Publications by authors named "Lin Zhang"

5,227 Publications

  • Page 1 of 1

Zonal model for predicting contaminant distribution in stratum ventilated rooms.

Indoor Air 2022 Jun;32(6):e13061

Division of Building Science and Technology, City University of Hong Kong, Hong Kong, China.

Accurate prediction of the non-uniform contaminant distribution under stratum ventilation (SV) is crucial for optimal design for reducing contaminant exposure risks. Compared with experiments and computational fluid dynamics, zonal models are convenient to implement. This study proposes a zonal model for predicting dynamic non-uniform contaminant distribution in the stratum ventilated room. The zoning method is based on the unique airflow pattern under SV, and the room is divided into the jet zone, entrainment zone, and the mixing zone. The interzonal airflow rate is derived from the profile of the supply air jet. The results show that the proposed zonal model can predict the dynamic contaminant distribution in the stratum ventilated room. Compared with the experimental measurement, the predictions show good accuracy with the mean absolute error (MAE) at 0.51-2.36 ppm and root mean squared error (RMSE) at 0.64-2.53 ppm. The error of the proposed zonal model is influenced by the degree of mixing in each subzone. The proposed zonal model shows better accuracy for non-uniform air distribution under stratum ventilation compared with the existing zonal model.
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http://dx.doi.org/10.1111/ina.13061DOI Listing
June 2022

Subthalamic nucleus deep brain stimulation programming settings do not correlate with Parkinson's disease severity.

Acta Neurochir (Wien) 2022 Jun 25. Epub 2022 Jun 25.

Department of Clinical Neurosciences, University of Calgary, 1403 29 Street NW, Calgary, AB, T2N 2T9, Canada.

Background: Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD). While the success of DBS is dependent on careful patient selection and accurate lead placement, programming parameters play a pivotal role in tailoring therapy on the individual level. Various algorithms have been developed to streamline the initial programming process, but the relationship between pre-operative patient characteristics and post-operative device settings is unclear. In this study, we investigated how PD severity correlates with DBS settings.

Methods: We conducted a retrospective review of PD patients who underwent DBS of the subthalamic nucleus at one US tertiary care center between 2014 and 2018. Pre-operative patient characteristics and post-operative programming data at various intervals were collected. Disease severity was measured using the Unified Parkinson's Disease Rating Scale score (UPDRS) as well as levodopa equivalent dose (LED). Correlation analyses were conducted looking for associations between pre-operative disease severity and post-operative programming parameters.

Results: Fifty-six patients were analyzed. There was no correlation between disease severity and any of the corresponding programming parameters. Pre-operative UPDRS scores on medication were similar to post-operative scores with DBS. Settings of amplitude, frequency, and pulse width increased significantly from 1 to 6 months post-operatively. Stimulation volume, inferred by the distance between contacts used, also increased significantly over time.

Conclusions: Interestingly, we found that patients with more advanced disease responded to electrical stimulation similarly to patients with less advanced disease. These data provide foundational knowledge of DBS programming parameters used in a single cohort of PD patients over time.
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http://dx.doi.org/10.1007/s00701-022-05279-7DOI Listing
June 2022

Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection.

Immunohorizons 2022 Jun 24;6(6):408-415. Epub 2022 Jun 24.

Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University, Indianapolis, IN; and

There are conflicting data about level and duration of Abs to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children after symptomatic or asymptomatic infection. In this human population, we enrolled adults and children in a prospective 6-mo study in the following categories: 1) symptomatic, SARS-CoV-2 PCR (SP; children, = 8; adults, = 16), 2) symptomatic, PCR, or untested (children, = 27), 3) asymptomatic exposed (children, = 13), and 4) asymptomatic, no known exposure (children, = 19). Neutralizing Abs (nAbs) and IgG Abs to SARS-CoV-2 Ags and spike protein variants were measured by multiplex serological assay. All SP children developed nAb, whereas 81% of SP adults developed nAb. Decline in the presence of nAb over 6 mo was not significant in symptomatic children (100 to 87.5%; = 0.32) in contrast to adults (81.3 to 50.0%; = 0.03). Among children with nAb ( = 22), nAb titers and change in titers over 6 mo were similar in symptomatic and asymptomatic children. In children and adults, nAb levels postinfection were 10-fold lower than those reported after SARS-CoV-2 mRNA vaccination. Levels of IgG Abs in children to SARS-CoV-2 Ags and spike protein variants were similar to those in adults. IgG levels to primary Ags decreased over time in children and adults, but levels to three spike variants decreased only in children. Children with asymptomatic or symptomatic SARS-CoV-2 infection develop nAbs that remain present longer than in adults but wane in titer over time and broad IgG Abs that also wane in level over time. However, nAb levels were lower postinfection than those reported after immunization.
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http://dx.doi.org/10.4049/immunohorizons.2200029DOI Listing
June 2022

Identification of critical genes and molecular pathways in COVID-19 myocarditis and constructing gene regulatory networks by bioinformatic analysis.

PLoS One 2022 24;17(6):e0269386. Epub 2022 Jun 24.

Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China.

Background: There is growing evidence of a strong relationship between COVID-19 and myocarditis. However, there are few bioinformatics-based analyses of critical genes and the mechanisms related to COVID-19 Myocarditis. This study aimed to identify critical genes related to COVID-19 Myocarditis by bioinformatic methods, explore the biological mechanisms and gene regulatory networks, and probe related drugs.

