rivers. High water discharge driven by rainfall events accelerated the nitrate export and the contribution of atmospheric deposition in wet season, and enlarged the contribution of manure and sewage in dry season. This study provided an example for further researches and approaches to assess the effects of tropical climate and agriculture on nitrate accumulation in watershed.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143938DOI Listing
March 2021

Serum MiR-4687-3p Has Potential for Diagnosis and Carcinogenesis in Non-small Cell Lung Cancer.

Front Genet 2020 23;11:597508. Epub 2020 Nov 23.

Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, China.

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, = 10; the healthy, = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, = 30; the healthy, = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543-0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues ( < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.
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http://dx.doi.org/10.3389/fgene.2020.597508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721467PMC
November 2020

Measurement of the gross alpha activity of the fine fractions of road dust and near-roadway ambient particle matter.

J Air Waste Manag Assoc 2021 Feb;71(2):147-155

Department of Environmental Health, Harvard T.H. Chan School of Public Health , Boston, MA, USA.

Traffic-related air pollution, including direct exhaust emissions and road dust (RD), impacts individuals living near busy roads. We recently conducted a study to investigate the sources and composition of tailpipe and non-tailpipe traffic emissions, where we collected and analyzed samples of ambient air fine particulate matter (PM) and fine RD (RD) at different distances from major roadways. We analyzed a subset of the samples, including those collected at the roadside and local background, for their alpha activity level. Subsequently, we investigated whether there is a distance-related decay in the alpha activity in RD or PM similar to those observed for traffic-related species in PM and RD. We found that the alpha activity of ambient air PM (Bq/mg) was more than an order of magnitude higher than the activity level of the corresponding RD sample, suggesting that PM may be more toxic than RD. Using mixed-effects regression models, we found that ambient PM alpha activity was significantly higher during the cold months than during warm months, and that the background was higher than the roadside (though not significantly). In contrast, the RD alpha activity was significantly higher at the background site compared to the roadside but was not significantly affected by season. In addition to sampling position, both Zn and elemental carbon (EC) were significant predictors of RD alpha activity. In addition, the roadside RD activity levels were found to be higher at highways as compared to secondary roads. While traffic-related emissions do not appear to be significant sources of either ambient PM or RD alpha activity, the RD results suggest that traffic-related particles may contribute to RD alpha-activity. : Many studies have reported the effects of traffic-related particulate matter (PM) on human health, and there is growing interest in the health effects of exposure to environmental PM alpha activity. This is the first study to report on the alpha activity of road dust (RD) or near-roadway ambient PM. We found that the alpha activity of ambient PM is twenty times higher than RD, suggesting that ambient PM may be more toxic. In PM and RD, the alpha activities were higher at background sites than at the roadside, indicating that traffic-related emissions are not a significant source of particulate radioactivity.
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http://dx.doi.org/10.1080/10962247.2020.1850543DOI Listing
February 2021

Creation of Bony Microenvironment with Extracellular Matrix Doped-Bioactive Ceramics to Enhance Osteoblast Behavior and Delivery of Aspartic Acid-Modified BMP-2 Peptides.

Int J Nanomedicine 2020 29;15:8465-8478. Epub 2020 Oct 29.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.

Introduction: Decellularized matrix from porcine small intestinal submucosa (SIS) endows scaffolds with an ECM-like surface, which enhances stem cell self-renewal, proliferation, and differentiation. Mesoporous bioactive glass (MBG) is extensively recognized as an excellent bio-ceramic for fabricating bone grafts.

Materials And Methods: In the current study, SIS was doped on an MBG scaffold (MBG/SIS) using polyurethane foam templating and polydopamine chemistry method. To mimic the bony environment of a natural bone matrix, an ECM-inspired delivery system was constructed by coupling the BMP2-related peptide P28 to a heparinized MBG/SIS scaffold (MBG/SIS-H-P28). The release of P28 from MBG/SIS-H-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells were investigated in vitro and in vivo.

