Publications by authors named "Qin Zhou"

855 Publications

An injectable peptide hydrogel with excellent self-healing ability to continuously release salvianolic acid B for myocardial infarction.

Biomaterials 2021 Apr 29;274:120855. Epub 2021 Apr 29.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Drug-loaded hydrogels can improve blood supply and inhibit extracellular matrix degradation after myocardial infarction. However, due to the continual dynamic motion of cardiac tissue, the hydrogel structure cannot be reconstructed in time, causing accelerated degradation and drug burst release. Here, a novel, superior, self-healing elastin-mimic peptide hydrogel (EMH) was fabricated for the local delivery of salvianolic acid B (SaB). The self-healing ability of EMH is enhanced by SaB-loaded polydopamine nanoparticles (SaB-PDA). In vitro, the pre-hydrogel (SaB-PDA/pre-EMH) is endowed with excellent biocompatibility and a low viscosity, making it suitable for intramyocardial injection. Once injected into the myocardial infarction (MI) region, SaB-PDA/pre-EMH can form SaB-PDA/EMH with great mechanical strength under the action of upregulated transglutaminase (TGase) in heart tissue post-MI. The superior self-healing ability of SaB-PDA/EMH allows for an increase in retention time in the beating ventricular wall. Therefore, with long-term release of SaB, SaB-PDA/EMH can inhibit ventricular remodeling and promote angiogenesis for MI treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120855DOI Listing
April 2021

Characterization of Aroma-Active Compounds in Northern Highbush Blueberries "Bluecrop" ( "Bluecrop") and "Elliott" ( "Elliott") by Gas Chromatography-Olfactometry Dilution Analysis and Odor Activity Value.

J Agric Food Chem 2021 May 11. Epub 2021 May 11.

Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331, United States.

Aroma-active compounds in northern highbush blueberries "Bluecrop" ( "Bluecrop") and "Elliott" ( "Elliott") were isolated using solvent extraction followed by solvent-assisted flavor evaporation. The aroma-active compounds were compared by aroma extract dilution analysis (AEDA) on a polar and a chiral column and odor activity values (OAVs). The results showed that both cultivars had similar aroma-active compounds, but the flavor dilution (FD) factors and OAV values varied, responsible for the subtle aroma differences. AEDA (FD ≥ 64) suggested that the important aroma-active compounds in both cultivars could be ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, (Z)-3-hexenal, 1-octen-3-one, (Z)-3-hexen-1-ol, methional, linalool, (E,Z)-2,6-nonadienal, 2-methylbutanoic acid, α-terpineol, (E,E)-2,4-nonadienal, β-damascenone, geraniol, geranyl acetone, -cresol, eugenol, and vanillin. Different isomers can have different sensory thresholds and attributes. Enantiomer analysis revealed that although S-(+)-linalool was dominant in blueberry, R-(-)-linalool had a higher FD value and OAVs than that of the (S)-isomer. The S-(-)-α-terpineol was slightly elevated than R-(+)-α-terpineol in both cultivars.
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http://dx.doi.org/10.1021/acs.jafc.1c01044DOI Listing
May 2021

PINK1 contained in huMSC-derived exosomes prevents cardiomyocyte mitochondrial calcium overload in sepsis via recovery of mitochondrial Ca efflux.

Stem Cell Res Ther 2021 May 6;12(1):269. Epub 2021 May 6.

Chongqing Key Laboratory of Pediatrics, Chongqing, People's Republic of China.

Background: Sepsis is a systemic inflammatory response to a local severe infection that may lead to multiple organ failure and death. Previous studies have shown that 40-50% of patients with sepsis have diverse myocardial injuries and 70 to 90% mortality rates compared to 20% mortality in patients with sepsis without myocardial injury. Therefore, uncovering the mechanism of sepsis-induced myocardial injury and finding a target-based treatment are immensely important.

Objective: The present study elucidated the mechanism of sepsis-induced myocardial injury and examined the value of human umbilical cord mesenchymal stem cells (huMSCs) for protecting cardiac function in sepsis.

Methods: We used cecal ligation and puncture (CLP) to induce sepsis in mice and detect myocardial injury and cardiac function using serological markers and echocardiography. Cardiomyocyte apoptosis and heart tissue ultrastructure were detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) and transmission electron microscopy (TEM), respectively. Fura-2 AM was used to monitor Ca uptake and efflux in mitochondria. FQ-PCR and Western blotting detected expression of mitochondrial Ca distribution regulators and PTEN-induced putative kinase 1 (PINK1). JC-1 was used to detect the mitochondrial membrane potential (Δψm) of cardiomyocytes.

Results: We found that expression of PINK1 decreased in mouse hearts during sepsis, which caused cardiomyocyte mitochondrial Ca efflux disorder, mitochondrial calcium overload, and cardiomyocyte injury. In contrast, we found that exosomes isolated from huMSCs (huMSC-exo) carried Pink1 mRNA, which could be transferred to recipient cardiomyocytes to increase PINK1 expression. The reduction in cardiomyocyte mitochondrial calcium efflux was reversed, and cardiomyocytes recovered from injury. We confirmed the effect of the PINK1-PKA-NCLX axis on mitochondrial calcium homeostasis in cardiomyocytes during sepsis.

