Publications by authors named "Bo Han"

628 Publications

Seeded 2D epitaxy of large-area single-crystal films of the van der Waals semiconductor 2H MoTe.

Science 2021 Apr;372(6538):195-200

State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-Optoelectronics, School of Physics, Peking University, Beijing 100871, China.

The integration of two-dimensional (2D) van der Waals semiconductors into silicon electronics technology will require the production of large-scale, uniform, and highly crystalline films. We report a route for synthesizing wafer-scale single-crystalline 2H molybdenum ditelluride (MoTe) semiconductors on an amorphous insulating substrate. In-plane 2D-epitaxy growth by tellurizing was triggered from a deliberately implanted single seed crystal. The resulting single-crystalline film completely covered a 2.5-centimeter wafer with excellent uniformity. The 2H MoTe 2D single-crystalline film can use itself as a template for further rapid epitaxy in a vertical manner. Transistor arrays fabricated with the as-prepared 2H MoTe single crystals exhibited high electrical performance, with excellent uniformity and 100% device yield.
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http://dx.doi.org/10.1126/science.abf5825DOI Listing
April 2021

MicroRNAs as crucial mediators in the pharmacological activities of triptolide (Review).

Exp Ther Med 2021 May 17;21(5):499. Epub 2021 Mar 17.

College of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, Shanxi 030619, P.R. China.

Triptolide is the main bioactive constituent isolated from the Chinese herb Hook F., which possesses a variety of pharmacological properties. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miRNAs are implicated in several intracellular processes, whereby their dysregulation contributes to pathogenesis of various diseases. Thus, miRNAs have great potential as biomarkers and therapeutic targets for diseases, and are implicated in drug treatment. Previous studies have reported that specific miRNAs are targeted, and their expression levels can be altered following exposure to triptolide. Thus, miRNAs are emerging as crucial mediators in the pharmacological activities of triptolide. The present review summarizes current literature on miRNAs as target molecules in the pharmacological activities of triptolide, including antitumor, anti-inflammatory, immunosuppressive, renal protective, cardioprotective, antiangiogenesis activities and multiorgan toxicity effects. In addition, the diverse signaling pathways involved are discussed to provide a comprehensive understanding of the underlying molecular mechanisms of triptolide in the regulation of target miRNAs.
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http://dx.doi.org/10.3892/etm.2021.9930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005665PMC
May 2021

Design, synthesis, and biological evaluation of nitroisoxazole-containing spiro[pyrrolidin-oxindole] derivatives as novel glutathione peroxidase 4/mouse double minute 2 dual inhibitors that inhibit breast adenocarcinoma cell proliferation.

Eur J Med Chem 2021 Mar 9;217:113359. Epub 2021 Mar 9.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address:

A series of highly active CF-containing 3'-(nitroisoxazole)spiro[pyrrolidin-3,2'-oxindoles] were synthesized and found to be novel glutathione peroxidase 4 (GPX4)/mouse double minute 2 (MDM2) dual inhibitors. Bioactive spirooxindole and isoxazole skeletons were combined, and the resulting compounds exhibited strong activities against both targets. In particular, compound 3d displayed excellent activity in the suppression of MDM2-mediated degradation of p53, as well as levels of GPX4, in MCF-7 breast cancer cells. Moreover, 3d also exhibited inhibitory effects on MDM2 and GPX4 in MCF-7 xenograft model to trigger ferroptotic and apoptotic cell death in in vivo experiments, which was consistent with the results of in vitro experiments.
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http://dx.doi.org/10.1016/j.ejmech.2021.113359DOI Listing
March 2021

Semiparametric estimation of the nonmixture cure model with auxiliary survival information.

Biometrics 2021 Mar 15. Epub 2021 Mar 15.

School of Mathematical Sciences, Dalian University of Technology, Liaoning, China.

With rapidly increasing data sources, statistical methods that make use of external information are gradually becoming popular tools in medical research. In this article, we efficiently synthesize the auxiliary survival information and propose a semiparametric estimation method for the combined empirical likelihood in the framework of the nonmixture cure model, to enhance inference about the associations between exposures and disease outcomes. The auxiliary survival probabilities from external sources are first summarized as unbiased estimation equations, which help produce more efficient estimates of the effects of interest and improve the prediction accuracy for the risk of the event. Then we develop a Bernstein-based sieve empirical likelihood method to estimate the parametric and nonparametric components simultaneously. Such an estimation procedure allows us to reduce the computation burden while preserving the shape constraint on the baseline distribution function. The resulting estimators for the true associations are strongly consistent and asymptotically normal. Instead of collecting substantial exposure data, the auxiliary survival information at multiple time points is incorporated, which further reduces the mean squared error of the estimators. This contributes to biomarker evaluation and treatment effect analysis within smaller studies. We show how to choose the number of auxiliary survival probabilities appropriately and provide a guideline for practical applications. Simulation studies demonstrate that the estimators enjoy large gains in efficiency. A melanoma dataset is analyzed for illustrating the methodology.
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http://dx.doi.org/10.1111/biom.13450DOI Listing
March 2021

Recent advances in the development of nanomedicines for the treatment of ischemic stroke.

