Publications by authors named "Rui Zhang"

4,439 Publications

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Urinary exosomal circular RNAs of sex chromosome origin are associated with gender-related risk differences of clinicopathological features in patients with IgA nephropathy.

J Nephrol 2021 Jul 22. Epub 2021 Jul 22.

Department of Nephrology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, Jilin, China.

Background: There are arguments for individualized treatments and the necessity of non-invasive biomarkers for patients with IgA nephropathy (IgAN) according to gender, but the rationale remains unclear. We aimed to investigate the relationship between urine exosomal circular RNA (circRNA) levels, related genes, clinical features, and renal pathological features in IgA nephropathy patients of different genders.

Methods: Clinicopathological data from patients of different genders from a multicenter cohort were retrospectively analyzed. We used the Oxford classification to examine the severity of pathological damage in these patients. We compared clinical features and renal pathologies between IgAN patients of different genders. Using findings of urine exosomal circRNAs from male IgAN patients, we analyzed the relationship between this factor, the regulated genes located on the sex chromosomes, and renal pathologies.

Results: A total of 502 IgAN patients were included. The proportion of male patients with crescent formation was higher than that of females (p = 0.019). Multivariate logistic regression analysis showed that proteinuria was an independent marker for crescent formation in male and female patients with IgAN, while smoking and higher low-density lipoprotein cholesterol (LDL-C) levels were independent risk factors for crescent formation in males alone. Urine exosomal circRNA chrY:15478147-15481229- located on the Y chromosome in male patients was negatively correlated with the expressions of UTY in specific regions of the Y chromosome.

Conclusion: Compared with female patients, males with IgAN had more severe renal dysfunction and a higher probability of glomerular crescent formation. Urine exosomal circRNA chrY:15478147-15481229- might participate in the pathogenesis of IgAN in male patients by altering UTY expressions.
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http://dx.doi.org/10.1007/s40620-021-01118-7DOI Listing
July 2021

SD-36 promotes growth inhibition and induces apoptosis via suppression of Mcl-1 in glioma.

J Cell Mol Med 2021 Jul 21. Epub 2021 Jul 21.

Department of Neurosurgery, Xingtai People's Hospital, Hebei Province, China.

Glioma is one of the most commonly observed tumours, representing approximately 75% of brain tumours in the adult population. Generally, glioma therapy includes surgical resection followed by radiotherapy and chemotherapy. The transcription factor STAT3 (signal transducer and activator of transcription 3) is a promising target for the treatment of cancer and several other diseases. At nanomolar concentrations, SD-36 induces rapid cellular degradation of STAT3 but cannot degrade other STAT proteins. The current study demonstrates the therapeutic efficacies of the STAT3 degraders SD-36 against glioma, as well as understanding the elucidating mechanisms and identifying molecular markers that determine cell sensitivity to STAT3 degraders. Glioma cell lines possessed similar response patterns to SD-36 but different responses to the STAT3 inhibitor Stattic. SD-36 potently induced apoptosis in glioma cells along with a reduction in Mcl-1 levels, which are critical for mediating the induction of apoptosis and enhancing TMZ-induced apoptosis. Accordingly, SD-36 sensitizes the antitumour effect of TMZ in patient-derived xenograft. In addition, the downregulation of Mcl-1 expression-mediated antitumour effect of SD-36 was analysed in cell-derived xenograft. These observations need to be validated clinically to confirm the efficacy of STAT3 degraders in glioma.
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http://dx.doi.org/10.1111/jcmm.16754DOI Listing
July 2021

Lifetime ambient ultraviolet radiation exposure and risk of basal cell carcinoma by anatomic site in a nationwide US cohort, 1983-2005.

Cancer Epidemiol Biomarkers Prev 2021 Jul 21. Epub 2021 Jul 21.

Radiation Epidemiology Branch, National Cancer Institute.

Background: Cutaneous basal cell carcinoma (BCC) has long been associated with ultraviolet radiation (UVR) exposure, but data are limited on risks by anatomic site.

Methods: We followed 63,912 cancer-free White US radiologic technologists from cohort entry (1983-1989/1994-1998) to exit (date first BCC via 2003-2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models.

Results: For incident first primary BCC in 2124 subjects (mean follow-up 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR=1.27/MJ cm-2 (95% CI: 0.86, 1.68; p-trend<0.001) did not vary by anatomic site (p=0.153). However, excess absolute risks (EAR) of BCC per unit cumulative ambient UVR were large for the head/neck=5.46/MJ cm-2/104 person-year (95% CI: 2.92, 7.36; p-trend<0.001), smaller for the trunk (2.56; 95% CI: 1.26, 3.33; p-trend=0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (p<0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5-15 years before time of follow-up.

Conclusions: BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk.

Impact: These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1815DOI Listing
July 2021

Association between ARDS Etiology and Risk of Noninvasive Ventilation Failure.

Ann Am Thorac Soc 2021 Jul 21. Epub 2021 Jul 21.

The First Affiliated Hospital of Chongqing Medical University, 117972, Department of Respiratory and Critical Care Medicine, Chongqing, Sichuan, China;

Rationale: The etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV).

Objectives: To explore the association between ARDS etiology and risk of noninvasive ventilation failure.

Methods: A multicenter prospective observational study was performed in 17 ICUs in China from September 2017 to December 2019. Patients with ARDS who used NIV as a first-line therapy were enrolled. The etiology of ARDS was recorded at study entry.