Conclusion: The PINK1-PKA-NCLX axis plays an important role in mitochondrial calcium efflux in cardiomyocytes. Therefore, PINK1 may be a therapeutic target to protect cardiomyocyte mitochondria, and the application of huMSC-exo is a promising strategy against sepsis-induced heart dysfunction.
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http://dx.doi.org/10.1186/s13287-021-02325-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101124PMC
May 2021

Study on the Appropriate Timing of Postoperative Adaptive Radiotherapy for High-Grade Glioma.

Cancer Manag Res 2021 28;13:3561-3572. Epub 2021 Apr 28.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Purpose: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma.

Methods: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT/MRI, CT/MRI, CT/MRI, and CT/MRI) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan, plan, plan and plan) were made. The dose of the initial plan (plan) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan and plan) and by superimposing the doses to obtain the ART plans (plan and plan), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans.

Results: Compared with the projection plan, the D to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D/D to the brainstem, optic chiasm and pituitary, as well as the V, V, V and V to the normal brain decreased. The D to the pituitary and optic chiasm as well as the V, V, V and V to the normal brain in plan were lower than those in plan, while the CI to the PTV was higher than that in plan. The TCP of the PTV in plan was higher than that in plan.

Conclusion: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.
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http://dx.doi.org/10.2147/CMAR.S300094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089024PMC
April 2021

Impact of acyl-homoserine lactones on the response of nitrogen cycling in sediment to florfenicol stress.

Sci Total Environ 2021 Apr 24;785:147294. Epub 2021 Apr 24.

National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China. Electronic address:

Antibiotic residuals disrupt environmental microbial metabolism and can alter the nitrogen cycle. Quorum sensing has both inter- and intra-species effects that are directly related to the population densities necessary for microbial nitrogen cycling. Here, we explored how acyl-homoserine lactones (AHLs) can change the response of nitrogen cycling to florfenicol in sediments. AHLs might promote microbial reproduction in sediment under florfenicol stress. The relative abundances of Proteobacteria and Euryarchaeota in the antibiotic and AHL treatment groups were higher than those in the control group. AHLs reduced the effects of antibiotics on the abundance of Nitrospira at sampling times of 3d, 10d, and 20d. In the annotation results, nitrate reductase showed the highest abundance, followed by nitrite reductase, nitrogenase, nitric oxide (NO) reductase, nitrous oxide reductase, and ammonia monooxygenase. The abundances of these genes have changed in response to pressure by florfenicol and the addition of AHLs. We also found significant associations between the nitrogen cycle-related functional genes and dominant genera. In particular, glutamate metabolic enzymes and nitrate/nitrite transporters were the primary participants in correlation. Florfenicol can rapidly alter microbial community structures in sediments, affect the functional diversity of microorganisms, and hinder the nitrogen cycle. The response of microorganisms to florfenicol was regulated by the addition of AHLs. This process might alter the use and production of nitrogenous substances in the environment by functional communities in sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147294DOI Listing
April 2021

Bevacizumab in advanced endometrial cancer.

Gynecol Oncol 2021 Apr 21. Epub 2021 Apr 21.

Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objective: Prospective data have demonstrated the efficacy of bevacizumab monotherapy in the treatment of advanced endometrial cancer. Bevacizumab is used off-label, and real-world data regarding the role of bevacizumab in endometrial cancer treatment are scant. In this largest single-institution retrospective study of its kind, we report our experience with bevacizumab monotherapy in the treatment of advanced/recurrent endometrial cancer.

Methods: All eligible patients (n = 101) had histologically confirmed endometrial cancer and were treated with bevacizumab at our institution from 2004 to 2017. Demographic data and tumor characteristics were obtained through chart review. Primary objective was response to therapy determined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Results: Analysis included 13 grade 1/2 endometrioid, 15 grade 3 endometrioid, 44 serous, 8 carcinosarcoma, and 21 other/mixed histologies. No patients achieved complete (CR) or partial (PR) responses; 19 achieved stable disease (SD). The clinical benefit rate (CBR; CR + PR + SD) was 19% (95% CI: 12-28%). The CBRs were 7%, 17%, 21%, and 23% for patients with 1, 2, 3, and ≥ 4 prior treatment lines. Median PFS ranged from 2.6 months (2 lines) to 4.9 months (≥4 lines). The 3-year OS rate was 58% (95% CI: 47-67%). The median OS was 3.4 years (95% CI: 2.9-4.2), ranging from 2.5 years (2 lines) to 4.5 years (≥4 lines). The most common treatment-related adverse event was hypertension; 35 (78%) of 45 were grade 1 or 2.

Conclusions: In heavily pretreated advanced endometrial cancer, bevacizumab was associated with modest clinical efficacy and remains a viable palliative option in this setting.
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http://dx.doi.org/10.1016/j.ygyno.2021.04.016DOI Listing
April 2021

An Adapted Neural-Fuzzy Inference System Model Using Preprocessed Balance Data to Improve the Predictive Accuracy of Warfarin Maintenance Dosing in Patients After Heart Valve Replacement.

Cardiovasc Drugs Ther 2021 Apr 20. Epub 2021 Apr 20.

Department of Evidence-Based Medicine and Clinical epidemiology, West China Hospital, Sichuan University, Chengdu, China.

Background: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR).

Methods: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses).

Results: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding.

Conclusions: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.
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http://dx.doi.org/10.1007/s10557-021-07191-1DOI Listing
April 2021

Reciprocal regulation of RIG-I and XRCC4 connects DNA repair with RIG-I immune signaling.