Bioact Mater 2021 Sep 20;6(9):2854-2869. Epub 2021 Feb 20.

Shenzhen International Institute for Biomedical Research, 518116, Shenzhen, Guangdong, China.

Ischemic stroke is still a serious threat to human life and health, but there are few therapeutic options available to treat stroke because of limited blood-brain penetration. The development of nanotechnology may overcome some of the problems related to traditional drug development. In this review, we focus on the potential applications of nanotechnology in stroke. First, we will discuss the main molecular pathological mechanisms of ischemic stroke to develop a targeted strategy. Second, considering the important role of the blood-brain barrier in stroke treatment, we also delve mechanisms by which the blood-brain barrier protects the brain, and the reasons why the therapeutics must pass through the blood-brain barrier to achieve efficacy. Lastly, we provide a comprehensive review related to the application of nanomaterials to treat stroke, including liposomes, polymers, metal nanoparticles, carbon nanotubes, graphene, black phosphorus, hydrogels and dendrimers. To conclude, we will summarize the challenges and future prospects of nanomedicine-based stroke treatments.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905263PMC
September 2021

Fluorescence Sensing of Formaldehyde and Acetaldehyde Based on Responsive Inverse Opal Photonic Crystals: A Multiple-Application Detection Platform.

ACS Appl Mater Interfaces 2021 Mar 11;13(11):13792-13801. Epub 2021 Mar 11.

Key Laboratory of New Energy & New Functional Materials, Shaanxi Key Laboratory of Chemical Reaction Engineering, College of Chemistry and Chemical Engineering, Yan'an University, Yan'an, Shaanxi 716000, PR China.

Formaldehyde (FA) and acetaldehyde (AcH) used as common chemicals in many fields are carcinogenic. The presently reported detection methods usually need expensive instruments, professional technicians, and time-consuming processes, and the detection sensitivity still needs further improvement. Herein, we report a highly effective fluorescence (FL) sensing film for FA and AcH based on naphthalimide derivative-infiltrated responsive SiO inverse opal photonic crystals (PCs), establishing a practically multiple-application detection platform for FA and AcH in air, aquatic products, and living cells. Nucleophilic addition products between the amine group of the naphthalimide derivative and aldehydes emit strong FL at ∼550 nm, realizing selective FL detection for FA and AcH. The emitted FL can be enhanced remarkably because of the slow photon effect of PCs, in which the FL wavelength is located at the stopband edge of PCs. A highly sensitive detection for FA and AcH with limits of detection of 10.6 and 7.3 nM, respectively, is achieved, increasing 3 orders of magnitude compared with that in the solution system. Additionally, the interconnected three-dimensional microporous inverse opal structure endows the sensor with a rapid response within 1 min. Furthermore, the as-prepared PC sensor can be reused by simple washing in an acidic aqueous solution. The sensing system can be used as a FL multi-detection platform for FA and AcH in air, aqueous solution, and living cells. This FL sensing approach based on small organic molecule-functionalized PCs is universally available to develop various sensors for target analytes by designing new functional organic compounds.
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http://dx.doi.org/10.1021/acsami.0c22105DOI Listing
March 2021

Immunotherapy: A Potential Approach for High-Grade Spinal Cord Astrocytomas.

Front Immunol 2020 18;11:582828. Epub 2021 Feb 18.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Spinal cord astrocytomas (SCAs) account for 6-8% of all primary spinal cord tumors. For high-grade SCAs, the prognosis is often poor with conventional therapy, thus the urgent need for novel treatments to improve patient survival. Immunotherapy is a promising therapeutic strategy and has been used to treat cancer in recent years. Several clinical trials have evaluated immunotherapy for intracranial gliomas, providing evidence for immunotherapy-mediated ability to inhibit tumor growth. Given the unique microenvironment and molecular biology of the spinal cord, this review will offer new perspectives on moving toward the application of successful immunotherapy for SCAs based on the latest studies and literature. Furthermore, we will discuss the challenges associated with immunotherapy in SCAs, propose prospects for future research, and provide a periodic summary of the current state of immunotherapy for SCAs immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.582828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930372PMC
February 2021

Evodiamine alleviates lipopolysaccharide-induced pulmonary inflammation and fibrosis by activating apelin pathway.

