Publications by authors named "Xinyi Chen"

165 Publications

Senkyunolide H protects PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.

J Ethnopharmacol 2021 Sep 17;282:114659. Epub 2021 Sep 17.

Department of General Practice, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, China. Electronic address:

Ethnopharmacological Relevance: Senkyunolide H (SNH) is a bioactive phthalide isolated from Ligusticum chuanxiong Hort rhizome and was reported to have multiple pharmacological effects.

Aim Of The Study: The study was performed to verify the potency of SNH protecting PC12 cells from oxygen glucose deprivation/reperfusion (OGD/R)-induced injury and to elucidate the underlying mechanisms.

Materials And Methods: OGD/R model was established in PC12 cells and the cell viability was measured by MTT assay. The cell morphology was observed using scanning electron microscope (SEM). The potential targets of SNH and related targets of OGD/R were screened, and a merged protein-protein interaction (PPI) network of SNH and OGD/R was constructed based on the network pharmacology analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway analysis. Intracellular cAMP level and the protein expression levels were measured to elucidate the underlying mechanisms.

Results: SNH pretreatment protected PC12 cells against OGD/R-induced cell death. SNH also significantly protected the cell protrusion. A merged PPI network was constructed and the shared candidate targets significantly enriched in cAMP signaling pathway. The level of intracellular cAMP and the protein level of p-CREB, p-AKT, p-PDK1 and PKA protein were up-regulated after the treatment of SNH compared with OGD/R modeling.

Conclusions: The present study indicated that SNH protected PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1016/j.jep.2021.114659DOI Listing
September 2021

Effect of SMILE-derived decellularized lenticules as an adhesion barrier in a rabbit model of glaucoma filtration surgery.

BMC Ophthalmol 2021 Sep 9;21(1):329. Epub 2021 Sep 9.

Eye Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticules on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery.

Methods: Trabeculectomy was performed on both eyes of New Zealand rabbits. A decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (the decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (the control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery.

Results: Decellularized lenticules significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. The histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group.

Conclusions: Decellularized lenticules can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and they may represent a novel antifibrotic agent for trabeculectomy.
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http://dx.doi.org/10.1186/s12886-021-02090-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431885PMC
September 2021

Molecular Characterization of Advanced Colorectal Cancer Using Serum Proteomics and Metabolomics.

Front Mol Biosci 2021 27;8:687229. Epub 2021 Jul 27.

Jiangxi Cancer Hospital, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.

Colorectal cancer (CRC) is a growing public health concern due to its high mortality rate. Currently, there is a lack of valid diagnostic biomarkers and few therapeutic strategies are available for CRC treatment, especially for advanced CRC whose underlying pathogenic mechanisms remain poorly understood. In the present study, we investigated the serum samples from 20 patients with stage III or IV advanced CRC using data-independent acquisition (DIA)-based proteomics and ultra-performance liquid chromatography coupled to time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS) metabolomics techniques. Overall, 551 proteins and 719 metabolites were identified. Hierarchical clustering analysis revealed that the serum proteomes of advanced CRC are more diversified than the metabolomes. Ten biochemical pathways associated with cancer cell metabolism were enriched in the detected proteins and metabolites, including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, etc. A protein-protein interaction network in advanced CRC serum was constructed with 80 proteins and 21 related metabolites. Correlation analysis revealed conserved roles of lipids and lipid-like molecules in a regulatory network of advanced CRC. Three metabolites (hydroquinone, leucenol and sphingomyelin) and two proteins (coagulation factor XIII A chain and plasma kallikrein) were selected to be potential biomarkers for advanced CRC, which are positively and significantly correlated with CEA and/or CA 19-9. Altogether, the results expanded our understanding of the physiopathology of advanced CRC and discovered novel potential biomarkers for further validation and application to improve the diagnosis and monitoring of advanced CRC.
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http://dx.doi.org/10.3389/fmolb.2021.687229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353147PMC
July 2021

Identification and attribute analysis of key stakeholders who influence multidrug-resistant tuberculosis prevention and control in China.

Infect Dis Poverty 2021 Aug 12;10(1):108. Epub 2021 Aug 12.

Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.

Background: There could be various stakeholders who influencing multidrug-resistant tuberculosis (MDR-TB) policy development and implementation, yet their attributes and roles remain unclear in practice. This study aimed to identify key stakeholders in the process of policy-making for MDR-TB control and prevention and to analyse the attributes and relationships of the stakeholders, providing evidence for further policy research on MDR-TB control.

Methods: This study was conducted from October 2018 to March 2019 and applied the stakeholder analysis guidelines and domestic stakeholder analysis. An initial candidate stakeholder list was developed by policy scanning. Ten experts were invited to identify these candidate stakeholders. The major attribute of these stakeholders were analysed using the Michell scoring method. Based on these results, the intertwined relationships among groups of stakeholders were analysed and mapped through a systematic scan of the policy and literature on MDR-TB control, as well as information obtained from the interviews.

Results: A list of 21 types of candidate stakeholders was developed after a literature review and policy scanning, of which 11 received 100% approval. After expert evaluation and identification (the total expert authority was 0.80), 19 categories of stakeholders were approved and included in the stakeholder analysis. We categorized all of the stakeholders into three groups: (i) definitive stakeholders who are mainly involved in administrative departments and the Provincial Center for Disease Control and Prevention (CDC); (ii) expectant stakeholders who are mainly involved with MDR-TB patients, clinical departments of TB hospitals at different levels, community health care facilities, prefectural CDC and charity organizations; and (iii) latent stakeholders who mainly involved family members and neighbours of MDR-TB patients and TB related products manufacturers. Government departments and higher-level CDCs have strong decision-making power in developing MDR-TB control policies whereas the recommendations from service providers and the concerns of patients should be considered.