Methods: The gene expression data of GSE150392 and GSE167028 were obtained from the Gene Expression Omnibus (GEO), including cardiomyocytes derived from human induced pluripotent stem cells infected with SARS-CoV-2 in vitro and GSE150392 from patients with myocarditis infected with SARS-CoV-2 and the GSE167028 gene expression dataset. Differentially expressed genes (DEGs) (adjusted P-Value <0.01 and |Log2 Fold Change| ≥2) in GSE150392 were assessed by NetworkAnalyst 3.0. Meanwhile, significant modular genes in GSE167028 were identified by weighted gene correlation network analysis (WGCNA) and overlapped with DEGs to obtain common genes. Functional enrichment analyses were performed by using the "clusterProfiler" package in the R software, and protein-protein interaction (PPI) networks were constructed on the STRING website (https://cn.string-db.org/). Critical genes were identified by the CytoHubba plugin of Cytoscape by 5 algorithms. Transcription factor-gene (TF-gene) and Transcription factor-microRibonucleic acid (TF-miRNA) coregulatory networks construction were performed by NetworkAnalyst 3.0 and displayed in Cytoscape. Finally, Drug Signatures Database (DSigDB) was used to probe drugs associated with COVID-19 Myocarditis.

Results: Totally 850 DEGs (including 449 up-regulated and 401 down-regulated genes) and 159 significant genes in turquoise modules were identified from GSE150392 and GSE167028, respectively. Functional enrichment analysis indicated that common genes were mainly enriched in biological processes such as cell cycle and ubiquitin-protein hydrolysis. 6 genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) were identified as critical genes. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Etoposide, Methotrexate, Troglitazone, etc) were considered as target drugs for COVID-19 Myocarditis.

Conclusions: Through bioinformatics method analysis, this study provides a new perspective to explore the pathogenesis, gene regulatory networks and provide drug compounds as a reference for COVID-19 Myocarditis. It is worth highlighting that critical genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) may be potential biomarkers and treatment targets of COVID-19 Myocarditis for future study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269386PLOS
June 2022

Paraoxonase-1 Facilitates PRRSV Replication by Interacting with Viral Nonstructural Protein-9 and Inhibiting Type I Interferon Pathway.

Viruses 2022 May 31;14(6). Epub 2022 May 31.

State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Paraoxonase-1 (PON1), an esterase with specifically paraoxonase activity, has been proven to be involved in inflammation and infection. Porcine reproductive and respiratory syndrome virus (PRRSV) is still a major concern in pigs and causes severe economic losses to the swine industry worldwide. In this study, the role of PON1 was investigated in porcine alveolar macrophages (PAMs) during PRRSV infection. The results showed that PRRSV replication downregulated PON1, and the knockdown of PON1 significantly decreased PRRSV replication. Similarly, PON1 overexpression could enhance PRRSV replication. Interestingly, we observed that PON1 interacted with PRRSV nonstructural protein 9 (Nsp9), the RNA-dependent RNA polymerase, and the knockdown of PON1 lowered the RNA binding ability of Nsp9, suggesting that PON1 can facilitate Nsp9 function in viral replication. In addition, the knockdown of PON1 expression led to the amplification of type I interferon (IFN) genes and vice versa. In summary, our data demonstrate that PON1 facilitates PRRSV replication by interacting with Nsp9 and inhibiting the type I IFN signaling pathway. Hence, PON1 may be an additional component of the anti-PRRSV defenses.
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http://dx.doi.org/10.3390/v14061203DOI Listing
May 2022

H NMR Spectroscopy-Based Metabolomics Approach to Study the Anti-Stroke Activity of G-3702, a Novel Better Alternative to DL-3-n-Butylphthalide.

Neurochem Res 2022 Jun 23. Epub 2022 Jun 23.

Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing, 210094, People's Republic of China.

Cerebrovascular disease is the leading cause of disability and death, and ischemic stroke accounts for most stroke cases. However, few effective drugs are available for the treatment of ischemic stroke; thus, there is an urgent need to develop effective drugs to treat ischemic stroke. DL-3-n-butylphthalide (NBP) is clinically approved as an anti-ischemic drug in China, but its potential hepatotoxicity limits its use. G-3702 (a structural analogue of NBP) is synthesized with the boron hydroxyl group replacing carbonyl group. G-3702 significantly enhanced the survival of middle cerebral artery occlusion (MCAO) rats, decreased neurobehavioral deficit scores and cerebral infarct volume, comparable with NBP, which was also supported by tissue damage assessment, immunohistochemistry staining, biochemical parameters and ELISA assay. G-3702 showed better anti-stroke activity than NBP according to H NMR spectroscopy-based metabolomics analysis, demonstrating the feasibility of metabolomics approach to assess drug efficacy. G-3702 markedly ameliorated energy metabolism, attenuated oxidative and inflammatory stress during ischemia/reperfusion (I/R). G-3702 exhibited good neuroprotective effects against I/R induced injury and favorable little possibility of hepatotoxicity, which made it a promising anti-stroke drug and better NBP alternative.
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http://dx.doi.org/10.1007/s11064-022-03648-3DOI Listing
June 2022

Positivity-preserving high-order compact difference method for the Keller-Segel chemotaxis model.

Math Biosci Eng 2022 May;19(7):6764-6794

Institute of Applied Mathematics and Mechanics, Ningxia University, Yinchuan 750021, China.

The paper is concerned with development of an accurate and effective positivity-preserving high-order compact difference method for solving the Keller-Segel chemotaxis model, which is a kind of nonlinear parabolic-parabolic system in mathematical biology. Firstly, a stiffly-stable five-step fourth-order fully implicit compact difference scheme is proposed. The new scheme not only has fourth-order accuracy in the spatial direction, but also has fourth-order accuracy in the temporal direction, and the computational strategy for the nonlinear chemotaxis term is provided. Then, a positivity-preserving numerical algorithm is presented, which ensures the non-negativity of cell density at all time without accuracy loss. And a time advancement algorithm is established. Finally, the proposed method is applied to the numerical simulation for chemotaxis phenomena, and the accuracy, stability and positivity-preserving of the new scheme are validated with several numerical examples.
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http://dx.doi.org/10.3934/mbe.2022319DOI Listing
May 2022

An insight into the health beneficial of probiotics dairy products: a critical review.

Crit Rev Food Sci Nutr 2022 Jun 22:1-20. Epub 2022 Jun 22.

College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, Jiangsu, China.