Phytother Res 2021 Mar 3. Epub 2021 Mar 3.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Inflammation can cause a series of inflammatory lung disease, which seriously endangers human health. Pulmonary fibrosis is a kind of inflammatory disease with end-stage lung pathological changes. It has complicated and unknown pathogenesis and is still lack of effective therapeutic drugs. LPS-induced inflammation is a common feature of many infectious inflammations such as pneumonia, bacteremia, glomerulonephritis, etc. Evodiamine, one of the main components of Evodia rutaecarpa, is an alkaloid with excellent antiinflammatory effects. In this study, we evaluated the protective capacities of evodiamine on LPS-induced inflammatory damages in vitro and in vivo. MTT method, flow cytometry, immunofluorescence, and other methods were used for in vitro study to determine the protective capacities of evodiamine. The results suggest that evodiamine can protect murine macrophages from the LPS-nigericin-induced damages by (a) inhibiting cellular apoptosis, (b) inhibiting inflammatory cytokines releasing, and (c) activating the apelin pathway. We also used the exogenous apelin-13 peptide co-cultured with LPS-nigericin in RAW264.7 cells and found that apelin-13 contributes to protecting the effects of evodiamine. In vivo, the ELISA method and immunohistochemistry were used to examine inflammatory cytokines, apelin, and histological changes. BALB/c mice were exposed to LPS and subsequent administration of evodiamine (p.o.)for some time, the results of the alveolar lavage fluid and the tissue slices showed that evodiamine treatment alleviated the pulmonary inflammation and fibrosis, stimulated apelin expression and inhibited the inflammatory cytokines. These results provide a basis for the protective effect and mechanism of evodiamine in LPS-induced inflammation and suggest that it might be potential therapeutics in human pulmonary infections.
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http://dx.doi.org/10.1002/ptr.7062DOI Listing
March 2021

Effect of Notch1 on neural tube defects and neural stem cell differentiation induced by all‑trans retinoic acid.

Mol Med Rep 2021 Mar 21;23(3). Epub 2021 Jan 21.

Department of Pediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.

Neural tube defects (NTDs) are the most serious and common birth defects in the clinical setting. The Notch signaling pathway has been implicated in different processes of the embryonic neural stem cells (NSCs) during neural tube development. The aim of the present study was to investigate the expression pattern and function of Notch1 (N1) in all‑trans retinoic acid (atRA)‑induced NTDs and NSC differentiation. A mouse model of brain abnormality was established by administering 28 mg/kg atRA, and then brain development was examined using hematoxylin and eosin (H&E) staining. The N1 expression pattern was detected in the brain of mice embryos via immunohistochemistry and western blotting. NSCs were extracted from the fetal brain of C57 BL/6 embryos at 18.5 days of pregnancy. N1, Nestin, neurofilament (NF), glial fibrillary acidic protein (GFAP) and galactocerebroside (GALC) were identified using immunohistochemistry. Moreover, N1, presenilin 1 (PS1), Nestin, NF, GFAP and GALC were detected via western blotting at different time points in the NSCs with control media or atRA media. H&E staining identified that the embryonic brain treated with atRA was more developed compared with the control group. N1 was downregulated in the embryonic mouse brain between days 11 and 17 in the atRA‑treated group compared with the untreated group. The distribution of N1, Nestin, NF, GFAP and GALC was positively detected using immunofluorescence staining. Western blotting results demonstrated that there were significantly, synchronous decreased expression levels of N1 and PS1, but increased expression levels of NF, GFAP and GALC in NSCs treated with atRA compared with those observed in the controls (P<0.05). The results suggested that the N1 signaling pathway inhibited brain development and NSC differentiation. Collectively, it was found that atRA promoted mouse embryo brain development and the differentiation of NSCs by inhibiting the N1 pathway.
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http://dx.doi.org/10.3892/mmr.2021.11859DOI Listing
March 2021

Long noncoding RNA NONHSAT177112.1 aggravates inflammation and apoptosis in LPS-treated human cardiomyocytes.

Epigenomics 2021 03 1;13(6):411-422. Epub 2021 Mar 1.

Department of Midwifery, Taishan Vocational College of Nursing, Taian, Shandong 271000, China.

To explore the roles of lncRNA NONHSAT177112.1 in the inflammatory injury of human cardiomyocytes (HCMs) induced by lipopolysaccharide (LPS). The sublocalization of NONHSAT177112.1 was detected by FISH. HCMs were stimulated with LPS to induce inflammatory injury. NONHSAT177112.1 expression was detected by quantitative real-time PCR. Cell apoptosis and viability were detected by flow cytometry and CCK-8 assays. The expression of inflammatory cytokines and myocardial enzymes were detected by PCR and ELISA. NONHSAT177112.1 is expressed in the nucleus and cytoplasm. NONHSAT177112.1 showed dynamic expression that first increased and then decreased during LPS stimulation. NONHSAT177112.1 knockdown reversed the promotion effect of LPS on inflammatory injury. Conversely, NONHSAT177112.1 overexpression exerted the opposite effects. NONHSAT177112.1 aggravates inflammatory injury in LPS-treated HCMs.
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http://dx.doi.org/10.2217/epi-2020-0345DOI Listing
March 2021

The Feasibility of Assessing the Cortical Bone Trajectory Screw Placement Accuracy Using a Traditional Pedicle Screw Insertion Evaluation System.

Clin Spine Surg 2021 Mar;34(2):E112-E120

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University of China, Beijing, China.

Study Design: This was a retrospective observational study.