Conclusions: The MDR-TB prevention system was a multistakeholder cooperation system that was mainly led by government stakeholders. Enhancing communications with front-line service providers and patients on their unmet needs and evidence-based suggestions would highly benefit policy-making of MDR-TB prevention and control.
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http://dx.doi.org/10.1186/s40249-021-00892-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359086PMC
August 2021

The Encounter of Biomolecules in Metal-Organic Framework Micro/Nano Reactors.

ACS Appl Mater Interfaces 2021 Aug 9. Epub 2021 Aug 9.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, P.R. China.

In nature, biochemical reactions often take place in confined spaces, as typically exemplified by cells. As numerous cellular reactors can be integrated to maintain the living system, researchers have made constant efforts to construct cell-like structures for achieving similar transformations in vitro. Micro/nano reactors engineered by polymers and colloids are becoming popular and being applied in many fields, especially there has been an increasing trend toward constructing metal-organic framework (MOF) micro/nano reactors with the thriving of MOF nanotechnologies. Because of the uniform pores of MOFs, the transmission of substances can be regulated more accurately. Along with properties of large specific surface area, functional diversity and precise control of the particle size, MOFs are also ideal platforms for building distinct microenvironments for biological substances. Compared with traditional polymersomes and colloidosomes, the unique characteristics of MOFs render them potent micro/nano reactor shell materials, mimicking cells for applications in enzymatic catalysis, sensing, nanotherapy, vaccine, biodegradation, etc. This review highlights recent signs of progress on the design of MOF micro/nano reactors and their applications in biology, discusses the existing problems, and prospects their promising properties for smarter multifunctional applications.
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http://dx.doi.org/10.1021/acsami.1c09660DOI Listing
August 2021

Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer.

J Clin Oncol 2021 Sep 1;39(26):2926-2937. Epub 2021 Jul 1.

Department of Medicine, Carbone Cancer Center, University of Wisconsin, Madison, WI.

Purpose: Nearly all men with prostate cancer treated with androgen receptor (AR) signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including constitutive activation of the AR pathway, driven by AR genomic structural alterations, expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI resistance mechanisms is critical for optimizing therapy.

Materials And Methods: A novel liquid biopsy technology was used to collect mRNA from circulating tumor cells (CTCs) to measure expression of AR-Vs, AR targets, and neuroendocrine prostate cancer markers. An institutional review board-approved prospective cohort (N = 99) was used to identify patterns of gene expression. Two prospective multicenter phase II clinical trials of ARSIs for men with castration-resistant prostate cancer (ClinicalTrials.gov: NCT01942837 [enzalutamide, N = 21] and NCT02025010 [abiraterone, N = 27]) were used to further validate these findings.

Results: Hierarchical clustering of CTC transcripts identified two distinct clusters. Cluster 2 (C2) exhibited increased expression of AR-regulated genes and was associated with worse overall survival (median 8.6 22.4 months; < .01; hazard ratio [HR] = 3.45 [1.9 to 6.14]). In multivariable analysis, C2 was prognostic independent of other clinicopathologic variables. AR-V status was not significant when accounting for C2. Upon further validation in pooled multicenter phase II trials, C2 was associated with worse overall survival (15.2 months not reached; < .01; HR = 8.43 [2.74 to 25.92]), prostate-specific antigen progression-free survival (3.6 12 months; < .01; HR = 4.64 [1.53 to 14.11]), and radiographic progression-free survival (2.7 40.6 months; < .01; HR = 4.64 [1.82 to 17.41]).

Conclusion: We demonstrate that a transcriptional profile detectable in CTCs obtained from liquid biopsies can serve as an independent prognostic marker beyond AR-V7 in patients with metastatic prostate cancer and can be used to identify the emergence of multiple ARSI resistance mechanisms. This is currently being investigated in additional prospective trials.
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http://dx.doi.org/10.1200/JCO.21.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425833PMC
September 2021

The impact of caries status on supragingival plaque and salivary microbiome in children with mixed dentition: a cross-sectional survey.

BMC Oral Health 2021 06 25;21(1):319. Epub 2021 Jun 25.

Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China.

Background: Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for caries development in first permanent molar (FPM); nevertheless, to the best of our knowledge, there are no reports on the effects of deciduous teeth caries on the microbiome of healthy FPM. Additionally, it remains unclear whether saliva can be used instead of supragingival plaque for caries microbial studies. Therefore, we aimed to elucidate this issue, and to characterize and compare the oral microbiome of healthy FPMs in children with different caries statuses and that from children with and without caries in a similar microhabitat, by PacBio sequencing. Currently, few studies have investigated the oral microbiome of children using this technique.

Methods: Thirty children (aged 7-9 years) with mixed dentition were enrolled; 15 had dental caries, and 15 did not. Supragingival plaques of deciduous molars and maxillary FPMs, and non-stimulating saliva samples were collected. DNA was extracted and the v1-v9 regions of 16S rRNA were amplified. Subsequently, PacBio sequencing and bioinformatic analyses were performed for microbiome identification.

Results: The microbial alpha diversity of the saliva samples was lower than that of the supragingival plaque (p < 0.05); however, no differences were detected between deciduous teeth and FPMs (p > 0.05). In addition, the alpha and beta diversity of children with and without caries was also similar (p > 0.05). Nonmetric multidimensional scaling and Adonis analyses indicated that the microbial structure of salivary and supragingival plaque samples differ (p < 0.05). Further analysis of deciduous teeth plaque showed that Streptococcus mutans, Propionibacterium acidifaciens, and Veillonella dispar were more abundant in children with caries than in those without (p < 0.05); while in FPMs plaque, Selenomonas noxia was more abundant in healthy children (p < 0.05). No differences in microorganisms abundance were found in the saliva subgroups (p > 0.05).