Nat Commun 2021 04 12;12(1):2187. Epub 2021 Apr 12.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

The RNA-sensing pathway contributes to type I interferon (IFN) production induced by DNA damaging agents. However, the potential involvement of RNA sensors in DNA repair is unknown. Here, we found that retinoic acid-inducible gene I (RIG-I), a key cytosolic RNA sensor that recognizes RNA virus and initiates the MAVS-IRF3-type I IFN signaling cascade, is recruited to double-stranded breaks (DSBs) and suppresses non-homologous end joining (NHEJ). Mechanistically, RIG-I interacts with XRCC4, and the RIG-I/XRCC4 interaction impedes the formation of XRCC4/LIG4/XLF complex at DSBs. High expression of RIG-I compromises DNA repair and sensitizes cancer cells to irradiation treatment. In contrast, depletion of RIG-I renders cells resistant to irradiation in vitro and in vivo. In addition, this mechanism suggests a protective role of RIG-I in hindering retrovirus integration into the host genome by suppressing the NHEJ pathway. Reciprocally, XRCC4, while suppressed for its DNA repair function, has a critical role in RIG-I immune signaling through RIG-I interaction. XRCC4 promotes RIG-I signaling by enhancing oligomerization and ubiquitination of RIG-I, thereby suppressing RNA virus replication in host cells. In vivo, silencing XRCC4 in mouse lung promotes influenza virus replication in mice and these mice display faster body weight loss, poorer survival, and a greater degree of lung injury caused by influenza virus infection. This reciprocal regulation of RIG-I and XRCC4 reveals a new function of RIG-I in suppressing DNA repair and virus integration into the host genome, and meanwhile endues XRCC4 with a crucial role in potentiating innate immune response, thereby helping host to prevail in the battle against virus.
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http://dx.doi.org/10.1038/s41467-021-22484-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041803PMC
April 2021

A sequential guide to identify neonates with low bacterial meningitis risk: a multicenter study.

Ann Clin Transl Neurol 2021 May 9;8(5):1132-1140. Epub 2021 Apr 9.

Department of Neonatology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: To derive and validate a predictive algorithm integrating clinical and laboratory parameters to stratify a full-term neonate's risk level of having bacterial meningitis (BM).

Methods: A multicentered dataset was categorized into derivation (689 full-term neonates aged ≤28 days with a lumbar puncture [LP]) and external validation (383 neonates) datasets. A sequential algorithm with risk stratification for neonatal BM was constructed.

Results: In the derivation dataset, 102 neonates had BM (14.8%). Using stepwise regression analysis, fever, infection source absence, neurological manifestation, C-reactive protein (CRP), and procalcitonin were selected as optimal predictive sets for neonatal BM and introduced to a sequential algorithm. Based on the algorithm, 96.1% of BM cases (98 of 102) were identified, and 50.7% of the neonates (349 of 689) were classified as low risk. The algorithm's sensitivity and negative predictive value (NPV) in identifying neonates at low risk of BM were 96.2% (95% CI 91.7%-98.9%) and 98.9% (95% CI 97.6%-99.6%), respectively. In the validation dataset, sensitivity and NPV were 95.9% (95% CI 91.0%-100%) and 98.8% (95% CI 97.7%-100%).

Interpretation: The sequential algorithm can risk stratify neonates for BM with excellent predictive performance and prove helpful to clinicians in LP-related decision-making.
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http://dx.doi.org/10.1002/acn3.51356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108426PMC
May 2021

Prevalence and coprevalence of modifiable risk factors for upper digestive tract cancer among residents aged 40-69 years in Yangzhong city, China: a cross-sectional study.

BMJ Open 2021 Apr 7;11(4):e042006. Epub 2021 Apr 7.

Department of Oncology, 923rd Hospital of PLA, Hangzhou, China.

Objectives: To describe the prevalence of modifiable risk factors for upper digestive tract cancer (UDTC) and its coprevalence, and investigate relevant influencing factors of modifiable UDTC risk factors coprevalence among residents aged 40-69 years in Yangzhong city, China.

Design: Cross-sectional study.

Participants: A total of 21 175 participants aged 40-69 years were enrolled in the study. 1962 subjects were excluded due to missing age, marital status or some other selected information. Eventually, 19 213 participants were available for the present analysis.

Main Outcomes Measures: Prevalence and coprevalence of eight modifiable UDTC risk factors (overweight or obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food) were analysed.

Results: The prevalence of overweight/obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food in this study was 45.3%, 24.1%, 16.2%, 66.1%, 94.5%, 68.1%, 36.0% and 88.4%, respectively. Nearly all (99.9%) participants showed one or more UDTC risk factors, 98.6% of the participants showed at least two risk factors, 92.2% of the participants had at least three risk factors and 69.7% of the participants had four or more risk factors. Multivariate logistic regression analysis revealed that men, younger age, single, higher education, higher annual family income and smaller household size were more likely to present modifiable UDTC risk factors coprevalence.

Conclusions: The prevalence and coprevalence of modifiable UDTC risk factors are high among participants in Yangzhong city. Extra attention must be paid to these groups who are susceptible to risk factors coprevalence during screening progress. Relative departments also need to make significant public health programmes that aim to decrease modifiable UDTC risk factors coprevalence among residents aged 40-69 years from high-risk areas of UDTC.
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http://dx.doi.org/10.1136/bmjopen-2020-042006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031018PMC
April 2021

The lncRNA PVT1/miR-590-5p/FSTL1 axis modulates the proliferation and migration of airway smooth muscle cells in asthma.