Results: A total of 306 patients were enrolled. Of the patients, 146 were classified as having pulmonary ARDS (ARDSp) and 160 were classified as having extrapulmonary ARDS (ARDSexp). From initiation to 24 h of NIV, the respiratory rate, heart rate, PaO2/FiO2, and PaCO2 improved slower in patients with ARDSp than those with ARDSexp. Patients with ARDSp experienced more NIV failure (55% vs. 28%; p < 0.01) and higher 28-day mortality (47% vs. 14%; p < 0.01). The adjusted odds ratio of NIV failure and 28-day mortality were 5.47 (95%CI: 3.04-9.86) and 10.13 (95%CI: 5.01-20.46), respectively. In addition, we combined the presence of ARDSp, presence of septic shock, age, non-pulmonary SOFA score, respiratory rate at 1-2 h of NIV, and PaO2/FiO2 at 1-2 h of NIV to develop a risk score of NIV failure. With the increase of the risk score, the rate of NIV failure increased. Using 5.5 as cutoff value to predict NIV failure, the sensitivity and specificity was good both in training and validation cohorts.

Conclusions: Among patients with ARDS who used NIV as a first-line therapy, ARDSp was associated with slower improvement, more NIV failure, and higher 28-day mortality than ARDSexp. The risk score combined presence of ARDSp, presence of septic shock, age, non-pulmonary SOFA score, respiratory rate at 1-2 h of NIV, and PaO2/FiO2 at 1-2 h of NIV has high accuracy to predict NIV failure among ARDS population.
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http://dx.doi.org/10.1513/AnnalsATS.202102-161OCDOI Listing
July 2021

Switchable and Scalable Heteroarylation of Primary Amines with 2-Chlorobenzothiazoles under Transition-Metal-Free and Solvent-Free Conditions.

J Org Chem 2021 Jul 21. Epub 2021 Jul 21.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, P. R. China.

2-Aminobenzothiazoles comprise a valuable structural motif, which prevails in versatile natural products and biologically active compounds. Herein, a switchable and scalable C-N coupling protocol was developed for the synthesis of these compounds from 2-chlorobenzothiazoles and primary amines. Gratifyingly, this protocol was achieved under transition-metal-free and solvent-free conditions. Moreover, introducing an appropriate amount of NaH completely switched the selectivity from mono- toward di-heteroarylation, and further investigations provided a rationale for this new finding. Furthermore, gram-scale synthesis of representative products and was realized by applying operationally simple and glovebox-free procedures, which revealed the practical usefulness of this work. Finally, evaluation of the quantitative green metrics provided evidence that our protocol was superior over the literature ones in terms of green chemistry and sustainability.
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http://dx.doi.org/10.1021/acs.joc.1c01019DOI Listing
July 2021

MiR-342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death.

EMBO Rep 2021 Jul 20:e52252. Epub 2021 Jul 20.

School of Life Sciences, Chongqing University, Chongqing, China.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb-susceptible mice and TB patients have relatively low miR-342-3p expression, while mice with miR-342-3p overexpression are more resistant to Mtb. We demonstrate that the miR-342-3p/SOCS6 axis regulates anti-Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR-342-3p/SOCS6 axis participates in the switching between Mtb-induced apoptosis and necrosis through A20-mediated K48-linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA-mRNA network and pave the way for host-directed therapies targeting these pathways.
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http://dx.doi.org/10.15252/embr.202052252DOI Listing
July 2021

TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer.

Nat Commun 2021 07 20;12(1):4413. Epub 2021 Jul 20.

Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College, Fudan University, Shanghai, China.

Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.
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http://dx.doi.org/10.1038/s41467-021-24703-7DOI Listing
July 2021

Lattice Defect Engineering Enables Performance-Enhanced MoS Photodetection through a Paraelectric BaTiO Dielectric.

ACS Nano 2021 Jul 20. Epub 2021 Jul 20.

Key Laboratory of LCR Materials and Devices of Yunnan Province National Centre for International Research on Photoelectric and Energy Materials School of Materials and Energy Yunnan University Kunming 650500, P.R. China.

Carrier mobility and density are intrinsically important in nanophoto/electronic devices. High-dielectric-constant coupled polarization-field gate ferroelectrics are frequently studied and partially capable in achieving large-scale tuning of photoresponse, but their light absorption and carrier density seem generally ineffective. This raises questions about whether a similarly high-dielectric-constant paraelectric gate dielectric could enable tuning and how the principles involved could be established. In this study, by deliberately introducing lattice defects in high-dielectric-constant paraelectric, cubic BaTiO (c-BTO) was explored to fabricate MoS photodetectors with ultrahigh detection ability and outstanding field-effect traits. An organic-metal-based spin-coating cum annealing method was used for the c-BTO synthesis, with an optimized thickness (300 nm), by introducing lattice defects properly but maintaining a large dielectric constant (55 at 1k Hz) and low dielectric loss (0.06 at 1k Hz), which renders the enhanced visible-light region absorption. As a result of the synergistically enhanced mobility and photoabsorption, the MoS/BTO FET exhibits promising merits, for example, on/off ratio, subthreshold swing, and mobilities for high-performance photodetectors with excellent responsivity (600 AW) and detectivity (1.25 × 10 Jones). Thus, this work facilitates the establishment of a lattice defect induced sub-bandgap absorption landmap for synergistically enhanced photoresponse for high-performance photodetector exploration.
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http://dx.doi.org/10.1021/acsnano.1c03402DOI Listing
July 2021

Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles.

J Heart Lung Transplant 2021 Jun 24. Epub 2021 Jun 24.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Extracellular vesicles (EVs) from heart stromal/progenitor cells modulate innate immunity, with salutary effects in a variety of cardiac disease models. Little is known, however, about the effects of these EVs on adaptive immunity.

Methods: Ex vivo differentiation of naïve CD4 T cells was conducted to assess the effect of EVs on cytokine production and proliferation of Th1, Th2, Th17, and regulatory T (T) cells. These effects were further tested in vivo using the experimental autoimmune myocarditis (EAM) model.