Conclusion: We have determined that supragingival plaque was the best candidate for studying carious microbiome. Furthermore, S. mutans, V. dispar, and P. acidifaciens were highly associated with deciduous teeth caries. S. noxia may be associated with the abiding health of FPM; however, this requires additional studies.
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http://dx.doi.org/10.1186/s12903-021-01683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229229PMC
June 2021

Do biochar and polyacrylamide have synergistic effect on net denitrification and ammonia volatilization in saline soils?

Environ Sci Pollut Res Int 2021 Jun 21. Epub 2021 Jun 21.

Key Laboratory of Soil and Sustainable Agriculture, Changshu National Agro-Ecosystem Observation and Research Station, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Salt-affected soils have poor structure and physicochemical properties, which affect soil nitrogen cycling process closely related to the environment, such as denitrification and ammonia volatilization. Biochar and polyacrylamide (PAM) have been widely used as soil amendments to improve soil physicochemical properties. However, how they affect denitrification and ammonia volatilization in saline soils is unclear. In this study, the denitrification and ammonia volatilization rates were measured in a saline soil field ameliorated with three biochar application rates (0%, 2%, and 5%, w/w) and three PAM application rates (0‰, 0.4‰, and 1‰, w/w) over 3 years. The results showed that denitrification rates decreased by 23.63-39.60% with biochar application, whereas ammonia volatilization rates increased by 9.82-25.58%. The denitrification and ammonia volatilization rates decreased by 9.87-29.08% and 11.39-19.42%, respectively, following PAM addition. However, there was no significant synergistic effect of biochar and PAM amendments on the denitrification and ammonia volatilization rates. The addition of biochar mainly reduced the denitrification rate by regulating the dissolved oxygen and electrical conductivity of overlying water and absorbing soil nitrate nitrogen. Meanwhile, biochar application increased pH and stimulated the transfer of NH-N from soil to overlying water, thus increasing NH volatilization rates. Hence, there was a tradeoff between denitrification and NH volatilization in the saline soils induced by biochar application. PAM reduced the denitrification rate by increasing the infiltration inorganic nitrogen and slowing the conversion of ammonium to nitrate. Moreover, PAM reduced the concentration of NH-N in the overlying water through absorbing soil ammonium and inhibiting urea hydrolysis, thereby decreasing NH volatilization rate.
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http://dx.doi.org/10.1007/s11356-021-14886-3DOI Listing
June 2021

Persistent Discrimination of TB in Southeastern China: Results from Four Repeated Population-Based Surveys During the Period of 2006-2018.

Risk Manag Healthc Policy 2021 3;14:2333-2344. Epub 2021 Jun 3.

Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China.

Objective: To analyze the changes in discriminatory attitudes and isolated behaviors of the public toward tuberculosis (TB) in the Zhejiang Province and to determine the associated factors with TB discrimination.

Methods: Data were obtained from four cross-sectional population-based investigations from 2006 to 2018. A total of 26,246 respondents were interviewed using unified questionnaires that measured knowledge, attitudes, and behaviors regarding TB. The changes in public attitudes and behaviors towards TB over time were analyzed. The effect of socio-demographic factors and the level of TB awareness on TB discriminatory attitudes and isolated behaviors were evaluated.

Results: The results of these four cross-sectional studies found that TB discrimination had not changed much over the decade. Overall, discriminatory attitudes were present in 63.5% of the respondents who knew about TB (81.2%). Nearly 31.2% of those who reported being surrounded by people with TB (5.8%) showed isolated behaviors. Older respondents, those with a low education level, and farmers were prone to having discriminatory attitudes or behaviors. Those aware of the infectiousness and transmission routes of TB, and those who felt that TB was serious were more likely to discriminate against TB ( < 0.001). Those aware that TB can be cured were non-discriminatory (aOR = 0.77, 95% CI: 0.72-0.82).

Conclusion: Discriminatory attitudes and isolated behaviors toward TB have not changed significantly in southeastern China over the survey years, and persistent discrimination against TB still exists among the public. The multiple causes of discrimination cannot be addressed through basic health education. Tailor-made strategies, relevant policy measures, and an enabling social environment for TB are urgently required.
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http://dx.doi.org/10.2147/RMHP.S311869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184293PMC
June 2021

Toxicity remission of PAEs on multireceptors after molecular modification through a 3D-QSAR pharmacophore model coupled with a gray interconnect degree method.

Authors:
Xinyi Chen Yu Li

Turk J Chem 2021 28;45(2):307-322. Epub 2021 Apr 28.

MOE Key Laboratory of Resource and Environmental System Optimization, Ministry of Education,North China Electric Power University, Beijing China.