Autoimmunity 2021 May 7;54(3):138-147. Epub 2021 Apr 7.

Department of Pediatrics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, P.R. China.

Objective: Asthma is a prevalent chronic inflammatory airway disease that is characterised by airway remodelling and airway hyperresponsiveness. Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) contribute to airway remodelling in asthma. However, the molecular mechanism underlying an increased ASMC mass in asthma remains elusive. Herein, we aimed at investigating the regulation of lncRNA PVT1 on ASMCs and focussing on the mechanism in the proliferation and migration.

Methods: Expression levels of lncRNA PVT1 and miR-590-5p in the serum collected from 24 children with asthma and 10 control children were determined by qRT-PCR. ASMCs proliferation and migration prior to and post platelet-derived growth factor subunit B (PDGF-BB) stimulation were examined by CCK-8 test and transwell assay. Dual-luciferase reporter assay was performed to determine miR-590-5p interaction with lncRNA PVT1 and follistatin-like 1 (FSTL1). Expression of lncRNA PVT1, miR-590-5p, FSTL1, C-Myc, cyclin D1, and cyclin-dependent kinase 1 (CDK1) was tested by quantitative real-time PCR (qRT-PCR) and immunoblotting analysis.

Results: The expression level of lncRNA PVT1 was higher but the expression level of miR-590-5p was lower in the serum of children with asthma than in control children. The expression level of lncRNA PVT1 was negatively correlated with the expression level of miR-590-5p in asthma. LncRNA PVT1 was upregulated upon PDGF-BB stimulation. LncRNA PVT1 knockdown by its specific shRNA repressed PDGF-BB-induced promotion of proliferation and migration in ASMCs and triggered an elevated miR-590-5p along with declined C-Myc, cyclin D1, and CDK1. The effects of lncRNA PVT1 knockdown on PDGF-BB-induced ASMCs were lost upon miR-590-5p inhibition. MiR-590-5p targeted FSTL1 gene and declined its expression, thus suppressing ASMC proliferation and migration following PDGF-BB stimulation and downregulating C-Myc, cyclin D1, and CDK1 expressions. The effects of miR-590-5p on PDGF-BB-induced ASMCs were lost upon FSTL1 overexpression.

Conclusion: These results support the notion that the lncRNA PVT1/miR-590-5p/FSTL1 axis modulates ASMCs proliferation and migration following PDGF-BB stimulation, providing a potential therapeutic target to attenuate airway remodelling in asthma.
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http://dx.doi.org/10.1080/08916934.2021.1897977DOI Listing
May 2021

miR156/157 targets SPLs to regulate flowering transition, plant architecture and flower organ size in petunia.

Plant Cell Physiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Botany, Guangzhou Institute of Forestry and Landscape Architecture, Guangzhou 510405, China.

miR156/157 plays multiple pivotal roles during plant growth and development. In this study, we identified 11 miR156- and 5 miR157-encoding loci from the genome of P. axillaris and P. inflata, designated as PaMIR0156/157s and PiMIR0156/157s, respectively. qPCR analysis indicated that PhmiR156/157 was expressed predominantly in cotyledons, germinating seeds, flower buds, young fruits, and seedlings. PhmiR156/157 levels declined in shoot apical buds and leaves of petunia before flowering as the plant ages, moreover, the temporal expression patterns of most miR156/157-targeted PhSPLs were complementary to that of PhmiR156/157. Ectopic expression of PhMIR0157a in Arabidopsis and petunia resulted in delayed flowering, dwarf plant stature, increased branches, and reduced organ size. However, PhMIR0156f-overexpressing Arabidopsis and petunia plants showed only delayed flowering. In addition, down-regulation of PhmiR156/157 level by overexpressing STTM156/157 led to higher plant, less branches, longer internodes, and precocious flowering. qPCR analysis indicated that PhmiR156/157 modulates these traits mainly via down-regulating their PhSPL targets and subsequently decreasing the expression of flowering regulatory genes. Our results demonstrated that PhmiR156/157-PhSPL module has conserved but also divergent functions in the growth and development, which will help us deciphering the genetic basis for improvement of flower transition, plant architecture and organ development in petunia.
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http://dx.doi.org/10.1093/pcp/pcab041DOI Listing
March 2021

Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells.

Front Cell Dev Biol 2021 9;9:644667. Epub 2021 Mar 9.

Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (hiPSC-CMs) are a promising cell source for disease modeling, myocardial regeneration, and drug assessment. However, hiPSC-CMs have certain immature fetal CM-like properties that are different from the characteristics of adult CMs in several aspects, including cellular structure, mitochondrial function, and metabolism, thus limiting their applications. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing protein kinase involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in cardiomyocytes. This study investigated the effects of AMPK on the maturation of hiPSC-CMs. Activation of AMPK in hiPSC-CMs significantly increased the expression of CM-specific markers and resulted in a more mature myocardial structure compared to that in the control cells. We found that activation of AMPK improved mitochondrial oxidative phosphorylation (OxPhos) and the oxygen consumption rate (OCR). Additionally, our data demonstrated that activation of AMPK increased mitochondrial fusion to promote the maturation of mitochondrial structure and function. Overall, activation of AMPK is an effective approach to promote hiPSC-CMs maturation, which may enhance the utility of hiPSC-CMs in clinical applications.
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http://dx.doi.org/10.3389/fcell.2021.644667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985185PMC
March 2021

Dicer1 Promotes Colon Cancer Cell Invasion and Migration Through Modulation of tRF-20-MEJB5Y13 Expression Under Hypoxia.