Results: Using differentiated CD4 T cells, we show that EVs secreted by human-derived heart stromal/progenitor cells selectively influence the phenotype, activity, and proliferation of regulatory T (T) cells. Exposure of T cells to EVs results in faster proliferation, augmented production of IL-10, and polarization toward an intermediate FOXP3RORγt phenotype. In experimental autoimmune myocarditis, EVs attenuate cardiac inflammation and functional decline, in association with increased numbers of splenic IL10-T cells.

Conclusions: T cell modulation by EVs represents a novel therapeutic approach to inflammation, harnessing endogenous immunosuppressive mechanisms that may be applied in solid organ transplantation, graft-versus-host disease, and autoimmune disorders.
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http://dx.doi.org/10.1016/j.healun.2021.06.005DOI Listing
June 2021

Data Comparison and Software Design for Easy Selection and Application of CRISPR-based Genome Editing Systems in Plants.

Genomics Proteomics Bioinformatics 2021 Jul 16. Epub 2021 Jul 16.

Beijing Key Laboratory of Grape Science and Enology, and CAS Key Laboratory of Plant Resources, Institute of Botany, the Innovative Academy of Seed Design, Chinese Academy of Science, Beijing 100093, China; Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan 430074, China. Electronic address:

CRISPR-based genome editing systems have been successfully and effectively used in many organisms. However, only a few studies have reported the comparison between CRISPR/Cas9 and CRISPR/Cpf1 systems in the whole-genome applications. Although many web-based toolkits are available, there is still a shortage of comprehensive, user-friendly, and plant-specific CRISPR databases and desktop software. In this study, we identified and analyzed the similarities and differences between CRISPR/Cas9 and CRISPR/Cpf1 systems by considering the abundance of proto-spacer adjacent motif (PAM) sites, effects of GC content, optimal proto-spacer length, potential universality within the plant kingdom, PAM-rich region (PARR) inhibiting ratio, and effects of G-quadruplex (G-Q) structures. Using this information, we built a comprehensive CRISPR database (including 138 plant genome data sources, www.grapeworld.cn/pc/index.html), which provides search tools for the identification of CRISPR editing sites in both CRISPR/Cas9 and CRISPR/Cpf1 systems. We also developed a desktop software on the basis of Perl/TK tool, which facilitates and improves the detection and analysis of CRISPR editing sites at the whole-genome level on Linux and/or Windows platform. Therefore, this study provides helpful data and software for easy selection and application of CRISPR-based genome editing systems in plants.
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http://dx.doi.org/10.1016/j.gpb.2019.05.008DOI Listing
July 2021

Lin28A promotes the proliferation and stemness of lung cancer cells via the activation of mitogen-activated protein kinase pathway dependent on microRNA let-7c.

Ann Transl Med 2021 Jun;9(12):982

Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.

Background: Among patients with lung cancer, metastatic and relapsed cases account for the largest proportion of disease-associated deaths. Tumor metastasis and relapse are believed to originate from cancer stem cells (CSCs), which have the capacity to be highly proliferative and invasive. In our previous studies, we established a conditional basement membrane extract-based (BME-based) 3-dimensional (3D) culture system to mimic the tumor growth environment and further amplified lung cancer stem cells (LCSCs) in our system. However, the molecular mechanisms of LCSC amplification and development in our 3D culture system have not been fully uncovered.

Method: We established the conditional 3D culture system to amplify LCSCs in other lung cancer cell lines, followed by examining the expression of Lin28A and let-7 microRNAs in them. We also explored the expression of Lin28A and let-7 microRNAs in LCSCs from clinical lung cancer tissue samples and even analyzed the correlation of Lin28A/let-7c and patients' survival outcomes. We further constructed A549 cells either knockdown of Lin28A or overexpression of let-7c, followed by investigating stemness marker gene expression, and stemness phenotypes including mammosphere culture, cell migration and invasion , as well as tumorigenicity .

Results: Here, we observed that Lin28A/let-7c was dysregulated in LCSCs in both the 3D culture system and lung cancer tissues. Further, the abnormal expression of Lin28A/let-7c was correlated with poor survival outcomes. Via the construction of A549 cells with let-7c over-expression, we found that let-7c inhibited the maintenance of LCSC properties, while the results of Lin28A knockdown showed that Lin28A played a critical role in the enrichment and proliferation of LCSCs via mitogen-activated protein kinase (MAPK) signaling pathway. Importantly, we found that LCSCs with knockdown of Lin28A or over-expression of let-7c exhibited inhibited carcinogenesis and disrupted expansion .

Conclusions: Our study uncovered the functions and mechanisms of the Lin28A/let-7c/MAPK signaling pathway in promoting the proliferation and cancer stemness of LCSCs, which might be a potential therapeutic target for reducing and even eliminating LCSCs in the future.
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http://dx.doi.org/10.21037/atm-21-2124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267304PMC
June 2021

The Association Between Quantitative Flow Ratio and Intravascular Imaging-defined Vulnerable Plaque Characteristics in Patients With Stable Angina and Non-ST-segment Elevation Acute Coronary Syndrome.

Front Cardiovasc Med 2021 30;8:690262. Epub 2021 Jun 30.

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome. Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups. This analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) ( = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area ( = 0.017, 0.040, and <0.001, respectively). Thrombus was more prevalent in QFR-T1 (39%) than in QFR-T2 (3%), and QFR-T3 (12%) ( = 0.001 and 0.020, respectively). In the multivariable analysis, QFR ≤ 0.80 remained as a significant determinant of OCT-TCFA regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted OR: 4.387, 95% CI 1.297-14.839, = 0.017). The diagnostic accuracy of QFR was moderate in identifying lesions with OCT-TCFA (area under the curve: 0.72, 95% CI 0.58-0.86, = 0.003). In the IVUS cohort, significant differences were found between two groups in minimal lumen area and plaque burden but not in the distribution of virtual histology (VH)-TCFA ( = 0.025, 0.036, and 1.000, respectively). Lower QFR was related to OCT-defined plaque vulnerability in angiographically mild-to-intermediate lesions. The QFR might be a useful tool for ruling out high-risk plaques without using any pressure wire or vasodilator.
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http://dx.doi.org/10.3389/fcvm.2021.690262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278311PMC
June 2021

Oxygen-Based Nanocarriers to Modulate Tumor Hypoxia for Ameliorated Anti-Tumor Therapy: Fabrications, Properties, and Future Directions.