In the proposed model, the gray interconnect degree method was employed to process the acute toxicity values of phthalate acid esters (PAEs) to green algae, daphnia, mysid, and fish (predicted by EPI Suite software) and to obtain the comprehensive characterization value of the multireceptor toxicity effect (MTE) of PAEs. The 3D-QSAR pharmacophore model indicated that hydrophobic groups significantly affected the MTE of PAEs. Based on this, 16 PAEs derivative molecules with significantly decreased comprehensive characterization value (more than 10%) of the toxic effects of multireceptors were designed. Among them, 13 PAEs derivative molecules reduced the toxicity values (predicted by the EPI Suite software) of four receptor organisms to varying degrees. Finally, two derivative molecules from PAEs were screened and could exist stably in the environment. The derivative molecule's reduced toxicity to the receptor was obtained through molecular docking methods and simulated the PAEs' primary metabolic response pathways. The above research results break through the pharmacophore model's limitation of only being suitable for the single effect of pollutants. Its application provides a new theoretical verification basis for expanding the multieffect pharmacophore model.
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http://dx.doi.org/10.3906/kim-2008-38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164199PMC
April 2021

Risk Factors for Mucosal Involvement in Bullous Pemphigoid and the Possible Mechanism: A Review.

Front Med (Lausanne) 2021 20;8:680871. Epub 2021 May 20.

Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Bullous pemphigoid (BP) is the most common type of autoimmune bullous disease and is characterized by the presence of circulating anti-BP180 and/or anti-BP230 autoantibodies. Patients with BP often present with tense blisters and erythema, mainly on the trunk and limbs, but a few patients also have mucosal involvement. In this article, we discuss the fact that BP patients with mucosal involvement tend to have more serious conditions and their disease is more difficult to control. Potential risk factors for mucous involvement include earlier age at onset, drugs such as dipeptidyl peptidase-4 inhibitors, cancer, and blood/serum biomarkers, including lower eosinophil count, higher erythrocyte sedimentation rate, IgG autoantibodies against both the NH- and COOH-termini of BP180, and the absence of anti-BP230 antibodies. IgA and C3 deposition at the dermo-epidermal junction may also be present. Understanding these risk factors may benefit earlier diagnosis of these patients and promote the development of novel treatments. What's more, it's helpful in deeper understanding of BP development and the relationship between BP and mucous membrane pemphigoid (MMP).
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http://dx.doi.org/10.3389/fmed.2021.680871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172594PMC
May 2021

Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner.

Commun Biol 2021 06 2;4(1):656. Epub 2021 Jun 2.

Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Pharmacological reversal of brain aging is a long-sought yet challenging strategy for the prevention and treatment of age-related neurodegeneration, due to the diverse cell types and complex cellular pathways impacted by the aging process. Here, we report the genome-wide reversal of transcriptomic aging signatures in multiple major brain cell types, including glial and mural cells, by systemic glucagon-like peptide-1 receptor (GLP-1R) agonist (GLP-1RA) treatment. The age-related expression changes reversed by GLP-1RA encompass both shared and cell type-specific functional pathways that are implicated in aging and neurodegeneration. Concomitantly, Alzheimer's disease (AD)-associated transcriptomic signature in microglia that arises from aging is reduced. These results show the feasibility of reversing brain aging by pharmacological means, provide mechanistic insights into the neurological benefits of GLP-1RAs, and imply that GLP-1R agonism may be a generally applicable pharmacological intervention for patients at risk of age-related neurodegeneration.
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http://dx.doi.org/10.1038/s42003-021-02208-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172568PMC
June 2021

The hemostatic mechanism of "Treated the Spleen" therapy on immune thrombocytopenia based on the characteristics of vasoactive factors.

Ann Palliat Med 2021 Apr;10(4):4612-4622

Department of Hematology, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Background: To explore the effect mechanism of "treat the spleen" therapy on immune thrombocytopenia (ITP) based on the characteristics of vasoactive factors.

Methods: The ITP mice model was established by passive immunomodeling. 120 successfully modeled BALB/c mice were randomly divided into 6 groups: normal group, model group, prednisone group, Guipi Decoction group, Jianpi Yiqi group, and Jianpi Shexue group. These mice were treated with medicine for 16 days. After treatment, the platelet (PLT) counts and the degree of bleeding were evaluated, and the serum ET-1, NO, NOS3, TXA2, PGI2, vWF, VCAM-1, and TM contents of the model mice were detected by enzyme-linked immunosorbent assay (ELISA).

Results: The PLT counts in peripheral blood of mice in each experimental group significantly decreased compared with that in the normal group (P<0.01). On the 8th day after commencing administration, compared with the model group, PLT counts of mice in each experimental group significantly increased (P<0.01). Before administration, all groups had different bleeding tendencies except for the normal group. On the 6th and 8th day of drug intervention, compared with the model group, the bleeding grade of treated groups was significantly decreased (P<0.01). The values of ET-1, vWF, and VCAM-1 in each experimental group significantly decreased compared with that in the normal group, while the TXA2 values were up-regulated compared with that in the normal and model groups (P<0.01). The values of NO and TM in each experimental group significantly decreased compared with that in the normal group (P<0.05). In addition to the Guipi Decoction group, the NOS3 values in each group were significantly decreased compared with that in the normal group (P<0.05). The PGI2 values of the "treat the spleen" groups were significantly decreased compared to the normal group (P<0.01).

Conclusions: In addition to increasing the PLT counts in peripheral blood of ITP model mice to achieve a hemostatic effect, the "treat the spleen" recipes up-regulated the levels of TXA2 and VCAM-1, while down-regulating the levels of PGI2 and TM. Therefore, balancing the procoagulant and anticoagulant factors might be one of the effective mechanisms of hemostasis.
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http://dx.doi.org/10.21037/apm-21-765DOI Listing
April 2021

Enhanced Recombinant Protein Production Under Special Environmental Stress.

Front Microbiol 2021 15;12:630814. Epub 2021 Apr 15.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China.