Probiotic dairy products satisfy people's pursuit of health, and are widely favored because of their easy absorption, high nutritional value, and various health benefits. However, its effectiveness and safety are still controversial. This proposal aims to analyze the effect of probiotics on the quality characteristics of dairy products, clarify a series of physiological functions of probiotic dairy products and critically evaluate the effectiveness and safety of probiotic dairy products. Also, dairy products containing inactivated microorganisms were compared with probiotic products. The addition of probiotics enables dairy products to obtain unique quality characteristics, and probiotic dairy products have better health-promoting effects. This review will promote the further development of probiotic dairy products, provide directions for the research and development of probiotic-related products, and help guide the general public to choose and purchase probiotic fermentation products.
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http://dx.doi.org/10.1080/10408398.2022.2090493DOI Listing
June 2022

Comparison of CD146 +/- mesenchymal stem cells in improving premature ovarian failure.

Stem Cell Res Ther 2022 Jun 21;13(1):267. Epub 2022 Jun 21.

Laboratory of Molecular Diagnosis and Regenerative Medicine, Medical Research Center, The Affiliate Hospital of Qingdao University, Qingdao, 266000, People's Republic of China.

Background: Mesenchymal stem cells (MSCs) are a heterogeneous group of subpopulations with differentially expressed surface markers. CD146 + MSCs correlate with high therapeutic and secretory potency. However, their therapeutic efficacy and mechanisms in premature ovarian failure (POF) have not been explored.

Methods: The umbilical cord (UC)-derived CD146 +/- MSCs were sorted using magnetic beads. The proliferation of MSCs was assayed by dye670 staining and flow cytometry. A mouse POF model was established by injection of cyclophosphamide and busulfan, followed by treatment with CD146 +/- MSCs. The therapeutic effect of CD146 +/- MSCs was evaluated based on body weight, hormone levels, follicle count and reproductive ability. Differential gene expression was identified by mRNA sequencing and validated by RT-PCR. The lymphocyte percentage was detected by flow cytometry.

Results: CD146 +/- MSCs had similar morphology and surface marker expression. However, CD146 + MSCs exhibited a significantly stronger proliferation ability. Gene profiles revealed that CD146 + MSCs had a lower levels of immunoregulatory factor expression. CD146 + MSCs exhibited a stronger ability to inhibit T cell proliferation. CD146 +/- MSCs treatment markedly restored FSH and E2 hormone secretion level, reduced follicular atresia, and increased sinus follicle numbers in a mouse POF model. The recovery function of CD146 + MSCs in a reproductive assay was slightly improved than that of CD146 - MSCs. Ovary mRNA sequencing data indicated that UC-MSCs therapy improved ovarian endocrine locally, which was through PPAR and cholesterol metabolism pathways. The percentages of CD3, CD4, and CD8 lymphocytes were significantly reduced in the POF group compared to the control group. CD146 + MSCs treatment significantly reversed the changes in lymphocyte percentages. Meanwhile, CD146 - MSCs could not improve the decrease in CD4/8 ratio induced by chemotherapy.

Conclusion: UC-MSCs therapy improved premature ovarian failure significantly. CD146 +/- MSCs both had similar therapeutic effects in repairing reproductive ability. CD146 + MSCs had advantages in modulating immunology and cell proliferation characteristics.
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http://dx.doi.org/10.1186/s13287-022-02916-xDOI Listing
June 2022

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration.

J Nanobiotechnology 2022 Jun 21;20(1):291. Epub 2022 Jun 21.

Department of Histology and Embryology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.

Background: The use of keratinocytes derived from induced pluripotent stem cells (iPSCs-KCs) may represent a novel cell therapy strategy for burn treatment. There is growing evidence that extracellular vesicles, including exosomes, are primary mediators of the benefits of stem cell therapy. Herein, we thus explored the effects of exosomes produced by iPSCs-derived keratinocytes (iPSCs-KCs-Exos) in a model of deep second-degree burn wound healing and evaluated the mechanistic basis for the observed activity.

Methods: iPSCs-KCs-Exos were isolated from conditioned medium of iPSCs-KCs and verified by electron micrograph and size distribution. Next, iPSCs-KCs-Exos were injected subcutaneously around wound sites, and its efficacy was evaluated by measuring wound closure areas, histological examination, and immunohistochemistry staining. The effects of iPSCs-KCs-Exos on proliferation and migration of keratinocytes and endothelial cells in vitro were assessed by EdU staining, wound healing assays, and transwell assay. Then, high-throughput microRNA sequencing was used to explore the underlying mechanisms. We assessed the roles of miR-762 in iPSCs-KCs-Exos-induced regulation of keratinocytes and endothelial cells migration. Furthermore, the target gene which mediated the biological effects of miR-762 in keratinocytes and endothelial cells was also been detected.

Results: The analysis revealed that iPSCs-KCs-Exos application to the burn wound drove the acceleration of wound closure, with more robust angiogenesis and re-epithelialization being evident. Such iPSCs-KCs-Exos treatment effectively enhanced endothelial cell and keratinocyte migration in vitro. Moreover, the enrichment of miR-762 was detected in iPSCs-KCs-Exos and was found to target promyelocytic leukemia (PML) as a means of regulating cell migration through a mechanism tie to integrin beta1 (ITGB1).

Conclusion: These results thus provide a foundation for the further study of iPSCs-KCs-Exos as novel cell-free treatments for deep second-degree burns.
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http://dx.doi.org/10.1186/s12951-022-01504-8DOI Listing
June 2022

CPT2 K79 Acetylation Regulates Platelet Lifespan.

Blood Adv 2022 Jun 21. Epub 2022 Jun 21.

Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Short lifespan of platelets is a major challenge to platelet transfusion services due to the lack of effective intervention. Here, we found that the accumulation of long-chain acylcarnitines (LCACs) is responsible for mitochondrial damage and platelet storage lesion. Further studies showed that the blockade of fatty acid oxidation and the activation of AMPK/ACC/CPT1 pathways that promote fatty acid metabolism are important reasons for the accumulation of LCACs. The excessive accumulation of LCACs can cause mitochondrial damage and short lifespan of stored platelets. The mechanism study elucidated that NAD+ exhaustion and the subsequent decrease in Sirt3 activity caused an increase in the level of CPT2 K79 acetylation, which is the primary cause of the blockade of fatty acid oxidation and the accumulation of LCACs. Blocking LCACs generation with the inhibitors of AMPK or CPT1, the agonists of Sirt3, and antioxidants tremendously retarded platelet storage lesion in vitro and prolong the survival of stored platelets in vivo post transfusion by single or combined use. In short, we discovered that CPT2 acetylation attenuates fatty acid oxidation and exacerbates platelet storage lesion and may serve as a new target for improving platelet storage quality.
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http://dx.doi.org/10.1182/bloodadvances.2021006687DOI Listing
June 2022

PDZK1 interacting protein 1 (PDZK1IP1) promotes the progression of papillary thyroid cancer.

J Clin Endocrinol Metab 2022 Jun 21. Epub 2022 Jun 21.

Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province 430030, China.

Background: The incidence of papillary thyroid cancer (PTC) has increased rapidly in recent decades, and tumor progression events are common in PTC. The purpose of our study is to identify the differentially expressed genes (DEGs) correlated with PTC progression and investigate the function of PDZK1IP1 in PTC.

Methods: We first analyzed DEGs associated with PTC progression between paired PTC and normal thyroid tissues in three GEO datasets (GSE29265, GSE33630 and GSE60542) and TCGA database. Data from TCGA database and our institution were utilized to explore the relationship between PDZK1IP1 expression and clinicopathological characteristics of PTC. The CCK8 cell proliferation assay, clone formation assay, flow cytometry assay and the xenograft model were used to investigate the function of PDZK1IP1 in PTC.

Results: 39 DEGs associated with PTC progression were identified, in which only PDZK1IP1 was upregulated in PTC tissue at both mRNA and protein levels. Besides, we found that high expression of PDZK1IP1 in TCGA database was associated with poor progression-free survival, extrathyroidal extension, high stage, tall cell variant and BRAF V600E mutation of the PTC (P<0.001). In our collected samples, high expression of PDZK1IP1 was only related to lymph node metastasis (P<0.05). Overexpression of PDZK1IP1 significantly promoted proliferation and inhibited apoptosis of PTC cells. Knockdown of PDZK1IP1 significantly inhibited proliferation, promoted apoptosis, and prevented xenograft formation of PTC cells.

Conclusion: PDZK1IP1 is an oncogene for tumorigenesis and development of PTC and might be a potential therapeutic target.
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http://dx.doi.org/10.1210/clinem/dgac376DOI Listing
June 2022

Fifteen-year mortality and prognostic factors in patients with dilated cardiomyopathy: persistent standardized application of drug therapy and strengthened management may bring about encouraging change in an aging society.

J Geriatr Cardiol 2022 May;19(5):335-342

Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated cardiomyopathy (DCM). The study aimed to investigate the all-cause mortality up to 15 years (mean 7.9 ± 5.7 years) in such patients, and the independent prognostic factors influencing their long-term mortality.

Methods: One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003. The mean age of patients was 59.5 ± 10.4 years, and approximately 57% were male. They were followed up by telephone or outpatient visit at least every three months until 2019 or all-cause death occurred. Predictors of mortality were identified using multivariate logistic regression analysis.

Results: During the 15 years of follow-up, five patients were lost to follow-up, and the complete data records of 161 patients were included in the analysis. Patients were treated with angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin-receptor blocker (ARB), β-blockers, mineralocorticoid receptor antagonist (MRA), diuretics and digitalis from 2002 to 2004, and maintained at the maximum tolerated doses between 2004 and 2019. Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg, respectively. All-cause mortality in the first five years was 55.9%. The independent risk factors for the 5-year mortality were age ≥ 70 years old (OR = 5.45, 0.006), systolic blood pressure (SBP) > 120 mmHg (OR = 3.63, 0.004), 6-minute walk distance (6MWD) < 450 m (OR = 3.84, 0.001). 15-year all-cause mortality was 65.8%. The independent risk factors for 15-year mortality were age ≥ 70 years old (OR = 16.07, 0.009), LVEF ≤ 35% (OR = 5.69, 0.003), and SBP > 120 mmHg (OR = 9.56, < 0.001).

Conclusions: This study was the first to demonstrate the 15-year survival rate of 34% in DCM patients. The DCM patients' first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management. The mortality then plateaued in the following 10 years. Age ≥ 70 years, LVEF ≤ 35%, and SBP > 120 mmHg were independent predictors of 15-year all-cause mortality.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2022.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170907PMC
May 2022

Circular RNA FUNDC1 for Prediction of Acute Phase Outcome and Long-Term Survival of Acute Ischemic Stroke.

Front Neurol 2022 3;13:846198. Epub 2022 Jun 3.

Department of Neurology, Key Laboratory of Developmental Genes and Human Disease, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China.

Circular RNAs (CircRNAs) have shown promising potential in the diagnosis and the prediction of outcomes of stroke. This study aimed to explore the potential value of circRNAs for identifying acute neurological deterioration and estimating long-term survival for acute ischemic stroke (AIS). One hundred healthy controls and 200 patients with AIS within 72 h were recruited, 140 of whom were admitted within 24 h after onset. CircRNA levels in peripheral blood were measured by quantitative polymerase chain reaction (qPCR). Compared to the controls, the levels of three circRNAs were significantly increased in three subgroups of patients, including large artery atherosclerosis (LAA) stroke, small artery occlusion (SAO) stroke, and cardioembolism (CE) stroke (all < 0.001). Among, LAA stroke patients had higher levels of circular RNA FUNDC1 (circFUNDC1) compared to SAO stroke patients ( = 0.015). CircFUNDC1 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on the 7th day only in LAA patients ( = 0.048, = 0.226). It should be noted that the levels of circFUNDC1 in patients with early neurological deterioration (END), admitted within 24 h after onset, were significantly higher than those without END ( = 0.013). In addition, circFUNDC1 levels positively correlated with baseline NIHSS scores ( = 0.016, = 0.203) or the 7th day NIHSS scores ( = 0.001, = 0.289) in patients within 24 h after onset. Importantly, after 18 months of follow-up, a significant difference was observed on survival Kaplan-Meier curves ( = 0.042) between AIS patients with low (below cut-off) or high circFUNDC1 levels (above cut-off). Circulating circFUNDC1 could be a potential biomarker for predicting acute-phase outcome and long-term survival in AIS.
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http://dx.doi.org/10.3389/fneur.2022.846198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203888PMC
June 2022

A combined approach to evaluate total phosphorus/inorganic phosphate levels in plants.