Objective: We aimed to characterize the feasibility of assessing the accuracy of cortical bone trajectory (CBT) screw placement in midline lumbar interbody fusion using a traditional pedicle screw insertion accuracy evaluation system based on computed tomography (CT).

Summary Of Background Data: Since Santoni and colleagues proposed CBT as an alternative approach for the treatment of lumbar degenerative disease, CBT has been biomechanically and clinically investigated in detail. The reported misplacement rate was 0%-12.5%. Therefore, these cortical screws may result in severe complications, such as nerve root, vascular, and spinal cord injuries. However, to the best of our knowledge, the accuracy of the current assessment system of cortical bone screw placement has not been described clearly.

Materials And Methods: Overall, 342 cortical screws of 69 consecutive patients with lumbar degenerative disease who underwent midline lumbar interbody fusion surgery in one surgeon's initial phase were examined retrospectively. A comprehensive and detailed pedicle screw accuracy classification and grading system was introduced in our study, including 5 types of misplacement: (1) medial and (2) lateral cortical bone perforation (MCP and LCP) of the corresponding pedicle, (3) anterior cortical bone perforation of the vertebral body, (4) endplate perforation, and (5) foraminal perforation (FP). The degree of interobserver and intraobserver agreement with regard to the screw positions based on CT were used as indicators of the reliability of the modified classification system. All patients were retrospectively assessed for screw placement-related complications throughout the entire treatment course to evaluate the relationship between the procedure adequacy and neurological symptoms.

Results: The interobserver and intraobserver agreements were substantial-to-almost perfect (κ=0.78 and 0.88, respectively) in distinguishing the acceptable-placed pedicle screws from those with partial or complete cortical perforation. In the MCP and LCP-the most common types of misplacement-the interobserver agreement was substantial (κ=0.70 and 0.76, respectively), and the intraobserver agreement was almost perfect (κ=0.85 and 0.89, respectively). In total, there are 7 (2.05%) MCP and 65 (19.01%) LCP screws. The screw placement-related complication rate is significantly higher in the MCP and FP groups than that in the LCP group.

Conclusions: Our study demonstrated that using a pedicle screw classification and grading system based on CT to assess the accuracy of CBT screw placement is feasible and practical. MCP and FP screws are more likely to cause neurological deficits with statistical significance, especially grade 2 MCP. We recommend inexperienced surgeons choose a lateral trajectory rather than a medial one if they cannot ensure accurate screw insertion.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001059DOI Listing
March 2021

Instance-Dependent Positive and Unlabeled Learning with Labeling Bias Estimation.

IEEE Trans Pattern Anal Mach Intell 2021 Feb 23;PP. Epub 2021 Feb 23.

This paper studies instance-dependent Positive and Unlabeled (PU) classification, where whether a positive example will be labeled (indicated by s) is not only related to the class label y, but also depends on the observation x. Therefore, the labeling probability on positive examples is not uniform as previous works assumed, but is biased to some simple or critical data points. To depict the above dependency relationship, a graphical model is built in this paper which further leads to a maximization problem on the induced likelihood function regarding P(s,y|x). By utilizing the well-known EM and Adam optimization techniques, the labeling probability of any positive example P(s=1|y=1,x) as well as the classifier induced by P(y|x) can be acquired. Theoretically, we prove that the critical solution always exists, and is locally unique for linear model if some sufficient conditions are met. Moreover, we upper bound the generalization error for both linear logistic and non-linear network instantiations of our algorithm. Empirically, we compare our method with state-of-the-art instance-independent and instance-dependent PU algorithms on a wide range of synthetic, benchmark and real-world datasets, and the experimental results firmly demonstrate the advantage of the proposed method over the existing PU approaches.
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http://dx.doi.org/10.1109/TPAMI.2021.3061456DOI Listing
February 2021

Differential Expression Profiles and Functional Analysis of Long Non-coding RNAs in Children With Dilated Cardiomyopathy.

Front Pediatr 2021 4;9:617298. Epub 2021 Feb 4.

Department of Pediatric Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions. The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data. There were 369 up-regulated lncRNAs identified in the DCM patients (fold change >2, < 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function. LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.
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http://dx.doi.org/10.3389/fped.2021.617298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891041PMC
February 2021

Risk Factors and Outcomes of Postprocedure Complete Left Bundle Branch Block After Transcatheter Device Closure of Perimembranous Ventricular Septal Defect.

Circ Cardiovasc Interv 2021 Feb 16;14(2):e009823. Epub 2021 Feb 16.

Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009823DOI Listing
February 2021

Klebsiella pneumoniae infection causes mitochondrial damage and dysfunction in bovine mammary epithelial cells.