Front Genet 2021 8;12:638244. Epub 2021 Mar 8.

Department of Colorectal Surgery, 4th Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Hypoxia plays a key role in colorectal cancer (CRC) metastasis, but its underlying mechanism remains largely unknown. Dicer1, an RNase, has been considered as a tumor regulator in many tumors. However, whether Dicer1 affects CRC progression under hypoxia remains uncertain. In this study, we found that Dicer1 expression was induced by hypoxia in CRC cells and it mediates hypoxia-induced CRC cell progression. Furthermore, we found that the expression of tRF-20-MEJB5Y13, a small non-coding RNA derived from tRNA, was increased under hypoxic conditions, and its upregulation by Dicer1 resulted in hypoxia-induced CRC cell invasion and migration. These results advance the current understanding of the role of Dicer1 in regulating hypoxia signals and provide a new pathway for the development of therapeutic interventions for inhibiting cancer progression.
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http://dx.doi.org/10.3389/fgene.2021.638244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982525PMC
March 2021

NRF2 is required for structural and metabolic maturation of human induced pluripotent stem cell-derived ardiomyocytes.

Stem Cell Res Ther 2021 Mar 24;12(1):208. Epub 2021 Mar 24.

Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, Box 136, No. 3 Zhongshan RD, Yuzhong district, Chongqing, 400014, People's Republic of China.

Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for regenerative medicine and in drugs screening. Despite displaying key cardiomyocyte phenotypic characteristics, they more closely resemble fetal/neonatal cardiomyocytes and are still immature; these cells mainly rely on glucose as a substrate for metabolic energy, while mature cardiomyocytes mainly employ oxidative phosphorylation of fatty acids. Studies showed that the alteration of metabolism pattern from glycolysis to oxidative phosphorylation improve the maturity of hiPSC-CMs. As a transcription factor, accumulating evidences showed the important role of NRF2 in the regulation of energy metabolism, which directly regulates the expression of mitochondrial respiratory complexes. Therefore, we hypothesized that NRF2 is involved in the maturation of hiPSC-CMs.

Methods: The morphological and functional changes related to mitochondria and cell maturation were analyzed by knock-down and activation of NRF2.

Results: The results showed that the inhibition of NRF2 led to the retardation of cell maturation. The activation of NRF2 leads to a more mature hiPSC-CMs phenotype, as indicated by the increase of cardiac maturation markers, sarcomere length, calcium transient dynamics, the number and fusion events of mitochondria, and mitochondrial respiration. Bioinformatics analysis showed that in addition to metabolism-related genes, NRF2 also activates the expression of myocardial ion channels.

Conclusions: These findings indicated that NRF2 plays an important role in the maturation of hiPSC-CMs. The present work provides greater insights into the molecular regulation of hiPSC-CMs metabolism and theoretical basis in drug screening, disease modeling, and alternative treatment.
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http://dx.doi.org/10.1186/s13287-021-02264-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992990PMC
March 2021

Aspirin Use and Risk of Breast Cancer: A Meta-analysis of Observational Studies from 1989 to 2019.

Clin Breast Cancer 2021 Feb 17. Epub 2021 Feb 17.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Anhui, China; Center for Evidence-Based Practice, Anhui Medical University, Anhui, China. Electronic address:

Background: Some evidence shows that aspirin can reduce the morbidity and mortality of different cancers, including breast cancer. Aspirin has become a new focus of cancer prevention and treatment research at present, however, clinical studies found conflicting conclusions of its anticancer characteristics.

Materials And Methods: A systematic literature search was performed in 8 electronic databases. The pooled relative risk (RR) with 95% confidence interval (CI) was calculated using the random effects model to estimate the effect of aspirin on breast cancer.

Results: Forty-two published articles with 99,769 patients were identified. The meta-analysis showed a significant decrease in breast cancer risk with aspirin use (RR, 0.92; 95% CI, 0.89-0.96; I = 72%). Aspirin use decreased the risk of hormone receptor-positive tumors (estrogen receptor [ER]-positive RR, 0.89; 95% CI, 0.82-0.97; I=54%; progesterone receptor [PR]-positive RR, 0.86; 95% CI, 0.78-0.95; I=32%; ER- and PR-positive RR, 0.92; 95% CI, 0.85-1.00; I=45%) and reduced the risk of breast cancer in postmenopausal women (RR, 0.92; 95% CI, 0.86-0.98; I=59%). Further analysis showed that for the in situ breast cancer, regular-dose and more than 3 years use of aspirin were associated with the reduced risk of breast cancer.

Conclusion: This meta-analysis suggested that aspirin may reduce the overall risk of breast cancer, reduce the risk of breast cancer in postmenopausal women, hormone receptor-positive tumors, and in situ breast cancer. Larger, multicenter clinical studies are needed to find the optimal dose range, frequency, and duration of the aspirin use to explore the best benefit-risk ratio.
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http://dx.doi.org/10.1016/j.clbc.2021.02.005DOI Listing
February 2021

Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice.

J Inflamm Res 2021 10;14:803-816. Epub 2021 Mar 10.

Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China.

Background: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.

Methods: WT, Nrf2 mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.

Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2 neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.

Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
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http://dx.doi.org/10.2147/JIR.S303105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957230PMC
March 2021

The Deubiquitinating Enzyme UCHL1 Induces Resistance to Doxorubicin in HER2+ Breast Cancer by Promoting Free Fatty Acid Synthesis.

Front Oncol 2021 24;11:629640. Epub 2021 Feb 24.

Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

Ubiquitin C-terminal hydrolase L1 (UCHL1), which is a deubiquitinating enzyme, is known to play a role in chemoresistance in cancers. However, its potential roles and mechanisms in the chemoresistance of breast cancer (BC) remain unclear. In this study, we examined its expression in patients with BC and employed Kaplan-Meier analysis and the log-rank test for survival analyses. It was found that up-regulated UCHL1 expression was positively associated with both chemoresistance and poor prognosis, especially in patients with HER2+ BC. Moreover, UCHL1 expression was elevated in HER2+ BC cells (SK-BR-3 and BT474). Similarly, doxorubicin (DOX)-resistant BC cells (MCF-7/DOX) had higher UCHL1 levels than MCF-7 cells. CCK-8 assay showed that BC cells with higher UCHL1 levels were more resistant to DOX. Furthermore, by inhibiting UCHL1 in BC cells with elevated UCHL1 expression, we demonstrated that UCHL1 promoted DOX-resistance in BC. Mechanistically, UCHL1 probably promoted DOX-resistance of BC by up-regulating free fatty acid (FFA) synthesis, as exhibited by reduced FFA synthase expression and resurrected DOX-sensitivity upon UCHL1 inhibition. Overall, UCHL1 up-regulation is associated with DOX-resistance and poor prognosis in patients with HER2+ BC. UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC.
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http://dx.doi.org/10.3389/fonc.2021.629640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943833PMC
February 2021

Outcomes of incidentally detected ovarian cancers diagnosed at time of risk-reducing salpingo-oophorectomy in BRCA mutation carriers.

Gynecol Oncol 2021 May 10;161(2):521-526. Epub 2021 Mar 10.

Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA; Robert and Kate Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; HOPe Directorate, St. James's Hospital, Dublin, Ireland. Electronic address:

Objective: Prior data suggested that women with incidentally detected occult invasive ovarian cancer (OIOC) at the time of risk-reducing salpingo-oophorectomy (RRSO) for BRCA mutation may have poorer prognoses than would be expected based on disease stage. We sought to evaluate prevalence and outcomes of patients with OIOC in a tertiary referral center.

Methods: Patients with BRCA mutation undergoing RRSO from 01/2005 to 05/2017 were identified, and their records reviewed. Women with incidentally detected OIOC were included; those with clinical features raising preoperative suspicion for malignancy were excluded.

Results: 548 patients with BRCA mutation who underwent RRSO were identified. 26 (4.7%) had an OIOC (median age 55 years; range 42-75); 15(58%) patients, BRCA1; 9(34%), BRCA2; 2(8%) had a mutation in both genes. All OIOCs were high-grade serous: 10 (38%) Stage I; 8 (31%) Stage II; 8(31%) Stage III. 24(92%) patients received adjuvant platinum/taxane therapy. Of Stage III patients, 4 (50%) were identified intraoperatively; the remaining 4 (50%) had microscopic nodal disease on final pathology only. At median follow-up of 67.3 months (28-166) no Stage I patients have recurred; 2 Stage II and 6 Stage III patients recurred. 5-year progression-free survival (PFS) was 72% (95%CI, 50.2-85.7%); median PFS for the cohort was 129 months (95%CI, 75.3-not estimable). 5-year disease-specific survival (DSS) was 96% (95%CI, 76-99%); median DSS not reached.

Conclusion: Consistent with prior reports, almost 5% of patients had an OIOC at RRSO. The majority with early-stage disease had excellent PFS and DSS outcomes, as would be expected based on disease stage.
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http://dx.doi.org/10.1016/j.ygyno.2021.02.006DOI Listing
May 2021

DOCK7 protects against replication stress by promoting RPA stability on chromatin.

Nucleic Acids Res 2021 04;49(6):3322-3337

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.

RPA is a critical factor for DNA replication and replication stress response. Surprisingly, we found that chromatin RPA stability is tightly regulated. We report that the GDP/GTP exchange factor DOCK7 acts as a critical replication stress regulator to promote RPA stability on chromatin. DOCK7 is phosphorylated by ATR and then recruited by MDC1 to the chromatin and replication fork during replication stress. DOCK7-mediated Rac1/Cdc42 activation leads to the activation of PAK1, which subsequently phosphorylates RPA1 at S135 and T180 to stabilize chromatin-loaded RPA1 and ensure proper replication stress response. Moreover, DOCK7 is overexpressed in ovarian cancer and depleting DOCK7 sensitizes cancer cells to camptothecin. Taken together, our results highlight a novel role for DOCK7 in regulation of the replication stress response and highlight potential therapeutic targets to overcome chemoresistance in cancer.
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http://dx.doi.org/10.1093/nar/gkab134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034614PMC
April 2021

Plasmodium infection inhibits triple negative 4T1 breast cancer potentially through induction of CD8 T cell-mediated antitumor responses in mice.

Biomed Pharmacother 2021 Jun 3;138:111406. Epub 2021 Mar 3.