Results: Our research indicated that the novel tissue-derived ECM scaffold MBG/SIS has a hierarchical and interconnected porous architecture, and superior biomechanical properties. MBG/SIS-H-P28 released P28 in a controlled manner, with the long-term release time of 40 d. The results of in vitro experiments showed improvements in cell proliferation, cell viability, alkaline phosphatase activity, and mRNA expression levels of osteogenesis-related genes (, and ) compared to those of MBG/SIS or MBG/SIS-P28 and MBG/SIS-H-P28. The in vivo results demonstrated that MBG/SIS-H-P28 scaffolds evidently increased bone formation in rat calvarial critical-sized defect compared to that in controls.

Conclusion: MBG/SIS-H-P28 scaffolds show potential as ideal platforms for delivery of P28 and for providing a bony environment for bone regeneration.
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http://dx.doi.org/10.2147/IJN.S272571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605642PMC
November 2020

Hsa_circ_0002060 Knockdown Ameliorates Osteoporosis by Targeting MiR-198-5p.

Biol Pharm Bull 2021 Jan 5;44(1):88-95. Epub 2020 Nov 5.

Chemical College, Shenzhen Polytechnic.

Osteoporosis (OP) is increasingly becoming one of a major health concerns all over the world. However, the limitations of current therapeutic drugs for OP are including considerable side effects and low efficacy. Therefore, it is required to develop new therapeutic drugs for OP. This study aimed to investigate the role of hsa_circ_0002060 in the regulation of osteoporosis. Osteoblast cells (hFOB 1.19) were transfected with hsa_circ_0002060 small interfering RNA (siRNA), following by stimulated with dexamethasone (DEX) to mimic OP in vitro. Cell counting kit-8, apoptosis, and JC-1 mitochondrial membrane potential assays were used to evaluate the cell viability, apoptosis, and mitochondrial membrane potential, respectively. Western blot was conducted to detect the expression of proteins. In addition, the levels of reactive oxygen species, superoxide dismutase, glutathione and malondialdehyde were measured with enzyme-linked immunosorbent assay (ELISA). The putative target of hsa_circ_0002060 was verified by dual luciferase reporter assay and RNA pull down. At last, the role of hsa_circ_0002060 in the progression of OP was investigated with an ovariectomy (OVX)-induced OP mouse model. The results indicated DEX could induce cell viability decline in hFOB 1.19 cells, which was ameliorated by hsa_circ_0002060 knockdown. Consistently, DEX-induced cell apoptosis of hFOB 1.19 was ameliorated by hsa_circ_0002060 knockdown as well. As for the underlying mechanisms study, hsa_circ_0002060 was proved to regulate the viability of hFOB 1.19 cells through targeting miR-198-5p/Bax axis. Additionally, hsa_circ_0002060 knockdown alleviated ovariectomy-induced OP in a mouse model. Taken together, hsa_circ_0002060 knockdown alleviated the progression of OP by targeting miR-198-5p. Hsa_circ_0002060 might possibly be served as a therapeutic target for treating OP.
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http://dx.doi.org/10.1248/bpb.b20-00643DOI Listing
January 2021

ssp. Lactis 420 Mitigates Autoimmune Hepatitis Through Regulating Intestinal Barrier and Liver Immune Cells.

Front Immunol 2020 6;11:569104. Epub 2020 Oct 6.

Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause. Accumulating evidence shows that gut microbiota and intestinal barrier play significant roles in AIH thus the gut-liver axis has important clinical significance as a potential therapeutic target. In the present study, we found that ssp. lactis 420 (B420) significantly alleviated S100-induced experimental autoimmune hepatitis (EAH) and modulated the gut microbiota composition. While the analysis of clinical specimens revealed that the fecal SCFA quantities were decreased in AIH patients, and B420 increased the cecal SCFA quantities in EAH mice. Remarkably, B420 application improved intestinal barrier function through upregulation of tight junction proteins in both vitro and vivo experiments. Moreover, B420 decreased the serum endotoxin level and suppressed the RIP3 signaling pathway of liver macrophages in EAH mice thus regulated the proliferation of Th17 cells. Nevertheless, the inhibition effect of B420 on RIP3 signaling pathway was blunted studies. Together, our results showed that early intervention with B420 contributed to improve the liver immune homeostasis and liver injury in EAH mice, which might be partly due to the protection of intestinal barrier. Our study suggested the potential efficacy of probiotics application against AIH and the promising therapeutic strategies targeting gut-liver axis for AIH.
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http://dx.doi.org/10.3389/fimmu.2020.569104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573389PMC
May 2021