Front Mol Biosci 2021 1;8:683519. Epub 2021 Jul 1.

Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

Over the past five years, oxygen-based nanocarriers (NCs) to boost anti-tumor therapy attracted tremendous attention from basic research and clinical practice. Indeed, tumor hypoxia, caused by elevated proliferative activity and dysfunctional vasculature, is directly responsible for the less effectiveness or ineffective of many conventional therapeutic modalities. Undeniably, oxygen-generating NCs and oxygen-carrying NCs can increase oxygen concentration in the hypoxic area of tumors and have also been shown to have the ability to decrease the expression of drug efflux pumps (e.g., P-gp); to increase uptake by tumor cells; to facilitate the generation of cytotoxic reactive oxide species (ROS); and to evoke systematic anti-tumor immune responses. However, there are still many challenges and limitations that need to be further improved. In this review, we first discussed the mechanisms of tumor hypoxia and how it severely restricts the therapeutic efficacy of clinical treatments. Then an up-to-date account of recent progress in the fabrications of oxygen-generating NCs and oxygen-carrying NCs are systematically introduced. The improved physicochemical and surface properties of hypoxia alleviating NCs for increasing the targeting ability to hypoxic cells are also elaborated with special attention to the latest nano-technologies. Finally, the future directions of these NCs, especially towards clinical translation, are proposed. Therefore, we expect to provide some valued enlightenments and proposals in engineering more effective oxygen-based NCs in this promising field in this comprehensive overview.
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http://dx.doi.org/10.3389/fmolb.2021.683519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281198PMC
July 2021

Survival in severe pulmonary hypertension due to chronic lung disease: influence of in-hospital platelet distribution width.

Pulm Circ 2021 Jul-Sep;11(3):20458940211026484. Epub 2021 Jun 30.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Platelet distribution width has been recognized as risk predictors of idiopathic pulmonary arterial hypertension. This study aims to investigate whether in-hospital platelet distribution width would be useful to predict all-cause death in patients with severe pulmonary hypertension due to chronic lung diseases (CLD-PH). Early in-hospital platelet distribution width was measured in 67 severe CLD-PH patients who were confirmed by right heart catheterization and followed up. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the association between the platelet distribution width level and all-cause death. During median of 2.4 (2.5, 3.7) years of follow-up, 44 patients died. A significant association was noted between in-hospital platelet distribution width level and the adjusted risk of all-cause mortality (hazard ratio: 1.245; 95% confidence interval: 1.117-1.386,  < 0.001). Compared with those with platelet distribution width <16.1%, the hazard ratio for all-cause death increased by 5.278 (95% confidence interval: 2.711-10.276,  < 0.0001) among patients with platelet distribution width ≥16.1%. Higher levels of platelet distribution width were also associated with increased risk of all-cause death. In-hospital platelet distribution width was independently associated with all-cause death in patients with severe CLD-PH. This potentially could be used to estimate the severity of severe CLD-PH.
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http://dx.doi.org/10.1177/20458940211026484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258768PMC
June 2021

Drug-drug cocrystals: Opportunities and challenges.

Asian J Pharm Sci 2021 May 9;16(3):307-317. Epub 2020 Jul 9.

Department of Phamacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Recently, drug-drug cocrystal attracts more and more attention. It offers a low risk, low-cost but high reward route to new and better medicines and could improve the physiochemical and biopharmaceutical properties of a medicine by addition of a suitable therapeutically effective component without any chemical modification. Having so many advantages, to date, the reported drug-drug cocrystals are rare. Here we review the drug-drug cocrystals that reported in last decade and shed light on the opportunities and challenges for the development of drug-drug cocrystals.
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http://dx.doi.org/10.1016/j.ajps.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261079PMC
May 2021

RUVBL1/2 Complex Regulates Pro-Inflammatory Responses in Macrophages Regulating Histone H3K4 Trimethylation.

Front Immunol 2021 4;12:679184. Epub 2021 Jun 4.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.

Macrophages play an important role in the host defense mechanism. In response to infection, macrophages activate a genetic program of pro-inflammatory response to kill any invading pathogen, and initiate an adaptive immune response. We have identified RUVBL2 - an ATP-binding protein belonging to the AAA+ (ATPase associated with diverse cellular activities) superfamily of ATPases - as a novel regulator in pro-inflammatory response of macrophages. Gene knockdown of , or pharmacological inhibition of RUVBL1/2 activity, compromises type-2 nitric oxide synthase () gene expression, nitric oxide production and anti-bacterial activity of mouse macrophages in response to lipopolysaccharides (LPS). RUVBL1/2 inhibitor similarly inhibits pro-inflammatory response in human monocytes, suggesting functional conservation of RUVBL1/2 in humans. Transcriptome analysis further revealed that major LPS-induced pro-inflammatory pathways in macrophages are regulated in a RUVBL1/2-dependent manner. Furthermore, RUVBL1/2 inhibition significantly reduced the level of histone H3K4me3 at the promoter region of and , two prototypical pro-inflammatory genes, and diminished the recruitment of NF-kappaB to the corresponding enhancers. Our study reveals RUVBL1/2 as an integral component of macrophage pro-inflammatory responses through epigenetic regulations, and the therapeutic potentials of RUVBL1/2 inhibitors in the treatment of diseases caused by aberrant activation of pro-inflammatory pathways.
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http://dx.doi.org/10.3389/fimmu.2021.679184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282052PMC
June 2021

Experiences and needs of home caregivers for enteral nutrition: A systematic review of qualitative research.