Vet Res 2021 Feb 10;52(1):17. Epub 2021 Feb 10.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

Klebsiella pneumoniae, an important cause of bovine mastitis worldwide, is strongly pathogenic to bovine mammary epithelial cells (bMECs). Our objective was to determine the role of mitochondrial damage in the pathogenicity of K. pneumoniae on bMECs, by assessing several classical indicators of mitochondrial dysfunction, as well as differentially expressed genes (DEGs). Two K. pneumoniae strains (HLJ-D2 and HB-AF5), isolated from cows with clinical mastitis (CM), were used to infect bMECs (MAC-T line) cultured in vitro. In whole-transcriptome analysis of bMECs at 6 h post-infection (hpi), there were 3453 up-regulated and 3470 down-regulated genes for HLJ-D2, whereas for HB-AF5, there were 2891 up-regulated and 3278 down-regulated genes (P < 0.05). Based on GO term enrichment of differentially expressed genes (DEGs), relative to the controls, the primary categories altered in K. pneumoniae-infected bMECs included cellular macromolecule metabolism, metabolic process, binding, molecular function, etc. Infections increased (P < 0.05) malondialdehyde concentrations and formation of reactive oxygen species in bMECs. Additionally, both bacterial strains decreased (P < 0.05) total antioxidant capacity in bMECs at 6 and 12 hpi. Furthermore, infections decreased (P < 0.05) mitochondrial membrane potential and increased (P < 0.01) mitochondrial calcium concentrations. Finally, severe mitochondrial swelling and vacuolation, as well as mitochondrial rupture and cristae degeneration, were detected in infected bMECs. In conclusion, K. pneumoniae infections induced profound mitochondrial damage and dysfunction in bMECs; we inferred that this caused cellular damage and contributes to the pathogenesis of K. pneumoniae-induced CM in dairy cows.
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http://dx.doi.org/10.1186/s13567-021-00898-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876824PMC
February 2021

3D-printed drill guide template, a promising tool to improve pedicle screw placement accuracy in spinal deformity surgery: A systematic review and meta-analysis.

Eur Spine J 2021 Feb 8. Epub 2021 Feb 8.

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, GongTiNanLu 8#, Chaoyang District, Beijing, 100020, China.

Purpose: This study aimed to compare the pedicle screw placement accuracy and surgical outcomes between 3D-printed (3DP) drill guide template technique and freehand technique in spinal deformity surgery.

Methods: A comprehensive systematic literature search of databases (PubMed, Embase, Cochrane Library, and Web of Science) was conducted. The meta-analysis compared the pedicle screw placement accuracy and other important surgical outcomes between the two techniques.

Results: A total of seven studies were included in the meta-analysis, comprising 87 patients with 1384 pedicle screws placed by 3DP drill guide templates and 88 patients with 1392 pedicle screws placed by freehand technique. The meta-analysis results revealed that the 3DP template technique was significantly more accurate than the freehand technique to place pedicle screws and had a higher rate of excellently placed screws (OR 2.22, P < 0.001) and qualifiedly placed screws (OR 3.66, P < 0.001), and a lower rate of poorly placed screws (OR 0.23, P < 0.001). The mean placement time per screw (WMD-1.99, P < 0.05), total screw placement time (WMD-27.86, P < 0.001), and blood loss (WMD-104.58, P < 0.05) were significantly reduced in the 3DP template group compared with the freehand group. Moreover, there was no significant statistical difference between the two techniques in terms of the operation time and correction rate of main bend curve.

Conclusions: This study demonstrated that the 3DP drill guide template was a promising tool for assisting the pedicle screw placement in spinal deformity surgery and deserved further promotion.
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http://dx.doi.org/10.1007/s00586-021-06739-xDOI Listing
February 2021

Clonal evolution in liver cancer at single-cell and single-variant resolution.

J Hematol Oncol 2021 Feb 2;14(1):22. Epub 2021 Feb 2.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.
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http://dx.doi.org/10.1186/s13045-021-01036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852352PMC
February 2021

A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle.

J Anim Sci Biotechnol 2021 Feb 1;12(1):24. Epub 2021 Feb 1.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, China.

Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.

Results: Through re-sequencing the complete coding region, and 3000 bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001-0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G > A, g.146704373A > G, g.146704618A > G and g.146704699G > A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A > G and g.146704618A > G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).

Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.
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http://dx.doi.org/10.1186/s40104-020-00540-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849138PMC
February 2021

Millennials as organizational citizens: Conceptualization and measurement development.

J Soc Psychol 2021 Jan 26:1-20. Epub 2021 Jan 26.

Texas A&M University Commerce.

Despite existing scholarly progress in organizational citizenship behavior (OCB), prior research has predominantly investigated OCB using Baby Boomers and Generation Xers. As Millennials who possess different sets of workplace values and beliefs are entering the workforce, there is a need for conceptualizing OCB and developing an OCB scale suitable for Millennials. In this study, we conceptualize OCB in Millennials as voluntary behaviors that promote the prosperity of oneself, coworkers, the organization, and the community. Additionally, we employ exploratory factor analysis and identify a four-factor model of OCB, including empathetic responsiveness, role modeling, professional development, and social responsibility. We then conduct confirmatory factor analysis and construct a 13-item measurement scale for Millennial OCB. Finally, we assess and find evidence for the construct validity of the 13-item measurement scale. We conclude this study with an overview of theoretical and managerial implications.
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http://dx.doi.org/10.1080/00224545.2021.1874256DOI Listing
January 2021

Asymmetric organocatalysis: an enabling technology for medicinal chemistry.