STAR Protoc 2022 Sep 14;3(3):101456. Epub 2022 Jun 14.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology & Ecology, Chinese Academy of Sciences, Shanghai, China.

Inorganic phosphate (Pi) and phosphorus (P) homeostasis are essential for plant growth and yield, and reliable detection of dynamic Pi/P in different tissues is important for studying their biological functions. Here, we report a combined protocol for rapid determination of Pi/P levels. We first perform P NMR assay to reveal the intracellular Pi distribution and then dissect the level of Pi/P by the chromogenic reaction and ICP-MS analysis. Finally, we take μXRF element fluorescence assay to achieve the visual P distribution. For complete details on the use and execution of this protocol, please refer to Ma et al. (2021).
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http://dx.doi.org/10.1016/j.xpro.2022.101456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204740PMC
September 2022

miR-107 attenuates sepsis-induced myocardial injury by targeting PTEN and activating the PI3K/AKT signaling pathway.

Cells Tissues Organs 2022 Jun 17. Epub 2022 Jun 17.

Sepsis is a public health problem worldwide. This study investigated the mechanism of miR-107 on sepsis-induced myocardial injury. Sepsis rat models were established by cecal ligation and puncture, and the cell model was established using lipopolysaccharide (LPS)-induced cardiomyocytes. Cardiac function indexes of rats were measured using echocardiography. Pathological changes in the rat myocardium were observed using histological staining. Expressions of miR-107 in the serum of rats and cardiomyocyte were detected after the treatment of miR-107 mimic or/and pcDNA3.1-PTEN, followed by assessment of cell cycle, proliferation, and apoptosis. Binding sites of miR-107 and PTEN were predicted. PTEN, PI3K, p-PI3K, AKT, and p-AKT expressions in LPS-induced cardiomyocytes were measured. miR-107 was significantly downregulated in the serum of CLP rats and LPS-induced cardiomyocytes. miR-107 overexpression remarkably improved cardiac function and histological changes, decreased inflammatory factors, and alleviated the sepsis-induced myocardial injury in rats. In LPS-induced cardiomyocytes, miR-107 overexpression increased cardiomyocyte proliferation, inhibited apoptosis, and enhanced the proportion of cardiomyocytes arrested in S and G2/M phases. miR-107 targeted PTEN. PTEN overexpression partially reversed the inhibition of miR-107 mimic on cardiomyocyte apoptosis. miR-107 overexpression activated the PI3K/AKT pathway by inhibiting PTEN. To conclude, miR-107 activates the PI3K/AKT pathway by inhibiting PTEN, thus attenuating sepsis-induced myocardial injury and LPS-induced cardiomyocyte apoptosis.
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http://dx.doi.org/10.1159/000525476DOI Listing
June 2022

Mechanisms of Pb(II) coprecipitation with natrojarosite and its behavior during acid dissolution.

J Environ Sci (China) 2022 Dec 1;122:128-137. Epub 2022 Feb 1.

Institute of Environmental Engineering, School of Metallurgy and Environment, Central South University, Changsha 410083, China; Chinese National Engineering Research Center for Control & Treatment of Heavy Metal Pollution, Changsha 410083, China.

Lead (Pb) coprecipitation with jarosite is common in natural and engineered environments, such as acid mine drainage (AMD) sites and hydrometallurgical industry. Despite the high relevance for environmental impact, few studies have examined the exact interaction of Pb with jarosite and the dissolution behavior of each phase. In the present work, we demonstrate that Pb mainly interacts with jarosite in four modes, namely incorporation, occlusion, physically mixing, and chemically mixing. For comparison, the four modes of Pb-bearing natrojarosite were synthesized and characterized separately. Batch dissolution experiments were undertaken on these synthetic Pb-bearing natrojarosites under pH 2 to simulate the AMD environments. The introduction of Pb decreases the final Fe releasing efficiency of jarosite-type compounds from 18.18% to 3.45%-5.01%, showing a remarkable inhibition of their dissolution. For Pb releasing behavior, PbSO dissolves in preference to Pb-substituted natrojarosite, i.e., (Na, Pb)-jarosite, which primarily results in the sharp increase of Pb releasing concentration (> 40 mg/L). PbSO occlusion by jarosite-type compounds can significantly reduce the release of Pb. The results of this study could provide useful information regarding Fe and Pb cycling in acidic natural and engineered environments.
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http://dx.doi.org/10.1016/j.jes.2021.10.006DOI Listing
December 2022

Toxicity of Nanoparticles of AgO, La₂O₃, CuO, AgO-Fe₃O₄, Ag-Graphene, and GO-Cu-AgO to the Fungus Y12 Isolated from Degraded Biodiesel and the Bacterium .

J Biomed Nanotechnol 2022 Mar;18(3):928-938

College of Agriculture and Biology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, 510225, China.