The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, 1st Yixueyuan Road, 400016 Chongqing, China. Electronic address:

We previously reported that Plasmodium infection promotes antitumor immunity in a murine Lewis lung cancer. In this study, we investigated the effects of Plasmodium infection on the tumor inhibition and antitumor CD8 T cell responses in a murine triple negative breast cancer (TNBCA) model. The results showed that Plasmodium infection significantly inhibited tumor growth, and increased the survival rate of the tumor-bearing mice. Both effector and memory CD8 T cells were increased in peripheral blood and tumor-draining lymph node (DLN) in the infected mice. The co-stimulatory (CD40L, GITR and OX-40) and co-inhibitory (PD-1, CTLA-4, TIM-3, LAG3) immune checkpoints were up-regulated on CD8 T cells in infected mice. Importantly, Py induced remarkable effects on the infiltration of CD8 T cells in the tumor and granzym B CD8 T cells in tumor-bearing mice while not in tumor-free mice. In summary, the results suggested that the effects of Plasmodium infection on murine 4T1 breast cancer might be related to the induction of CD8 T cell-mediated antitumor immune responses. This finding may provide a novel strategy for the treatment of triple negative breast cancer.
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http://dx.doi.org/10.1016/j.biopha.2021.111406DOI Listing
June 2021

Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats.

Front Pharmacol 2021 16;12:636154. Epub 2021 Feb 16.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Hyperuricemia is an independent risk factor for renal damage and promotes the progression of chronic kidney disease. In this study, we investigated the effect of I-BET151, a small-molecule inhibitor targeting the bromodomain and extraterminal (BET) proteins, on the development of hyperuricemic nephropathy (HN), and the mechanisms involved. Expression levels of bromodomain-containing protein 2 and 4, but not 3 were increased in the kidney of rats with HN; administration of I-BET151 effectively prevented renal dysfunction, decreased urine microalbumin, and attenuated renal fibrosis as indicated by reduced activation of renal interstitial fibroblasts and expression of fibronectin and collagen I in HN rats. Mechanistic studies show that I-BET151 treatment inhibited transition of renal epithelial cells to a mesenchymal cell type as evidenced by preservation of E-cadherin and reduction of vimentin expression. This was coincident with reduced expression of TGF-β1 and dephosphorylation of Smad3 and ERK1/2. I-BET151 was also effective in inhibiting phosphorylation of NF-κB, expression of multiple cytokines and chemokines, and infiltration of macrophages to the injured kidney. Although there were increased serum levels of uric acid and xanthine oxidase, an enzyme that catalyzes production of uric acid, and decreased expression of renal organic anion transporter 1 and 3 that promote urate excretion in the model of HN, and reduced expression levels of urine uric acid, I-BET151 treatment did not affect these responses. Collectively, our results indicate that I-BET151 alleviates HN by inhibiting epithelial to mesenchymal transition and inflammation in association with blockade of TGF-β, ERK1/2 and NF-κB signaling.
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http://dx.doi.org/10.3389/fphar.2021.636154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921804PMC
February 2021

The incidence trends of liver cirrhosis caused by nonalcoholic steatohepatitis via the GBD study 2017.

Sci Rep 2021 Mar 4;11(1):5195. Epub 2021 Mar 4.

Clinical Nursing Teaching and Research Section, Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Nonalcoholic steatohepatitis (NASH) has rapidly become the most common cause of chronic liver diseases. We aimed to explore the incidence and distribution characteristics of NASH by sex, region and sociodemographic index (SDI). We collected data, including sex and region, on NASH-related liver cirrhosis from the 2017 GBD study. The age-standardized incidence rates (ASRs) and estimated annual percentage changes (EAPCs) were used to estimate the incidence trend and distribution characteristics. Globally, the incidence of liver cirrhosis caused by NASH increased from 178,430 cases in 1990 to 367,780 cases in 2017, an increase of approximately 105.56%. The ASR of NASH increased by an average of 1.35% per year (95% CI 1.28-1.42). Meanwhile, large differences in the ASR and the EAPC were observed across regions. The middle-high SDI region had the highest increase among all five SDI regions, followed by middle SDI region. In addition, Eastern Europe, Andean Latin America and Central Asia showed a more significant growth trend of ASR. In contrast, the high SDI region demonstrated the slowest increasing trend of ASR, and the high-income Asia Pacific demonstrated a decreasing trend among the 21 regions. Liver cirrhosis has caused a huge and rising health burden in many countries and regions. In addition, with the growth of obesity, population and aging, NASH might replace viral hepatitis as the most important cause of liver cirrhosis in the near future. Therefore, appropriate interventions are needed in coming decades to realize early diagnosis and prevention of NASH-related liver cirrhosis.
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http://dx.doi.org/10.1038/s41598-021-84577-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933440PMC
March 2021

A boy with purpura on the legs.

BMJ 2021 03 4;372:n329. Epub 2021 Mar 4.

Kidney Disease Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, China

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http://dx.doi.org/10.1136/bmj.n329DOI Listing
March 2021

Clinical Efficacy and Safety of Propranolol in the Prevention and Treatment of Retinopathy of Prematurity: A Meta-Analysis of Randomized Controlled Trials.

Front Pediatr 2021 10;9:631673. Epub 2021 Feb 10.