Chem Soc Rev 2021 Feb;50(3):1522-1586

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. and Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.

The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds.
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http://dx.doi.org/10.1039/d0cs00196aDOI Listing
February 2021

Bacteriophages isolated from dairy farm mitigated Klebsiella pneumoniae-induced inflammation in bovine mammary epithelial cells cultured in vitro.

BMC Vet Res 2021 Jan 19;17(1):37. Epub 2021 Jan 19.

College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, 100193, Beijing, P. R. China.

Background: Klebsiella pneumoniae, an environmental pathogen causing mastitis in dairy cattle, is often resistant to antibiotics. K. pneumoniae was used as the host bacteria to support bacteriophage replication; 2 bacteriophages, CM8-1 and SJT-2 were isolated and considered to have therapeutic potential. In the present study, we determined the ability of these 2 bacteriophages to mitigate cytotoxicity, pathomorphological changes, inflammatory responses and apoptosis induced by K. pneumoniae (bacteriophage to K. pneumoniae MOI 1:10) in bovine mammary epithelial cells (bMECs) cultured in vitro.

Results: Bacteriophages reduced bacterial adhesion and invasion and cytotoxicity (lactate dehydrogenase release). Morphological changes in bMECs, including swelling, shrinkage, necrosis and hematoxylin and eosin staining of cytoplasm, were apparent 4 to 8 h after infection with K. pneumoniae, but each bacteriophage significantly suppressed damage and decreased TNF-α and IL-1β concentrations. K. pneumoniae enhanced mRNA expression of TLR4, NF-κB, TNF-α, IL-1β, IL-6, IL-8, caspase-3, caspase-9 and cyt-c in bMECs and increased apoptosis of bMECs, although these effects were mitigated by treatment with either bacteriophage for 8 h.

Conclusions: Bacteriophages CM8-1 and SJT-2 mitigated K. pneumoniae-induced inflammation in bMECs cultured in vitro. Therefore, the potential of these bacteriophages for treating mastitis in cows should be determined in clinical trials.
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http://dx.doi.org/10.1186/s12917-020-02738-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814619PMC
January 2021

RNA-Seq Whole Transcriptome Analysis of Bovine Mammary Epithelial Cells in Response to Intracellular .

Front Vet Sci 2020 7;7:642. Epub 2020 Dec 7.

College of Veterinary Medicine, China Agricultural University, Beijing, China.

(), a common mastitis pathogen widespread in the natural environment of dairy farms, is capable of invading mammary epithelial cells making treatment difficult. However, the mechanism of the response of bovine mammary epithelial cell to invasion remains elusive. In this study, transcriptomic analysis and bioinformatics tools were applied to explore the differentially expressed RNAs in bovine mammary epithelial cells (bMECs) between the control and -treated group. A total of 259 differentially expressed mRNAs (DEmRNAs), 27 differentially expressed microRNAs (DEmiRNAs), and 21 differentially expressed long non-coding RNAs (DElncRNAs) were found. These RNAs mainly enrich the inflammatory response, immune response, endocytosis, and cytokine-cytokine receptor interaction. qRT-PCR was used to analyze the quality of the RNA-seq results. In particular, to the defense mechanism of bovine mammary epithelial cells against intracellular , the PPAR signaling pathway and the genes (ACOX2, CROT, and NUDT12) were found to be up-regulated to promote the production of peroxisomes and ROS, DRAM1 expression was also up-regulated to facilitate the activation of autophagy, indicating that the above mechanisms were involved in the elimination of intracellular in bovine mammary epithelial cells.
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http://dx.doi.org/10.3389/fvets.2020.00642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793973PMC
December 2020

Highly Chemoselective [2+1] Annulation of α-Alkylidene Pyrazolones with α-Bromonitroalkenes: Synthesis of Pyrazolone-Based Vinylcyclopropanes and Computational Studies.

J Org Chem 2021 Feb 10;86(3):2582-2592. Epub 2021 Jan 10.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People's Republic of China.

A highly chemoselective [2+1] annulation of α-alkylidene pyrazolones with α-bromonitroalkenes has been achieved under mild conditions. α-Alkylidene pyrazolones were unprecedentedly used as a C1 synthon to participate in annulation reactions, providing access to diverse vinylcyclopropane-based pyrazolone products. In addition, a spectrum of pharmaceutically interesting pyrazole-fused pyranone oximes could be rapidly obtained through a [2+1] annulation/rearrangement sequential process. Computational studies disclosed the origin of the observed chemoselectivity of the [2+1] cycloaddition.
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http://dx.doi.org/10.1021/acs.joc.0c02674DOI Listing
February 2021

The treatment of the atrophic clavicular nonunion by double-plate fixation with autogenous cancellous bone graft: a prospective study.

J Orthop Surg Res 2021 Jan 7;16(1):22. Epub 2021 Jan 7.