Y12 ( Y12), a fungal isolated from biodiesel caused serious biodiesel contamination and resulting in biofouling and corrosion, especially during storage. Nanoparticles (NPs) composed of silver, copper, iron, and graphene or their binary mixtures were examined as environmental inhibitors against the fungus Y12, a biodiesel contaminant. Exposure of Y12 and () to low concentrations of Ag-based nanoparticles (from 0.01 to 0.05 mg mL) resulted in excellent growth inhibition. The half-maximal inhibitory concentration (IC) of Y12 by La₂O₃ NPs was 138 times greater when compared with silver (AgO). The median effective concentration (EC) of La₂O₃ NPs on was 379 times more than Y12. At this same concentration, was uninhibited after exposure to the NPs. However, a fluorescein diacetate analysis showed the Ag-based NPs (including AgO, AgO-Fe₃O₄ and GO-Cu-AgO) significantly reduced the metabolic activity for both of the compared organisms. Compared with other metal oxide NPs, AgO and AgO-Fe₃O₄ NPs display strong bactericidal effect with higher stability and dispersibility, with the zeta potential of -22.27 mV and poly-dispersity index (PDI) values of 0.36. These results demonstrate the broad-spectrum biological inhibition that occurs with both Ag-based bimetallic and graphene oxide nanoparticles and the combined utilization of Ag-based NPs paves a new way for inhibits the biodegradation of biodiesel.
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http://dx.doi.org/10.1166/jbn.2022.3299DOI Listing
March 2022

Acute stress deteriorates breast meat quality of Ross 308 broiler chickens by inducing redox imbalance and mitochondrial dysfunction.

J Anim Sci 2022 Jun 17. Epub 2022 Jun 17.

College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.

This study investigated the effects of acute stress on breast meat quality, redox status and mitochondrial function in pectoralis major (PM) muscle of broilers. A total of 168 broiler chickens (42-day-old, Ross 308) were randomly divided into control (CON) and pre-slaughter transport (T) treatments. A broiler was an experimental unit. Each treatment consisted of 84 broilers, and they were put in 12 crates with 7 broilers each. Broilers in the T group were transported according to a designed protocol, and the CON broilers were kept in crates under normal living conditions before slaughtering. Based on the meat quality traits assessed at postmortem 24 h, all PM muscles of the transported broilers were further classified into normal (T-NOR) and pale, soft and exudative (PSE)-like (T-PSE) groups for the determination of redox status in PM muscle and isolated mitochondria, energy metabolites, mitochondrial electron transport chain complexes activities, as well as mitochondrial function-modulating genes expression. Compared with CON, the extent of lipid peroxidation as well as protein oxidation were significantly increased in both PM muscles and mitochondria in T-PSE (P < 0.05), whereas not in T-NOR. Higher activities of glutathione peroxidase, total superoxide dismutase and Cu-Zn superoxide dismutase were observed in PM muscle of T-NOR broilers as compared with CON (P < 0.05). Pre-slaughter transport increased the generation of reactive oxygen species, as well as enhanced antioxidant capacity in PM mitochondria of broilers (P < 0.05). Compared with CON, the ATP content, activities of complex I and III, as well as relative mitochondrial membrane potential and swelling were significantly decreased in T-PSE (P < 0.05), whereas no significant changes in either ATP content or complex I activity were observed in T-NOR. Pre-slaughter transport enhanced the mRNA expression of regulators involved in the glutathione system, thioredoxin 2 system and mitochondrial biosynthesis in PM muscle of broilers (P < 0.05). Moreover, we noticed a more evident enhancement effect in T-NOR than in T-PSE (P < 0.05). Overall, this work indicates that acute stress-induced redox imbalance and mitochondrial dysfunction have significant implications for the development of PSE-like meat.
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http://dx.doi.org/10.1093/jas/skac221DOI Listing
June 2022

Care engagement with healthcare providers and symptom management self-efficacy in women living with HIV in China: secondary analysis of an intervention study.

BMC Public Health 2022 Jun 15;22(1):1195. Epub 2022 Jun 15.

Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.

Background: Symptom management self-efficacy is a prerequisite for individuals to fully manage their symptoms. The literature reports associations between engagement with healthcare providers (HCPs), internalized stigma, and types of self-efficacy other than symptom management. However, the factors of symptom management self-efficacy are not well understood. This study aimed to investigate the relationship among engagement with HCPs, internalized stigma, and HIV symptom management self-efficacy in Chinese women living with HIV (WLWH).

Methods: This current analysis was part of the original randomized control trial, we used data collected from 41 women living with HIV (WLWH) assigned to an intervention arm or a control arm from Shanghai and Beijing, China, at baseline, Week 4 and Week 12. The CONSORT checklist was used. The study was registered in the Clinical Trial Registry (#NCT03049332) on 10/02/2017.

Results: The results demonstrate that HCPs should increase engagement with WLWH when providing care, thereby improving their symptom management self-efficacy. The results suggested that participants' engagement with HCPs was significantly positively correlated with their HIV symptom management self-efficacy in the latter two time points. Internalized stigma was significantly negatively correlated with HIV symptom management self-efficacy only at the 4-week follow-up.

Conclusions: This study demonstrated the positive effect of engagement with HCPs on WLWHs' symptom management self-efficacy as well as the negative effect of internalized stigma on symptom management self-efficacy. Future research can further test the relationship between the three key concepts, as well as explore interventions to decrease internalized stigma.
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http://dx.doi.org/10.1186/s12889-022-13573-3DOI Listing
June 2022

Identification of useful genes from multiple microarrays for ulcerative colitis diagnosis based on machine learning methods.

Sci Rep 2022 Jun 15;12(1):9962. Epub 2022 Jun 15.

Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, Chinese EQUATOR Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with an increasing incidence and prevalence worldwide. The diagnosis for UC mainly relies on clinical symptoms and laboratory examinations. As some previous studies have revealed that there is an association between gene expression signature and disease severity, we thereby aim to assess whether genes can help to diagnose UC and predict its correlation with immune regulation. A total of ten eligible microarrays (including 387 UC patients and 139 healthy subjects) were included in this study, specifically with six microarrays (GSE48634, GSE6731, GSE114527, GSE13367, GSE36807, and GSE3629) in the training group and four microarrays (GSE53306, GSE87473, GSE74265, and GSE96665) in the testing group. After the data processing, we found 87 differently expressed genes. Furthermore, a total of six machine learning methods, including support vector machine, least absolute shrinkage and selection operator, random forest, gradient boosting machine, principal component analysis, and neural network were adopted to identify potentially useful genes. The synthetic minority oversampling (SMOTE) was used to adjust the imbalanced sample size for two groups (if any). Consequently, six genes were selected for model establishment. According to the receiver operating characteristic, two genes of OLFM4 and C4BPB were finally identified. The average values of area under curve for these two genes are higher than 0.8, either in the original datasets or SMOTE-adjusted datasets. Besides, these two genes also significantly correlated to six immune cells, namely Macrophages M1, Macrophages M2, Mast cells activated, Mast cells resting, Monocytes, and NK cells activated (P  <  0.05). OLFM4 and C4BPB may be conducive to identifying patients with UC. Further verification studies could be conducted.
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http://dx.doi.org/10.1038/s41598-022-14048-6DOI Listing
June 2022

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands.

RSC Adv 2022 May 18;12(23):14912-14916. Epub 2022 May 18.

State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmaceutical Sciences, Guizhou Medical University 550004 Guiyang China

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.
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http://dx.doi.org/10.1039/d2ra02211gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115770PMC
May 2022

A 4-year-old boy with a ventricular mass.

Brain Pathol 2022 Jun 14:e13081. Epub 2022 Jun 14.

Department of Pathology, Kunming Children's Hospital, Kunming, P.R. China.

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http://dx.doi.org/10.1111/bpa.13081DOI Listing
June 2022

Activin B-activated Cdc42 signaling plays a key role in regulating adipose-derived mesenchymal stem cells-mediated skin wound healing.

Stem Cell Res Ther 2022 Jun 11;13(1):248. Epub 2022 Jun 11.

Department of Histology and Embryology, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Key Laboratory of Construction and Detection in Tissue Engineering of Guangdong Province, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Background: In our previous study, activin B in combination with ADSCs enhances skin wound healing. However, the underlying molecular mechanisms are not well studied. Cdc42 is recognized to play a critical role in the regulation of stem cells.

Methods: Pull-down assay was performed to investigate the activity of Cdc42. The dominant-negative mutant of Cdc42 (Cdc42N17) was used to explore the role of Cdc42 in activin B-induced ADSCs migration, proliferation, and secretion in vitro. Cdc42N17-transfected ADSCs were injected into a full-thickness excisional wound model to explore their efficiency in wound healing in vivo. The wound healing efficacy was evaluated by the wound closure rates and histological examination. The neovascularization and wound contraction were detected by immunohistochemistry staining of CD31 and α-SMA. Finally, the underlying mechanisms were explored by RNA sequencing.

Results: Cdc42N17 inhibited ADSCs migration, proliferation, and secretion induced by activin B. Furthermore, Cdc42N17-transfected ADSCs inhibited the wound closure rate and suppressed the expression of CD31 and α-SMA induced by activin B in vivo. The RNA sequencing showed that the differentially expressed genes in Cdc42N17-transfected ADSCs versus ADSCs were associated with cell migration, proliferation, and adhesion. Further study revealed that the Cdc42-Erk-Srf pathway was required for activin B-induced proliferation in ADSCs.

Conclusions: Our study indicates that Cdc42 plays a crucial role in ADSCs-mediated skin wound healing induced by activin B.
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http://dx.doi.org/10.1186/s13287-022-02918-9DOI Listing
June 2022

Cucurbitacin B alleviates cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome-mediated inflammation and reducing oxidative stress.

Biosci Biotechnol Biochem 2022 Jun 11. Epub 2022 Jun 11.

Department of Neurology, First Affiliated Hospital, Soochow University, 899 Pinghai street, Suzhou, China.

Cucurbitacin B (CuB) has been demonstrated to possess anti-inflammatory and antioxidative properties. However, the effect of CuB on cerebral ischemia/reperfusion (I/R) injury was unclear. In this work, we found that CuB significantly elevated cell viability, decreased lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, and proinflammatory factor levels in oxygen-glucose deprivation/reoxygenation-exposed PC12 cells, reduced cerebral infarction volume and neuronal apoptosis, inhibited oxidative stress and inflammation, and improved neurological function in mice with middle cerebral artery occlusion-induced cerebral I/R injury. Meanwhile, CuB decreased levels of NLRP3, cleaved caspase-1, and cleaved interleukin-1β, which were upregulated by I/R injury. Moreover, upregulation of NLRP3 dramatically reversed the effects of CuB on NLRP3 inflammasome activation, cell viability, and levels of proinflammatory factors in vitro. In conclusion, this study demonstrated that CuB attenuated cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation and reducing oxidative stress.
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http://dx.doi.org/10.1093/bbb/zbac065DOI Listing
June 2022

Clinical Features, Management and Maternal-Infant Prognosis in Patients with Complete Uterine Rupture in the Second and Third Trimester of Pregnancy.

Altern Ther Health Med 2022 Jun 10. Epub 2022 Jun 10.

Objectives: Our study aimed to investigate the clinical features, management, and maternal-infant prognosis in patients with complete uterine rupture in the second and third trimester of pregnancy.

Methods: A total of 15 patients with complete uterine rupture in their second and third trimester of pregnancy who were admitted to our hospital between January 2012 and December 2020 were included in our study. The patients enrolled were divided into the scar group (11 patients) and the non-scar group (4 patients) according to the existence or absence of a uterine scar. The general data, clinical characteristics and follow-up results in the 2 groups were compared.