Nurs Open 2021 Jul 17. Epub 2021 Jul 17.

The First Hospital of Jilin University, Changchun, Jilin Province, China.

Aims: To systematically identify, evaluate and synthesize the qualitative evidence on enteral nutrition of home caregivers.

Design: A qualitative evidence synthesis using the Sandelowski and Barroso methodology.

Data Sources: We reviewed articles from eight databases: CINAHL, Embase, PubMed, Web of Science, Cochrane, CNKI, Wanfang Data and CSTJ. Qualitative, peer-reviewed, original studies published in English or Chinese before April 2020 on home caregivers' experience and needs for enteral nutrition were included. The studies were selected by screening titles, abstracts and full texts, and the quality of each study was assessed by two researchers independently.

Review Methods: Two researchers independently used qualitative assessment and review tools for quality assessment and thematic synthesis for data analysis.

Results: This review included 10 articles. The themes identified included balance the enteral nutrition, the experiences and feelings in practice and the recommendations to meet challenge.

Conclusion: Home caregivers reported that they played an important role and faced greater pressure. Future studies should establish a systematic and standardized follow-up schedule to improve home caregivers' physical and mental health.

Impact: The findings established that home caregivers experienced not only changes in their roles and concerns but also spiritual changes. Home caregivers develop different coping strategies to adapt to enteral nutrition without standardized training and support. Although home caregivers make much account of enteral nutrition and feeding issues, they lack of information and support services. Understanding existing problems from a caregiver's perspective can allow interventions to be more clearly developed and well-established training standards established in the future.
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http://dx.doi.org/10.1002/nop2.990DOI Listing
July 2021

Pseudorabies Virus DNA Polymerase Processivity Factor UL42 Inhibits Type I IFN Response by Preventing ISGF3-ISRE Interaction.

J Immunol 2021 Jul 16. Epub 2021 Jul 16.

College of Veterinary Medicine, China Agricultural University, Beijing, China; and

Alphaherpesviruses are large dsDNA viruses with an ability to establish persistent infection in hosts, which rely partly on their ability to evade host innate immune responses, notably the type I IFN response. However, the relevant molecular mechanisms are not well understood. In this study, we report the UL42 proteins of alphaherpesvirus pseudorabies virus (PRV) and HSV type 1 (HSV1) as a potent antagonist of the IFN-I-induced JAK-STAT signaling pathway. We found that ectopic expression of UL42 in porcine macrophage CRL and human HeLa cells significantly suppresses IFN-α-mediated activation of the IFN-stimulated response element (ISRE), leading to a decreased transcription and expression of IFN-stimulated genes (ISGs). Mechanistically, UL42 directly interacts with ISRE and interferes with ISG factor 3 (ISGF3) from binding to ISRE for efficient gene transcription, and four conserved DNA-binding sites of UL42 are required for this interaction. The substitution of these DNA-binding sites with alanines results in reduced ISRE-binding ability of UL42 and impairs for PRV to evade the IFN response. Knockdown of UL42 in PRV remarkably attenuates the antagonism of virus to IFN in porcine kidney PK15 cells. Our results indicate that the UL42 protein of alphaherpesviruses possesses the ability to suppress IFN-I signaling by preventing the association of ISGF3 and ISRE, thereby contributing to immune evasion. This finding reveals UL42 as a potential antiviral target.
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http://dx.doi.org/10.4049/jimmunol.2001306DOI Listing
July 2021

Hypoxic preconditioning reduces NLRP3 inflammasome expression and protects against cerebral ischemia/reperfusion injury.

Neural Regen Res 2022 Feb;17(2):395-400

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning; 1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis; upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue; and increased expression levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China (approval No. DWLL2019001) in November 2019.
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http://dx.doi.org/10.4103/1673-5374.314317DOI Listing
February 2022

Rhamnazin Ameliorates Traumatic Brain Injury in Mice via Reduction in Apoptosis, Oxidative Stress, and Inflammation.

Neuroimmunomodulation 2021 Jul 15:1-8. Epub 2021 Jul 15.

Department of Neurosurgery, Hulunbeier People's Hospital, Hulunbeier, China.

Background: Traumatic brain injury (TBI) is posing serious health challenges for people across the globe due to high morbidity and mortality. However, none of the agents prevents or limits the damage caused by TBI because of its multifactorial etiology. Thus, the discovery of novel agents which can act via several pathways could serve the purpose and afford favorable consequence against TBI. Therefore, in the present article, we intended to investigate the protective effect of rhamnazin (RMZ), a dimethoxyflavone against experimentally induced TBI in mice.

Methods: The effect of RMZ was investigated on cerebral edema and grip test score after induction of experimental brain injury in rats. The effect of RMZ was also investigated on neuronal degeneration in brain tissues of the experimental mice via Nissl staining and flow cytometry analysis. The expression of Bax and Bcl-2 was also quantified using Western blot analysis. The level of inflammatory cytokines (TNF-α and IL-1β) and oxidative stress markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) was also determined using enzyme-linked immunosorbent assay.

Results: RMZ showed a significant reduction in edema and improved grip strength. It also prevented neuronal degeneration via inhibition of neuronal apoptosis as shown by flow cytometry analysis. RMZ showed an antiapoptotic effect via reduction of Bax and increased the expression of Bcl-2 in Western blot analysis. It also showed to inhibit oxidative stress and inflammation compared to the TBI group.

Conclusion: Collectively, our study is first to demonstrate the protective effect of RMZ against experimentally induced TBI in rats.
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http://dx.doi.org/10.1159/000516927DOI Listing
July 2021

Transcriptome analysis reveals potential mechanisms of the effects of dietary Enteromorpha polysaccharides on bursa of Fabricius in broilers.