Department of Orthopaedics, Beijing Chao-Yang Hospital, China Capital Medical University, Beijing, 100020, China.

Background: The objective of this study is to assess prospectively the effectiveness of double-plate fixation combined with autogenous cancellous bone graft in the treatment for the atrophic clavicular nonunion.

Methods: Between February 2013 and November 2017, a total of 12 patients with atrophic clavicular nonunion (mean age, 40.4 ± 9.0 years, range, 27-60 years) were treated by double-plate fixation with autogenous cancellous bone graft in our institute. The Constant Score System was used to evaluate the preoperative and final outcomes. The Short Form-36 (SF-36) outcome questionnaire was used to assess the final clinical results.

Results: All patients were followed-up, with the average follow-up of 34.7 ± 6.7 months (range, 24-48 months). The healing rate was 100% in our study. The mean time of bony union was 9 weeks (range, 8-10 weeks). One patient had a postoperative superficial infection, and the patient was cured by oral antibiotics and wound dressing. No implant-related complications (plate-screw loosening or breakage) were observed postoperatively. No vascular injury, neural impairment, or thoracic outlet syndrome was discovered preoperatively or postoperatively. There is a statistical significance between the preoperative and the postoperative constant scores (P < 0.05). All the patients were satisfied with their final clinical results by SF-36 outcome questionnaire. Average scores of the physical function and bodily pain components of the SF-36 were 94.2 ± 7.3 and 92.5 ± 5.8, respectively.

Conclusion: Our results presented that double-plate fixation with autogenous cancellous bone graft is an effective treatment for atrophic clavicular nonunion, especially for those with a significant bone defect.
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http://dx.doi.org/10.1186/s13018-020-02154-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792052PMC
January 2021

Differential Expression Profiles and Functional Prediction of Circular RNAs in Pediatric Dilated Cardiomyopathy.

Front Mol Biosci 2020 18;7:600170. Epub 2020 Dec 18.

Department of Pediatric Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers in various diseases. To assess the different expression levels of circRNAs in pediatric dilated cardiomyopathy (PDCM) and explore their biological and mechanistic significance, we used RNA microarrays to identify differentially expressed circRNAs between three children diagnosed with PDCM and three healthy age-matched volunteers. The biological function of circRNAs was assessed with a circRNA-microRNA (miRNA)-mRNA interaction network constructed from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 25 children with PDCM and 25 healthy volunteers. We identified 257 up-regulated (fold change ≤ 0.5, < 0.05) and 899 down-regulated (fold change ≥2, < 0.05) circRNAs in PDCM patients when compared to healthy volunteers. The qRT-PCR experiments confirmed has_circ_0067735 down-regulation (0.45-fold, < 0.001), has_circ_0070186 up-regulation (2.82-fold, < 0.001), and has_circ_0069972 down-regulation (0.50-fold, < 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.
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http://dx.doi.org/10.3389/fmolb.2020.600170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775584PMC
December 2020

BTF3 promotes stemness and inhibits TypeⅠInterferon signaling pathway in triple-negative breast cancer.

Biochem Biophys Res Commun 2021 Jan 28;537:22-28. Epub 2020 Dec 28.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, Shandong University, School of Basic Medical Sciences, 250012, Jinan, China; Department of Pathology, Shandong University Qilu Hospital, 250012, Jinan, China. Electronic address:

Triple-negative breast cancer (TNBC) is a major challenge in clinical practice due to its aggressiveness and lack of targeted treatment. Cancer stem-like traits contribute to tumorigenesis and immune privilege of TNBC. However, the relationship of stemness and immunosurveillance remains unclear. Here, we demonstrate that BTF3 expression is related with stem-like properties in TNBC cells. BTF3 modulates stemness, migration and proliferation of TNBC in vitro. Bioinformatics analysis revealed that interferon signaling pathways and IRF7, both of which participate in the immune escape of TNBC, are closely related to BTF3 in TNBC cells. Knockdown of BTF3 activates IRF7 expression through increased degradation of BMI1, a protein that can represses IRF7 transcription by directly binding to its promotor region. BTF3 links stem-like traits and the interferon signaling pathway, revealing the potential connection of stemness and immunomodulation in TNBC. Clinically, we suggest that BTF3 is predictive of poor prognosis in patients with TNBC. Together, our findings highlight an important role of BTF3 in regulating the progression of TNBC cells.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.060DOI Listing
January 2021

Bacteriophage has beneficial effects in a murine model of Klebsiella pneumoniae mastitis.