Regardless of bacteria or eukaryotic microorganism hosts, improving their ability to express heterologous proteins is always a goal worthy of elaborate study. In addition to traditional methods including intracellular synthesis process regulation and extracellular environment optimization, some special or extreme conditions can also be employed to create an enhancing effect on heterologous protein production. In this review, we summarize some extreme environmental factors used for the improvement of heterologous protein expression, including low temperature, hypoxia, microgravity and high osmolality. The applications of these strategies are elaborated with examples of well-documented studies. We also demonstrated the confirmed or hypothetical mechanisms of environment stress affecting the host behaviors. In addition, multi-omics techniques driving the stress-responsive research for construction of efficient microbial cell factories are also prospected at the end.
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http://dx.doi.org/10.3389/fmicb.2021.630814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084102PMC
April 2021

GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, 61231, Germany;

G protein-coupled receptor 182 (GPR182) has been shown to be expressed in endothelial cells; however, its ligand and physiological role has remained elusive. We found GPR182 to be expressed in microvascular and lymphatic endothelial cells of most organs and to bind with nanomolar affinity the chemokines CXCL10, CXCL12, and CXCL13. In contrast to conventional chemokine receptors, binding of chemokines to GPR182 did not induce typical downstream signaling processes, including G- and G-mediated signaling or β-arrestin recruitment. GPR182 showed relatively high constitutive activity in regard to β-arrestin recruitment and rapidly internalized in a ligand-independent manner. In constitutive GPR182-deficient mice, as well as after induced endothelium-specific loss of GPR182, we found significant increases in the plasma levels of CXCL10, CXCL12, and CXCL13. Global and induced endothelium-specific GPR182-deficient mice showed a significant decrease in hematopoietic stem cells in the bone marrow as well as increased colony-forming units of hematopoietic progenitors in the blood and the spleen. Our data show that GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, which is involved in the regulation of hematopoietic stem cell homeostasis.
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http://dx.doi.org/10.1073/pnas.2021596118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092405PMC
April 2021

Developing a novel strategy for COPD therapy by targeting Nrf2 and metabolism reprogramming simultaneously.

Free Radic Biol Med 2021 06 1;169:436-445. Epub 2021 Apr 1.

Medical Imaging. the First Affiliated Hospital of Xi'an Jiaotong University. 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China. Electronic address:

Chronic obstructive pulmonary disease (COPD) is estimated to be the sixth major cause of disability, and the third main cause of death in the world by 2020. Although both inflammation and oxidative stress are well known to be the key predisposing factors in the pathogenesis of COPD, other elements, including metabolism, may also contribute to the exacerbation of the disease. However, the therapeutic approach which alters metabolism against COPD has yet been fully developed. Therefore, here we provide a novel therapeutic strategy for COPD patients. We first screened out the known nuclear factor erythroid-2-related factor 2 (Nrf2) activators, CPUY192018, which inhibits glycolysis, boosts antioxidative stress simultaneously and delivers satisfying therapeutic effect in macrophages from COPD patients and cigarette smoke extract induced COPD mice. Furthermore, we clarify that CPUY192018 not only disrupts the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, which liberates Nrf2 to activate the antioxidative pathway but also disrupt the interaction between Keap1 and actin which downregulates glycolysis, boosting the phagocytic function of alveolar macrophage in lung tissue. Taken together, CPUY192018 demonstrates notable effects on counteracting oxidative stress and reprogramming metabolism via Nrf2 activation; hence, being a raising potential therapeutic approach against COPD.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.03.039DOI Listing
June 2021

Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation.

Mol Oncol 2021 Apr 2. Epub 2021 Apr 2.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, School of Medicine, Shenzhen University, China.

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin-specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.
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http://dx.doi.org/10.1002/1878-0261.12958DOI Listing
April 2021

Chemical constituents of Psidium guajava leaves and their antibacterial activity.

Phytochemistry 2021 Jun 31;186:112746. Epub 2021 Mar 31.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:

Seven undescribed compounds, namely (+)-psiflavanone A, (-)-psiflavanone A, (+)-psiflavanone B, (-)-psiflavanone B, (+)-psiketide, (-)-psiketide, and psidinone, were isolated and chirally separated from the 95%-ethanol extract of Psidium guajava leaves. (+)/(-)-Psiflavanone A and (+)/(-)-psiflavanone B are two pairs of rare enantiomeric C-benzoylated flavanones isolated from the title plant for the first time. (+)/(-)-Psiketide are a pair of enantiomeric aromatic polyketides, and psidinone is the first example of a C phenanthrenediquinone with an angle-type 6/6/6 tricyclic skeleton. Their structures were identified by extensive analysis of HRESIMS, UV, IR, NMR, and calculated electronic circular dichroism (ECD) data. Particularly, the structures of (+)-psiflavanone A, (-)-psiflavanone A, (+)-psiflavanone B, and psidinone were further confirmed by X-ray diffraction. Psidinone exhibited antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Mycobacterium Smegmatis mc 155, with minimum inhibitory concentrations (MICs) of 16, 8, and 0.5 μM, respectively. These results not only highlight the chemical diversity and biological activity of P. guajava but are also expected to pave way for its further expansion to other applications in future.
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http://dx.doi.org/10.1016/j.phytochem.2021.112746DOI Listing
June 2021

Elevation of biochar application as regulator on denitrification/NH volatilization in saline soils.

Environ Sci Pollut Res Int 2021 Aug 31;28(31):41712-41725. Epub 2021 Mar 31.

Department of Rural Engineering, Faculty of Agronomy, Federal University of Pelotas, Campus Universitário s/n, CEP, Capão do Leão, Rio Grande do Sul, 96010-900, Brazil.