Results: There was no significant difference in age, pregnancy duration or delivery cycle between the 2 groups (P > .05). The incidence of original scar rupture in the scar group was significantly higher than in the non-scar group (P > .05). No significant difference was found in clinical characteristics between the scar and the non-scar groups (P > .05). The most common clinical features included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. A total of 3 patients were misdiagnosed as having surgical disease. After completing relevant examinations, the uterine rupture was repaired surgically; the patients were discharged after blood transfusion, and their condition resolved. In all, 3 patients in the non-scar group and 1 patient in the scar group were transferred to the intensive care unit (ICU). All 15 patients were discharged after treatment. Follow-up was completed by all patients for 12 to 36 months, with an average follow-up time of 23.09 ± 2.19 months. Of the 15 patients, 2 underwent induced abortion after 24 months due to unplanned pregnancy. A 5-minute Apgar score of ≤7 in the scar group was higher than that in the non-scar group, but the difference was not statistically significant (P > .05). Perinatal mortality in the 15 patients was 40.00% (6/15).

Conclusion: The most common clinical features in patients with complete uterine rupture in the second and third trimester of pregnancy included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. In addition, a remarkably worse maternal-infant prognosis was seen in patients with complete uterine rupture in the second and third trimester of scarless pregnancy compared with patients with complete uterine rupture in the second and third trimester of scarred pregnancy.
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June 2022

Structural Characterization and In-Vitro Antioxidant and Immunomodulatory Activities of Polysaccharide Fractions Isolated from L.

Molecules 2022 Jun 6;27(11). Epub 2022 Jun 6.

Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia.

L. is an important anticancer herb used in traditional Chinese medicine. The molecular basis underpinning the anticancer activity is complex and not fully understood, but the herbal polysaccharides, broadly recognised as having immunomodulatory, antioxidant and anticancer activities, are potential key active agents. To examine the functions of polysaccharides from A. annua, their immunomodulatory and antioxidant potentials were evaluated, as well as their structural characterization. The water-soluble polysaccharides (AAPs) were fractionated using size-exclusion chromatography to obtain three dominant fractions, AAP-1, AAP-2 and AAP-3, having molecular masses centered around 1684, 455 and 5.8kDa, respectively. The antioxidant potentials of the isolated polysaccharides were evaluated by measuring radical scavenging activities against DPPH (2,2-diphenyl-1-picrylhydrazyl radical), ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid radical ion), and the OH (hydroxyl radical). AAP-1 displayed high antioxidant activities against these radicals, which were 68%, 73% and 78%, respectively. AAP-2 displayed lower scavenging activities than the other two fractions. Immunostimulatory activities of AAPs were measured using mouse macrophages. The three polysaccharide fractions displayed significant antioxidant activities and stimulated the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). AAP-1 showed significant immunostimulatory activity (16-fold increase in the production of IL-6 compared to the control and 13-fold increase in the production of TNF-α) with low toxicity (>60% cell viability at 125 μg/mL concentration). Preliminary structural characterization of the AAPs was carried out using gas chromatography (GC) and FTIR techniques. The results indicate that AAP-1 and AAP-2 are pyranose-containing polysaccharides with β-linkages, and AAP-3 is a β-fructofuranoside. The results suggest that these polysaccharides are potential candidates for immunotherapy and cancer treatment.
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http://dx.doi.org/10.3390/molecules27113643DOI Listing
June 2022

The anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, minimally impacts the endogenous immune response to COVID-19 vaccination.

Sci Transl Med 2022 Jun 9:eabn3041. Epub 2022 Jun 9.

Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20850, USA.

As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from a population of nursing home residents and staff enrolled in a clinical trial who were randomized to either bamlanivimab treatment or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines. This post-hoc analysis assessed the immune response to vaccination for 135 participants without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not efficiently bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo recipients mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category, and vaccine type with any observed differences of uncertain clinical importance. These findings are pertinent for informing public health policy with results that suggest that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 monoclonal antibody infusion.
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http://dx.doi.org/10.1126/scitranslmed.abn3041DOI Listing
June 2022

The Antithrombotic Effect of Recombinant Neorudin on Thrombi.

Drug Des Devel Ther 2022 2;16:1667-1678. Epub 2022 Jun 2.

Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.

Introduction: Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials.

Methods: The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction.

Results: In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding side effects were significantly attenuated. Moreover, when the antithrombotic effects were similar, EH had a shorter bleeding time and was associated with less bleeding than low molecular weight heparin (LMWH). EH had a therapeutic effect on thrombotic cerebral infarction without increasing the occurrence of cerebral hemorrhage.

Conclusion: The findings from the preclinical animal models used in this study showed that EH could not only effectively inhibit thrombus formation but also reduce the risk of bleeding.
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http://dx.doi.org/10.2147/DDDT.S353088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169676PMC
June 2022

Discovery of Novel Tetrahydro-β-carboline Containing Aminopeptidase N Inhibitors as Cancer Chemosensitizers.

Front Oncol 2022 23;12:894842. Epub 2022 May 23.

Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, China.

Aminopeptidase N (APN, CD13) is closely associated with the development and progression of cancer. Previous studies suggested APN as a biomarker for cancer stem cells. APN inhibitors have been intensively evaluated as chemosensitizers for cancer treatments. In the present study, tetrahydro--carboline scaffold was introduced to the structure of APN inhibitors. The synthesized compounds showed potent enzyme inhibitory activities compared with Bestatin, an approved APN inhibitor, in cell-based enzymatic assay. In combination with chemotherapeutic drugs, representative APN inhibitor molecules , and significantly improved the antiproliferative potency of anticancer drugs in the tests. Further mechanistic studies revealed that the anticancer effects of these drug combinations are correlated with decreased APN expression, increased ROS level, and induction of cell apoptosis. The spheroid-formation assay and colony-formation assay results showed effectiveness of Paclitaxel-APN inhibitor combination against breast cancer stem cell growth. The combined drug treatment led to reduced mRNA expression of OCT-4, SOX-2 and Nanog in the cancer stem cells tested, suggesting the reduced stemness of the cells. In the study, the selected APN inhibitors, especially , exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies.
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http://dx.doi.org/10.3389/fonc.2022.894842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168271PMC
May 2022
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