Vet Med Sci 2021 Jul 15. Epub 2021 Jul 15.

Department of Animal Science, College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, Guangdong Province, P. R. China.

The present study was conducted to evaluate the effects of dietary supplementation of Enteromorpha polysaccharides (EP) on relative organ weight of broilers, and RNA-seq technique was used to reveal the potential molecular mechanisms of the positive effects of EP on relative organ weight. A total of 396 1-day-old male chicks (Arbor Acres) were randomly assigned to six dietary treatments containing EP at 0 (EP0), 1000 (EP1000), 2500 (EP2500), 4000 (EP4000), 5500 (EP5500), and 7000 (EP7000) mg/kg levels for a 35-day feeding trial. At the end of feeding trail, six birds (one bird from each replicate cage) were randomly selected from each treatment and then slaughtered for relative organ weight analysis. The results showed that the relative weight of bursa of Fabricius were increased in the EP1000 group (p < 0.05), and then three bursa of Fabricius samples from each group (EP0 and EP1000) were randomly selected for RNA-seq analysis. The results of RNA-seq analysis showed that there were 20 differentially expressed genes (DEGs) between EP0 and EP1000 groups, among the DEGs, 6 genes were upregulated and 14 genes were downregulated by EP1000 supplementation (p-adjust < 0.05). Gene ontology (GO) enrichment analysis suggested that the DEGs were mainly enriched in negative regulation of toll-like receptor 9 signaling pathway (p-corrected < 0.05). Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the DEGs were mainly enriched in phagosome, mitophagy-animal, Salmonella infection, autophagy-animal signaling pathways (p-corrected = 0.081). Taken together, dietary EP supplementation at 1000 mg/kg level promoted the relative weight of bursa of Fabricius may be involved in improving the immune function of broilers. These findings provided a reference for further exploring the specific molecular mechanism of EP that affecting the organ development in broilers.
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http://dx.doi.org/10.1002/vms3.573DOI Listing
July 2021

Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward.

J Clin Invest 2021 Jul 15. Epub 2021 Jul 15.

National Institute on Drug Abuse, NIH, Bethesda, United States of America.

Background: Certain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude) and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.

Methods: We examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, age: 42.40±12.22) and its relationship to drug reward. Rest-activity rhythms were assessed by one-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride Positron Emission Tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.

Results: We found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or 'social jet lag', whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.

Conclusion: These findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.

Trial Registration: ClinicalTrials.gov: NCT03190954FUNDING. This work was accomplished with support from the National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).
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http://dx.doi.org/10.1172/JCI149722DOI Listing
July 2021

Salvage of severe knee osteoarthritis: efficacy of tibial condylar valgus osteotomy versus open wedge high tibial osteotomy.

J Orthop Surg Res 2021 Jul 14;16(1):451. Epub 2021 Jul 14.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.

Introduction: To compare the clinical outcomes and the radiographic features between tibial condylar valgus osteotomy (TCVO) and open wedge high tibial osteotomy (OWHTO). New insight into the indication criteria for TCVO was also clarified for achieving satisfactory results.

Materials And Methods: Sixty-three knees with medial-compartment osteoarthritis were retrospectively studied. Thirty-four knees with subluxated lateral joint and depression of the medial tibial plateau underwent TCVO and the rest underwent OWHTO. Among the 63 knees included, 27 knees with a pre-operative femorotibial angle (FTA) ≥ 185° were defined as severe varus (subgroup S, 15 in S group and 12 in S group). Lower limb alignment, intra-, and extra-articular congruency were evaluated according to the radiograph obtained before and 24 months after surgery. The visual analog scale (VAS) score and Hospital for Special Surgery (HSS) score were obtained to assess the clinical results. Opening angle and distance of the opening gap in each group were measured by intra-operative fluoroscopy.

Results: During the 2-year follow-up period, the mean HSS score increased from 70.3 to 81.4 in HTO group and 65.9 to 87.3 in TCVO group (p < 0.05). The mean VAS score decreased from 5.9 to 2.6 and 6.0 to 2.1, respectively (p < 0.01). Pre-operative FTA was restored to 172.9° in HTO group and 171.3° in TCVO group, and percentage of mechanical axis (%MA) was improved to 59.7% and 61.2%, respectively. Joint line convergence angle (JLCA) was slightly restored and medial tibial plateau depression (MTPD) was relatively the same before and after OWHTO, while these parameters improved greatly (from 6.4° to 1.2° and - 8.0° to 5.9°, p < 0.01) in TCVO group. More undercorrected knees were observed in S group than S group (58.3% and 13.3%, p < 0.05). Opening angle and distance of the opening gap were larger in TCVO group (19.1° and 14.0 mm) than those in OWHTO group (9.3° and 10.1 mm, p < 0.05).

Conclusion: Compared to OWHTO, TCVO had priority in treating advanced knee OA with intra-articular deformity. However, TCVO had a limited capacity to correct the varus angle. Besides, TCVO might be suitable for medial-compartment OA with a pre-operative FTA ≥ 185°.
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http://dx.doi.org/10.1186/s13018-021-02597-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278751PMC
July 2021

Clinical Features and Prognostic Factors of Children With Chronic Active Epstein-Barr Virus Infection: A Retrospective Analysis of a Single-Center.

J Pediatr 2021 Jul 11. Epub 2021 Jul 11.

Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Disease in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China, 100045.

Objective: To analyze the clinical characteristics, prognosis factors and risk factors of chronic active Epstein-Barr virus (EBV) infection in children.

Study Design: Observational analysis of baseline data and follow-up evaluation data of children with chronic active EBV infection in our center between January 1, 2016 and December 31, 2019, and were followed through June 30, 2020.