Denitrification and NH volatilization are the main removal processes of nitrogen in coastal saline soils. In this incubation study, the effects of wheat straw biochar application at rates of 0, 2, 5, 10 and 15% by weight to saline soil with two salt gradients of 0 and 1‰ on denitrification and NH volatilization were investigated. The results showed that the denitrification rates with 2, 5 and 10% biochar amendments decreased by 25.26, 33.07 and 17.50%, respectively, under salt-free conditions, and the denitrification rates with 2 and 5% biochar amendments under 1‰ salt conditions decreased by 17.74 and 17.39%, respectively. However, the NH volatilization rates increased by 8.05-61.73% after biochar application. The path analysis revealed the interactions of overlying water-sediment system environmental factors in biochar-amended saline soils and their roles in denitrification and NH volatilization. Environmental factors in sediment exerted much greater control over denitrification than those in overlying water. In addition, environmental factors exhibited an indirect negative influence on denitrification by negatively influencing the abundance of the nosZ gene. The comprehensive effects of the environmental factors in overlying water on NH volatilization were greater than those in sediment. The NH-N content, pH of overlying water and sediment salinity were the main controlling factors for NH volatilization in saline soils. Biochar application effectively regulated the denitrification rate by changing the environmental factors and denitrifying functional gene abundance, but its application posed a risk of increased NH volatilization mainly by increasing NH-N, EC and pH in overlying water.
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http://dx.doi.org/10.1007/s11356-021-13562-wDOI Listing
August 2021

Irradiation-Induced Activated Microglia Affect Brain Metastatic Colonization of NSCLC Cells via miR-9/ Axis.

Onco Targets Ther 2021 16;14:1911-1922. Epub 2021 Mar 16.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China.

Background And Purpose: Brain metastasis is among the leading causes of death in patients with non-small-cell lung cancer (NSCLC). Through yet unknown mechanisms, prophylactic cranial irradiation (PCI) can significantly decrease the incidence of brain metastases. Given that PCI probably exerts indirect anti-tumoral effects by turning cerebral "soil" unfavorable for the colonization of metastatic tumor "seeds". This study aims to reveal how PCI regulates the brain microenvironment conducing to a reduction in brain metastases.

Materials And Methods: Key markers of M1/M2 microglia types and mesenchymal-to-epithelial transition (MET) were analyzed by qRT-PCR and Western Blot in vitro. The target miR-9 was obtained by miRNA array analysis and confirmed by qRT-PCR in microglia. We used miRTarBase and TargetScan to analyze the target genes of miR-9 and confirmed by luciferase activity assay. Anti-metastatic effects of irradiation on the brain were evaluated by intravital imaging using a brain metastatic A549-F3 cell line in a nude mouse model.

Results: Irradiation induced M1 microglia activation, which inhibited the MET process of A549 cell lines. Furthermore, levels of miR-9 secreted by irradiated M1 microglia significantly increased and played a vital role in the inhibition of the A549 MET process by directly targeting , concurrently decreasing cell capacity for localization in the brain, thus reducing brain metastases.

Conclusion: We demonstrated that miR-9 secreted by irradiated M1-type microglia played an important role in modulating A549 cell lines into mesenchymal phenotype and further decreased their localization capabilities in the brain. Our findings signify the modulating effect of irradiation on metastatic soil and the cross-talk between tumour cells and the metastatic microenvironment; importantly, they provide new opportunities for effective anti-metastasis therapies, especially for brain metastasis patients.
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http://dx.doi.org/10.2147/OTT.S301412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981147PMC
March 2021

Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities.

Molecules 2021 Feb 28;26(5). Epub 2021 Feb 28.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC) 1.63-4.62 μM). Moreover, ()-3-(8-(-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)--((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide () exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, had stronger free-radical scavenging activity. Molecular docking studies revealed that could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate as a leading structure worthy of further investigation.
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http://dx.doi.org/10.3390/molecules26051303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957565PMC
February 2021

Natural Tannins as New Cross-Linking Materials for Soy-Based Adhesives.

Polymers (Basel) 2021 Feb 16;13(4). Epub 2021 Feb 16.

Laboratory of Wood Chemistry and Technology, Department of Forestry and Natural Environment, International Hellenic University, GR-661 00 Drama, Greece.

Human health problems and formaldehyde emission from wood-based composites are some of the major drawbacks of the traditional synthetic adhesives such as urea formaldehyde resins. There have been many attempts to decrease formaldehyde emission and replace urea formaldehyde resins with bio-based adhesives for wood-based composites. Because of some weakness in soy-based adhesive, chemicals have been used as modifiers. Modified soy-based adhesives without any formaldehyde have been successfully used to prepare wood panels. To achieve this, different synthetic cross-linking chemicals such as phenol formaldehyde resins and polyamidoamine-epichlorohydrin were used. However, in reality, what we need are totally green adhesives that use natural materials. In our previous research work, the use of tannins in combination with soy-based adhesives to make wood composites was investigated. Thus, in this research work, the feasibility of using three types of natural tannins (quebracho, mimosa and chestnut tannins) as cross-linking materials for soy adhesive was studied. The chemical bond formation and adhesion behaviors of tannin-modified soy adhesives were also investigated by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-ToF-MS) and thermo-mechanical analysis (TMA). The results showed that at ambient temperature, both ionic and covalent bonds formed between tannin constituents and amino acids; however, at higher temperature, covalent bonds are largely predominate. Based on the results obtained from the thermo-mechanical analysis, the modulus of elasticity (MOE) of soy adhesive is increased by adding tannins to its formulation. In addition, the chemical bond formation was proved by MALDI-ToF-MS.
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http://dx.doi.org/10.3390/polym13040595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920486PMC
February 2021

Resuming Sensitivity of Tamoxifen-Resistant Breast Cancer Cells to Tamoxifen by Tetrandrine.