Department of Pediatrics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

To perform a meta-analysis of randomized controlled trials verifying clinical efficacy and safety of propranolol in pre-term newborns with retinopathy of prematurity (ROP). We searched the literature databases (Pubmed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, VIP, CBM) for publications before August 10, 2020, and the World Health Organization's International Clinical Trials Registry and ClinicalTrials.gov for ongoing trials. Randomized controlled trials (RCTs) of propranolol for the prevention or treatment of ROP were included. The quality of the included studies was primarily assessed by the RCT tool of the Cochrane Collaboration. The included studies were quantified using a meta-analysis of relative risk (RR) estimated with a random effect model. Our original search identified 171 articles, and five studies met our criteria. A meta-analysis was performed that showed that infants orally treated with propranolol had a decreased risk of disease progression: stage progression had an RR = 0.65 [95% confidence interval (CI), 0.47-0.88]), plus disease had an RR = 0.43 [95% CI, 0.22-0.82]. The demands for additional treatments had similar protective results: laser photocoagulations had an RR = 0.55 [95% CI, 0.35-0.86]), and intravitreal injection of anti-vascular endothelial growth factor had an RR = 0.45 [95% CI, 0.22-0.90]). The oral administration of propranolol was associated with an increased risk of adverse events (RR = 2.01 [95% CI, 1.02-3.97]). High-risk adverse events included bradycardia, hypotension, not gaining enough weight, bronchospasm, hypoglycemia, apnea, and increasing ventilator need. Subgroup analysis of ROP phases and stages found that the risk in stage 2 ROP of the second phase and the individual risk factors (stage progression, RR = 0.42 [95% CI, 0.27-0.65]; plus disease, RR = 0.40 [95% CI, 0.17-0.93]; laser photocoagulation, RR = 0.31 [95% CI, 0.14-0.68]) have statistically significant differences compared with other phases and stages. Pre-term newborns with ROP, especially in stage 2 ROP of the second phase, who were orally given propranolol have a reduced risk of disease progression and demand for additional treatments, but the safety needs more attention.
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http://dx.doi.org/10.3389/fped.2021.631673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902715PMC
February 2021

The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy.

Front Physiol 2020 11;11:575722. Epub 2021 Feb 11.

Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet.

Methods: Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed.

Results: Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, and were found to be upregulated in IgAN patients, while was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio.

Conclusion: Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.
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http://dx.doi.org/10.3389/fphys.2020.575722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905042PMC
February 2021

Neuroprotection of Chikusetsu saponin V on transient focal cerebral ischemia/reperfusion and the underlying mechanism.

Phytomedicine 2021 Apr 17;84:153516. Epub 2021 Feb 17.

Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Background: Oxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate HO-induced oxidative stress in SH-SY5Y cells.

Purpose: The aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion.

Methods: Mice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry.

Results: CHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by activating AMPK and SIRT-1, respectively.

Conclusion: Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1.
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http://dx.doi.org/10.1016/j.phymed.2021.153516DOI Listing
April 2021

Recovery of early postoperative muscle strength after deep neuromuscular block by means of ultrasonography with comparison of neostigmine versus sugammadex as reversal drugs: study protocol for a randomised controlled trial.

BMJ Open 2021 02 26;11(2):e043935. Epub 2021 Feb 26.

First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Introduction: Despite the use of quantitative neuromuscular monitoring together with the administration of reversal drugs (neostigmine or sugammadex), the incidence of residual neuromuscular blockade defined as a train-of-four ratio (TOFr) <0.9 remains high. Even TOFr >0.9 cannot ensure adequate recovery of neuromuscular function when T1 height is not recovered completely. Thus, a mathematical correction of TOFr needs to be applied because the return of a normal TOFr can precede the return of a normal T1 twitch height. On the other hand, different muscles have different sensitivities to neuromuscular blockade agents; thus, complete recovery of one specific muscle group does not represent complete recovery of all other muscles. Therefore, our study aims to assess the muscle strength recovery of respiratory-related muscle groups by ultrasound and evaluate global strength using handgrip dynamometry in the early postoperative period when TOFr=0.9 and corrected TOFr (cTOFr)=0.9 with comparison of neostigmine versus sugammadex as reversal drugs.

Methods And Analysis: This study will be a prospective, single-blinded, randomised controlled trial involving 60 patients with American Society of Anesthesiologists physical status I-II and aged between 18 and 65 years, who will undergo microlaryngeal surgery. We will assess geniohyoid muscle, parasternal intercostal muscle, diaphragm, abdominal wall muscle and handgrip strength at four time points: before anaesthesia, TOFr=0.9, cTOFr=0.9 and 30 min after admission to the post anaesthesia care unit. Our primary objective will be to compare the effects of neostigmine and sugammadex on the recovery of muscle strength of different muscle groups in the early postoperative period when TOFr=0.9 and cTOFr=0.9. The secondary objective will be to observe the difference of muscle strength between the time points of TOFr=0.9 and cTOFr=0.9 to find out the clinical significance of cTOFr >0.9.

Ethics And Dissemination: The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University. The findings will be disseminated to the public through peer-reviewed scientific journals.

Trial Registration Number: ChiCTR2000033832.
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http://dx.doi.org/10.1136/bmjopen-2020-043935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919596PMC
February 2021

Modulatory Potential of LncRNA Zfas1 for Inflammation and Neuronal Apoptosis in Temporal Lobe Epilepsy.

Yonsei Med J 2021 Mar;62(3):215-223

Department of Rehabilitation Medicine, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical Univeristy, Suzhou, China.

Purpose: This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE).

Materials And Methods: Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry.

Results: Serum levels of Zfas1 were higher in TLE patients than in healthy controls (<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKβ in neurons (<0.05).

Conclusion: Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.
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http://dx.doi.org/10.3349/ymj.2021.62.3.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934098PMC
March 2021