Results: There were 96 children with chronic active EBV infection, including 50 males and 46 females, with the median age of 6.7 years (range from 0.6-17.6 years) at diagnosis. The median follow-up time was 16.5 months. The three most common clinical manifestations were fever, lymph node enlargement, and hepatomegaly or splenomegaly. Thirty-three patients (36.3%) also had a diagnosis of hemophagocytic lymphohistiocytosis (HLH). EBV infected only T lymphocytes, NK cells, or both T- and NK-cell types in 15 (33.3%), 17 (37.8%), and 13 (28.9%), respectively. At the end of follow up, 26 children had died and 60 survived, 10 were lost to follow up. Generally, progression-free survival was 69.8% ± 2.4%. The level of 'IL-6 and IL-10' and the combination of 'younger age and lower pathologic grade' at diagnosis were independent prognostic factors by Cox regression analysis (P = .009 and 0.018, respectively).

Conclusions: Children with lower levels of IL-6 and IL-10, or with younger age and lower pathologic grades, generally had favorable outcomes at the terminal point of follow up, indicating better prognostic signs.
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http://dx.doi.org/10.1016/j.jpeds.2021.07.009DOI Listing
July 2021

Effect and safety of acupuncture on cerebrovascular reserve in patients with acute cerebral infarction: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jul;100(28):e26636

Department of Rehabilitation, Hotan District People's Hospital, Xinjiang, China.

Background: As far as we know, no evidence has been established to assess the effects of acupuncture for acute cerebral infarction patients. Therefore, this systematic review and meta-analysis will be conducted to assess the efficacy and safety of acupuncture on cerebrovascular reserve in patients with acute cerebral infarction.

Methods: On June 20, 2021, the authors will perform a preliminary search in the PubMed, Embase, and Scopus databases using the following keywords: "acupuncture," "acute cerebral infarction." We will also examine the Clinical Trials Registry for other ongoing and unpublished studies. The inclusion criteria included (1) patients with acute cerebral infarction, (2) patients who received acupuncture, and (3) studies assessed cerebrovascular reserve, breath-holding index, Barthel index, and adverse events. All English language randomized controlled trials published within the last 20 years were eligible for inclusion. Primary outcome measures in our study are cerebrovascular reserve, and secondary outcome measures include the breath-holding index, Barthel index, and adverse events. All outcomes are pooled on a random-effect model.

Results: The results of this research will be delivered in a peer-reviewed journal.

Osf Registration Number: 10.17605/OSF.IO/7M4BK.
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http://dx.doi.org/10.1097/MD.0000000000026636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284725PMC
July 2021

Zebrafish Model for Screening Antiatherosclerosis Drugs.

Oxid Med Cell Longev 2021 22;2021:9995401. Epub 2021 Jun 22.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198 Jiangsu, China.

This study is aimed at establishing a zebrafish model of AS, which can be applied for high-throughput screening anti-AS drugs. A zebrafish AS model was induced by high cholesterol diet (HCD) and lipopolysaccharide (LPS). In the early stage of modeling, HCD induced zebrafish to show some early symptoms similar to human AS, mainly cholesterol accumulation, vascular inflammation, lipid metabolism disorder, and oxidative stress. In addition to lipid metabolism disorders, LPS also induced the same symptoms. And when HCD and LPS exist at the same time, these AS symptoms in zebrafish become more severe. When the modeling time reached 45 days, HCD and LPS induce the formation of plaques in zebrafish blood vessels, and these plaques contain fibrous tissue and lipids, which are similar to human AS plaques. We also evaluated the efficacy of some anti-AS drugs (atorvastatin, aspirin, and vitamin C) through these zebrafish AS models. The results found that atorvastatin can significantly reduce the symptoms of AS induced by HCD and LPS, and aspirin and vitamins can significantly reduce the symptoms of AS induced by LPS. It is feasible to use zebrafish to establish an AS model, and the zebrafish AS model can be used for high-throughput screening of anti-AS drugs.
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http://dx.doi.org/10.1155/2021/9995401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245221PMC
June 2021

NOX4-Derived ROS Mediates TGF-1-Induced Metabolic Reprogramming during Epithelial-Mesenchymal Transition through the PI3K/AKT/HIF-1 Pathway in Glioblastoma.

Oxid Med Cell Longev 2021 27;2021:5549047. Epub 2021 Jun 27.

Department of Neurosurgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Current studies on tumor progression focus on the roles of cytokines in the tumor microenvironment (TME), and recent research shows that transforming growth factor-1 (TGF-1) released from TME plays a pivotal role in tumor development and malignant transformation. The alteration in cellular metabolism is a hallmark of cancer, which not only provides cancer cells with ATP for fuel cellular reactions, but also generates metabolic intermediates for the synthesis of essential cellular ingredients, to support cell proliferation, migration, and invasion. Interestingly, we found a distinct metabolic change during TGF-1-induced epithelial-mesenchymal transition (EMT) in glioblastoma cells. Indeed, TGF-1 participates in metabolic reprogramming, and the molecular basis is still not well understood. NADPH oxidases 4 (NOX4), a member of the Nox family, also plays a key role in the biological effects of glioblastoma. However, the relationship between NOX4, TGF-1, and cellular metabolic changes during EMT in glioblastoma remains obscure. Here, our findings demonstrated that TGF-1 upregulated NOX4 expression accompanied by reactive oxygen species (ROS) through Smad-dependent signaling and then induced hypoxia-inducible factor 1 (HIF-1) overexpression and nuclear accumulation resulting in metabolic reprogramming and promoting EMT. Besides, inhibition of glycolysis reversed EMT suggesting a causal relationship between TGF-1-induced metabolic changes and tumorigenesis. Moreover, TGF-1-induced metabolic reprogramming and EMT which modulated by NOX4/ROS were blocked when the phosphoinositide3-kinase (PI3K)/AKT/HIF-1 signaling pathways were inhibited. In conclusion, these suggest that NOX4/ROS induction by TGF-1 can be one of the main mechanisms mediating the metabolic reprogramming during EMT of glioblastoma cells and provide promising strategies for cancer therapy.
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http://dx.doi.org/10.1155/2021/5549047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257383PMC
June 2021

Relationship between periodontitis and microangiopathy in type 2 diabetes mellitus: a meta-analysis.