J Dairy Sci 2021 Mar 25;104(3):3474-3484. Epub 2020 Dec 25.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China. Electronic address:

Bovine mastitis caused by Klebsiella pneumoniae is usually treated with antibiotics, thereby potentially increasing antimicrobial resistance. The objective of this study was to evaluate efficacy of a bacteriophage, isolated from dairy farm wastewater, as a treatment for a murine model of K. pneumoniae mastitis. A lytic bacteriophage CM8-1 was isolated, morphological and biological characteristics were assessed with transmission electron microscopy and double-layer plate, and its genome was sequenced and analyzed. Furthermore, effectiveness of this bacteriophage for treatment of a murine model of K. pneumoniae mastitis was evaluated based on the following mammary gland characteristics: morphological changes; number of K. pneumoniae; and mRNA and protein expression of pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-8. Bacteriophage CM8-1 had an incubation period of 30 min and a burst time of 20 min. Its viability and adsorption were stable at 30 to 50°C, but decreased significantly at >60°C, with no significant change in viability or infectivity at pH 6 to 10. In a murine model of K. pneumoniae mastitis, injecting bacteriophage CM8-1 into the mammary gland 2 h after inoculation with K. pneumoniae resulted in reductions in bacterial counts in the murine mammary gland, improvements in mammary gland tissue morphology, and reductions in mRNA and protein expression of pro-inflammatory factors. Bacteriophage CM8-1 had stable biological characteristics and suppressed K. pneumoniae mastitis when injected into the mammary gland 2 h latera in mice bacterial inoculation.
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http://dx.doi.org/10.3168/jds.2020-19094DOI Listing
March 2021

Stereoselective synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactam through the organocatalytic cascade reaction of 3-((2,2,2-trifluoroethyl)amino)indolin-2-one.

Org Biomol Chem 2021 01;19(2):467-475

School of Basic Medical Sciences, School of Pharmacy, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Newly designed 3-((2,2,2-trifluoroethyl)amino)indolin-2-ones were used for the facile synthesis of chiral fluoroalkyl-containing 3,2'-spirooxindole γ-lactam products. The secondary amine-catalysed Michael/hemiaminalization cascade reaction of 3-((2,2,2-trifluoroethyl)amino)indolin-2-one with α,β-unsaturated aldehydes followed by oxidation can easily produce the desired products in high yields (up to 86%) with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >95 : 5 dr).
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http://dx.doi.org/10.1039/d0ob02166kDOI Listing
January 2021

Reconstruction of parotid duct defect with autologous vein graft and vascular coupler after buccal mucosa cancer resection.

J Stomatol Oral Maxillofac Surg 2020 Dec 14. Epub 2020 Dec 14.

Department of Head and Neck Oncology, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, 610041 Chengdu, China. Electronic address:

The distal end of parotid duct is often inevitably resected en-block with the buccal mucosa cancer to obtain safety margin and prevent local recurrence. Ligation of duct frequently causes complications like cheek swelling, fistula and gland function loss. The authors describe a novel procedure of combined use of autologous vein graft and vascular coupler to reconstruct the parotid duct defect for buccal mucosa cancer patients who undergo radical neck dissection and free-flap reconstruction, no lumen-stent or cannula is needed. Case examples are shown to illustrate the operative details and different outcomes for two kinds of orifice site choices. Key factors for success include the proper use of Coupler device, right choice of new orifice location and maintenance of lumen patency. For buccal mucosa cancer patients, this novel method for parotid duct reconstruction could effectively reduce postoperative complications and preserve the parotid gland function.
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http://dx.doi.org/10.1016/j.jormas.2020.12.002DOI Listing
December 2020

Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21.

J Nutr Biochem 2021 Mar 14;89:108563. Epub 2020 Dec 14.

Cordoba-Nimni Tissue Engineering and Drug Discovery Lab, Department of Surgery, University of Southern California, Los Angeles, California.

Asthma is characterized by chronic inflammation and tissue remodeling of the airways. Remodeling is resistant to pharmaceutical therapies. This study investigated the effect of zinc salicylate-methylsulfonylmethane (Zn-Sal-MSM) compared to zinc salicylate (Zn-Sal), or sodium salicylate (Na-Sal), or zinc chloride (ZnCl) on remodeling parameters of human airway smooth muscle cells (ASMC). Human ASMC obtained from asthma patients (n=7) and non-asthma controls (n=7) were treated with one of the reagents. Cell proliferation and viability was determined by direct cell counts and MTT assay. The expression of and phosphorylation proteins was determined by Western-blotting, ELISA, immunofluorescence, and mass spectrometry. Extracellular matrix deposition by ELISA. Zn-Sal-MSM, Zn-Sal and Na-Sal (0.1-100 µg/mL) significantly reduced PDGF-BB-induced proliferation in a concentration dependent manner, while ZnCl was toxic. The reduced proliferation correlated with increased expression of the cell cycle inhibitor p21, and reduced activity of Akt, p70S6K, and Erk1/2. Zn-Sal-MSM, Zn-Sal, but not Na-Sal reduced the deposition of fibronectin and collagen type-I. Furthermore, Zn-Sal-MSM reduced the mitochondria specific COX4 expression. Mass spectrometry indicated that Zn-Sal-MSM modified the expression of several signaling proteins and zinc-dependent enzymes. In conclusion, Zn-Sal-MSM and Zn-Sal potentially prevent airway wall remodeling in asthma by inhibition of both the Erk1/2 and mTOR signaling pathways.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108563DOI Listing
March 2021