Integr Cancer Ther 2021 Jan-Dec;20:1534735421996822

Dongfang Hospital affiliated to Beijing University of Traditional Chinese Medicine, Beijing, China.

Background: Tamoxifen is one of the medicines for adjuvant endocrine therapy of hormone-dependent breast cancer. However, development of resistance to tamoxifen occurs inevitably during treatment. This study aimed to determine whether sensitivity of tamoxifen-resistant breast cancer cells (TAM-R) could be reinstated by tetrandrine (Tet).

Methods: All experiments were conducted in TAM-R cells derived from the MCF-7 breast cancer cell line by long-term tamoxifen exposure. Cell growth, apoptosis, and autophagy were end-points that evaluated the effect of Tet (0.9 μg/ml, 1.8 μg/ml, and 3.75 μg/ml) alone or in combination with TAM (1 μM). Cell apoptosis was determined by an ELISA assay and autophagy was determined by fluorescent staining using the Enzo autophagy detection kit. Immunoblotting was used to evaluate markers for apoptosis, autophagy, and related signal pathway molecules.

Results: Growth of TAM-R cells was significantly inhibited by Tet. Combination of Tet with tamoxifen induced a greater inhibition on cell growth than tamoxifen alone, which was predominantly due to enhancement of pro-apoptotic effect of TAM by Tet. Autophagy was significantly inhibited in TAM-R cells treated with Tet plus TAM as shown by increased autophagosomes and the levels of LC3-II and p62. At 0.9 μg/ml, Tet increased the levels of both apoptosis and autophagy markers. Among them increase in p53 levels was more dramatic.

Conclusions: Tet as a monotherapy inhibits TAM-R cells. Tet potentiates the pro-apoptotic effect of TAM via inhibition of autophagy.
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http://dx.doi.org/10.1177/1534735421996822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164553PMC
March 2021

Engineered Microglia Potentiate the Action of Drugs against Glioma Through Extracellular Vesicles and Tunneling Nanotubes.

Adv Healthc Mater 2021 05 28;10(9):e2002200. Epub 2021 Feb 28.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, P. R. China.

Gliomas remain difficult to treat because of their metastatic and recurrent nature and the existence of the blood-brain barrier (BBB), which impedes drug delivery. Microglia, the resident macrophages in the CNS, can be recruited by gliomas and can penetrate the tumor. In this study, microglia (BV2 cells) are used as transport vectors to deliver paclitaxel for the treatment of glioma. To avoid paclitaxel toxicity in microglia, liposomes are first employed to isolate the drug from BV2 cells. Dipalmitoyl phosphatidylserine (DPPS), as an "eat me" signal, is doped into liposomes to amplify their phagocytosis by microglia. This study demonstrates that engineered microglia can cross the BBB, independently migrate toward gliomas, and transfer cargo to glioma cells. Of note, extracellular vesicles and tunneling nanotubes are found to offer unique modes of cargo transportation between microglia and glioma cells. In vivo, the engineered drug-loaded microglia has a high ability to target the brain, penetrate glioma, and suppress tumor progression, supporting the notion that the use of engineered microglia is a potential strategy for the treatment of glioma. These findings present new opportunities for exploration into the use of microglia as transport vectors to deliver therapeutic agents through specific membrane nanotubes and vesicles.
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http://dx.doi.org/10.1002/adhm.202002200DOI Listing
May 2021

Isoquercetin Improves Inflammatory Response in Rats Following Ischemic Stroke.

Front Neurosci 2021 9;15:555543. Epub 2021 Feb 9.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Inflammatory response contributes to brain injury after ischemia and reperfusion (I/R). Our previous literature has shown isoquercetin plays an important role in protecting against cerebral I/R injury. The present study was conducted to further investigate the effect of isoquercetin on inflammation-induced neuronal injury in I/R rats with the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and inhibitor of NF-κB (I-κB)/nuclear factor-kappa B (NF-κB) signaling pathway mediated by Toll-like receptor 4 (TLR4) and C5a receptor 1 (C5aR1). middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and oxygen-glucose deprivation and reperfusion (OGD/R) neuron model were used. MCAO/R induced neurological deficits, cell apoptosis, and release of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in ischemic brain in rats. Simultaneously, the expression of TLR4 and C5aR1 was significantly up-regulated in both MCAO/R rats and OGD/R neurons, accompanied with the inhibition of cAMP/PKA signaling and activation of I-κB/NF-κB signaling in the cortex of MCAO/R rats. Over-expression of C5aR1 in neurons induced decrease of cell viability, exerting similar effects with OGD/R injury. Isoquercetin acted as a neuroprotective agent against I/R brain injury to suppress inflammatory response and improve cell recovery by inhibiting TLR4 and C5aR1 expression, promoting cAMP/PKA activation, and inhibiting I-κB/NF-κB activation and Caspase 3 expression. TLR4 and C5aR1 contributed to inflammation and apoptosis via activating cAMP/PKA/I-κB/NF-κB signaling during cerebral I/R, suggesting that this signaling pathway may be a potent therapeutic target in ischemic stroke. Isoquercetin was identified as a neuroprotective agent, which maybe a promising therapeutic agent used for the treatment of ischemic stroke and related diseases.
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http://dx.doi.org/10.3389/fnins.2021.555543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900503PMC
February 2021

Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer.

Mol Cancer 2021 02 19;20(1):36. Epub 2021 Feb 19.

Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, 325027, China.