J Periodontal Res 2021 Jul 13. Epub 2021 Jul 13.

Xiyuan hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Objective: Whether periodontitis increases the risk of diabetic microangiopathy remains controversial. The present meta-analysis aims to investigate the relationship between periodontitis and diabetic microangiopathy in patients with type 2 diabetes mellitus.

Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, and WanFang data were searched without language restrictions. The methodological quality of the studies included was assessed using Newcastle-Ottawa Scale method, and meta-analysis was performed by Review Manager 5.3. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the risk of periodontitis for diabetic microangiopathy among patients with type 2 diabetes.

Results: Thirteen cross-sectional studies, covering 10 570 participants, were included in the present meta-analysis. The results demonstrated that periodontitis was associated with increased risk of type 2 diabetic microangiopathy (OR: 2.43, 95% CI: 1.65-3.56), diabetic retinopathy (OR: 4.33, 95% CI: 2.19-8.55), and diabetic nephropathy (OR: 1.75, 95% CI: 1.07-2.85), while periodontitis was not associated with diabetic neuropathy (OR: 0.99, 95% CI: 0.19-5.12). Subgroup analysis among the studies in Asian (OR: 3.06, 95% CI: 1.94-4.84) and North American (OR: 1.42, 95% CI: 1.08-1.86) populations confirmed the existed association between periodontitis and type 2 diabetic microangiopathy. The relationship still existed in groups with sample size larger than 500 (OR: 1.77, 95% CI: 1.34-2.34) and smaller than 500 (OR: 3.33, 95% CI: 1.38-8.03). A sensitivity analysis confirmed the stability of the results by excluding moderate quality studies or removing articles one after the other.

Conclusion: Current evidences have proved that periodontitis is associated with increased risk of diabetic microangiopathy in patients with type 2 diabetes mellitus. This conclusion may provide useful evidence for correlated clinical researches. PROSPERO registration number CRD42021247773.
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http://dx.doi.org/10.1111/jre.12916DOI Listing
July 2021

Acceleration of the bio-reduction of methyl orange by a magnetic and extracellular polymeric substance nanocomposite.

J Hazard Mater 2021 Jul 5;420:126576. Epub 2021 Jul 5.

Department of Environmental Engineering, College of Biology and the Environment, Nanjing Forestry University, Nanjing 210037, China; School of Environmental Science, Nanjing XiaoZhuang University, Nanjing 211171, China. Electronic address:

Extracellular electron transfer (EET) plays an important role in bio-reduction of environmental pollutants. Extracellular polymeric substances (EPS), a kind of biogenic macromolecule, contain functional groups responsible for acceleration of EET. In this study, azo dye-methyl orange (MO) was chosen as a model pollutant, and a FeO and EPS nanocomposite ([email protected]) was prepared to evaluate its promotion on the bio-reduction of MO. The flower-like core-shell configuration of [email protected] with a 12 nm of light layer of EPS was confirmed by TEM. The redox ability of EPS was well reserved on [email protected] by FTIR and electrochemical test. The application of [email protected] on sustained acceleration of MO decolorization were confirmed by batch experiments and anaerobic sequenced batch reactors. Due to biocompatibility of the biogenic shell, the as-prepared [email protected] exhibited low toxic to microorganisms by the Live/dead cell test. Moreover, negligible leaching of EPS under high concentration of various anions and less than 10% of EPS was released under extreme acidic and basic pH condition. The results of study provided a new preparation method of biological intimate and environmentally friendly redox mediators and suggested a feasible way for its use on bio-reduction of pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126576DOI Listing
July 2021

Development and validation of a survival model for esophageal adenocarcinoma based on autophagy-associated genes.

Bioengineered 2021 Dec;12(1):3434-3454

Division of Digestive Surgery, State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

Autophagy is a highly conserved catabolic process which has been implicated in esophageal adenocarcinoma (EAC). We sought to investigate the biological functions and prognostic value of autophagy-related genes (ARGs) in EAC. A total of 21 differentially expressed ARGs were identified between EAC and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were then applied for the differentially expressed ARGs in EAC, and the protein-protein interaction (PPI) network was established. Cox survival analysis and Lasso regression analysis were performed to establish a prognostic prediction model based on nine overall survival (OS)-related ARGs (CAPN1, GOPC, TBK1, SIRT1, ARSA, BNIP1, ERBB2, NRG2, PINK1). The 9-gene prognostic signature significantly stratified patient outcomes in The Cancer Genome of Atlas (TCGA)-EAC cohort and was considered as an independently prognostic predictor for EAC patients. Moreover, Gene set enrichment analysis (GSEA) analyses revealed several important cellular processes and signaling pathways correlated with the high-risk group in EAC. This prognostic prediction model was confirmed in an independent validation cohort (GSE13898) from The Gene Expression Omnibus (GEO) database. We also developed a nomogram with a concordance index of 0.78 to predict the survival possibility of EAC patients by integrating the risk signature and clinicopathological features. The calibration curves substantiated favorable concordance between actual observation and nomogram prediction. Last but not least, Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), a member of the prognostic gene signature, was identified as a potential therapeutic target for EAC patients. To sum up, we established and verified a novel prognostic prediction model based on ARGs which could optimize the individualized survival prediction in EAC.
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http://dx.doi.org/10.1080/21655979.2021.1946235DOI Listing
December 2021