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.
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http://dx.doi.org/10.1186/s12943-021-01330-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893735PMC
February 2021

Hilar cholangiocarcinoma: Value of high-resolution enhanced magnetic resonance imaging for preoperative evaluation.

J Cancer Res Ther 2020 ;16(7):1634-1640

Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University; Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Objectives: The objective is to assess the accuracy of high-resolution (HR) enhanced magnetic resonance imaging (MRI) images in the preoperative evaluation of biliary and vascular invasion in hilar cholangiocarcinomas.

Methods: This retrospective study included 36 patients with hilar cholangiocarcinoma who underwent enhanced HR-MRI with an effective section thickness of 1.2 mm at 3.0 T before surgery. Combined HR-MRI and magnetic resonance cholangiopancreatography (MRCP) images were compared with MRCP in evaluating the extent of biliary infiltration according to the Bismuth-Corlette classification. To determine the suitable criterion for HR-MRI in predicting vessel invasion, Labeling 180 and 90 of circumferential contact of the tumor with the vessel were used to predict the invasion. The correlation between imaging findings and surgical and histopathological records was statistically analyzed.

Results: The accuracy in detecting biliary neoplastic invasion was higher for combined HR-MRI images (97.2%) than MRCP images (86.1%). HR-MRI images increased the accuracy in delineation of the tumor biliary extent (P < 0.05). The accuracy of Labeling 90 (98.6% in portal venous system and 98.0% in hepatic arterial system) was higher than that of Labeling 180 (96.5% in portal venous system and 94.6% in hepatic arterial system). However, there was no significant statistic difference between them (P > 0.05). Interobserver agreement was high with respect to biliary tract, portal venous, and hepatic arterial system involvement.

Conclusions: Enhanced HR-MRI images showed excellent capability for assessing tumor extent and vascular invasion in hilar cholangiocarcinomas. More than 90° of circumferential contact of the tumor with the vessel on HR-MRI may be an appropriate criterion for predicting invasion.
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http://dx.doi.org/10.4103/jcrt.JCRT_140_20DOI Listing
January 2020

Children as messengers of health knowledge? Impact of health promotion and water infrastructure in schools on facial cleanliness and trachoma in the community.

PLoS Negl Trop Dis 2021 02 1;15(2):e0009119. Epub 2021 Feb 1.

Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States of America.

Background: Health promotion is essential to the SAFE strategy for trachoma elimination. Schools are a valuable venue for health promotion. However, there is little literature about the impact of health education and water infrastructure in schools on facial cleanliness and trachoma in the community. Our study aimed to describe the current state of school health promotion in Kongwa, Tanzania, and to examine the transferability of health messages from schools to the community at large.

Methodology/findings: A cross-sectional survey was carried out in all 92 villages in Kongwa district, which included 85 primary schools. Data were collected on health messages and water infrastructure in the schools. A random sample of 3084 children aged 0-5 were examined for facial cleanliness in all villages. In 50 villages, a random sample of 50 children aged 1-9 per village were examined for follicular trachoma (TF). Thirty-seven (44.6%) schools had educational materials on face-washing. Fifty (60.2%) schools had a washing station. The presence of a health teacher was correlated with having posters on face washing in classrooms. The presence of face-washing materials was correlated with the availability of washing stations. Neither teachers mentioning face-washing in health curricula nor educational materials in classrooms were associated with clean faces or trachoma in the community. Having a washing station in the school was associated with lower community rates of trachoma.

Conclusions: Primary school health messages and materials on trachoma were not associated with clean faces or lower rates of trachoma in the community. The target audience for primary school health promotion is likely the students themselves, without immediate rippling effects in the community. A long-term perspective should be considered during the implementation of health promotion in schools. The goal of school health promotion should be training the next generation of parents and community health leaders in combatting trachoma.
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http://dx.doi.org/10.1371/journal.pntd.0009119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877774PMC
February 2021

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications.

Sci Rep 2021 01 28;11(1):2519. Epub 2021 Jan 28.

Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA.

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb's ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.
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http://dx.doi.org/10.1038/s41598-021-81620-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844014PMC
January 2021

Non-Furanic Humins-Based Non-Isocyanate Polyurethane (NIPU) Thermoset Wood Adhesives.

Polymers (Basel) 2021 Jan 25;13(3). Epub 2021 Jan 25.

Department of Chemistry, University of the Cote d'Azur, 06103 Nice, France.

Predominantly non-furanic commercial humins were used to prepare humin-based non-isocyanate polyurethane (NIPU) resins for wood panel adhesives. Pure humin-based NIPU resins and tannin-humin NIPU resins were prepared, the latter to upgrade the humins' performance. Species in the raw humins and species formed in the NIPU resins were identified by Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI ToF) spectrometry and Fourier Transform Infrared (FTIR). Humins, fulvic acid and derivatives, humic acid and its fragments, some lignans present and furanic oligomers present formed NIPU linkages. Thermomechanical analysis (TMA) showed that as with other biomaterials-based NIPU resins, all these resins also showed two temperature peaks of curing, the first around 130 °C and the second around 220 °C. A decrease in the Modulus of Elasticity (MOE) between the two indicated that the first curing period corresponded to linear growth of the oligomers forming a physical entanglement network. This then disentangled, and the second corresponded to the formation of a chemical cross-linked network. This second peak was more evident for the tannin-humin NIPU resins. All the laboratory particleboard made and tested either bonded with pure humins or with tannin-humin NIPU adhesives satisfied well the internal bond strength requirements of the relevant standard for interior grade panels. The tannin-humin adhesives performed clearly better than the pure humins one.
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http://dx.doi.org/10.3390/polym13030372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865859PMC
January 2021
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