Publications by authors named "Jia He"

577 Publications

The role of hypertension on the severity of COVID-19: a review.

J Cardiovasc Pharmacol 2021 Jul 22. Epub 2021 Jul 22.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China Institute of Hospital Pharmacy, Central South University, Changsha 410008, China.

Abstract: The novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a global pandemic. The substantial morbidity and mortality associated with the infection has prompted us to understand potential risk factors that can predict patient outcomes. Hypertension has been identified as the most prevalent cardiovascular comorbidity in COVID-19 patients, that demonstrably increases the risk of hospitalization and death. Initial studies implied that renin-angiotensin-aldosterone system (RAAS) inhibitors might increase the risk of viral infection and aggravate disease severity, thereby causing panic given the high global prevalence of hypertension. Nonetheless, subsequent evidence supported the administration of antihypertensive drugs, and noted that they do not increase the severity of COVID-19 infection in patients with hypertension; rather, may have a beneficial effect. To date, the precise mechanism by which hypertension predisposes to unfavorable outcomes in patients with COVID-19 remains unknown. In this mini-review, we elaborate on the pathology of SARS-CoV-2 infection coexisting with hypertension, and summarize potential mechanisms, focusing on the dual roles of angiotensin converting enzyme 2 (ACE2) and the disorders of RAAS in COVID-19 and hypertension. The effects of proinflammatory factors released due to immune response, and gastrointestinal dysfunction in COVID-19 are also discussed.
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http://dx.doi.org/10.1097/FJC.0000000000001116DOI Listing
July 2021

Application of Right Bronchial Occlusion under Artificial Pneumothorax in the Thoracic Phase of Minimally Invasive McKeown Esophagectomy.

Ann Thorac Cardiovasc Surg 2021 Jul 28. Epub 2021 Jul 28.

Department of Thoracic Surgery, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, China.

Purpose: To evaluate the feasibility and safety of single-lumen endotracheal intubation combined with right bronchial occlusion (SLET) under artificial pneumothorax in minimally invasive McKeown esophagectomy.

Methods: A total of 165 patients who underwent minimally invasive McKeown esophagectomy at Peking Union Medical College Hospital were retrospectively analyzed. In all, 48 patients received double-lumen endotracheal intubation (DLET group), and 117 patients received SLET-B (SLET-B group). Clinical data, intraoperative hemodynamics, surgical variables, and postoperative complications were analyzed and compared.

Results: Compared with the DLET group, a shorter intubation time and lower tube dislocation rate were found in the SLET-B group. In the thoracic phase, with the application of artificial pneumothorax, patients in the SLET-B group had lower partial pressure of carbon dioxide (PaCO) and end-tidal carbon dioxide pressure (PetCO) values and higher pH than those in the DLET group. Patients in the SLET-B group had shorter thoracic phase times and hospital stays and less intraoperative hemorrhage than those in the DLET group. The numbers of thoracic and bilateral recurrent laryngeal lymph nodes harvested were significantly higher in the SLET-B group.

Conclusion: SLET under artificial pneumothorax is feasible and safe in minimally invasive McKeown esophagectomy.
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http://dx.doi.org/10.5761/atcs.oa.21-00055DOI Listing
July 2021

Construction of a magnetic covalent organic framework with synergistic affinity strategy for enhanced glycopeptide enrichment.

J Mater Chem B 2021 Jul 23. Epub 2021 Jul 23.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China.

Considering the inherent properties of glycopeptides, such as glycan structure, size, and hydrophilicity, affinity materials possessing suitable functional molecule-glycan interactions, matched channels with size exclusion, and surfaces with hydrophilic interactions are preferred for glycopeptide separation in biological samples. Here, a novel boronic-acid-functionalized magnetic covalent organic framework was prepared through epitaxial growth and multi-ligand strategies. The multi-ligand strategy was firstly employed to prepare functionalized magnetic covalent organic framework without any post-functionalization protocol. Notably, the proposed strategy was found to be time saving, robust, and reproducible. The versatile magnetic covalent organic framework nanocomposite was endowed with phenylboronic acid functional molecules, strong hydrophilic features, mesoporous channels, fast magnetic responsiveness, and a large surface area. Benefitting from multiple affinity interactions, namely, synergistic reversible covalent interactions and hydrophilic affinity interactions, the nanocomposite presented extremely high performance in the recognition of intact N-glycopeptides. The inherent properties endowed the nanocomposite with excellent enrichment performance for N-glycopeptides: excellent selectivity (1 : 2000, IgG/BSA, m/m), an ultralow detection limit (0.05 fmol μL-1), and a good size-exclusion effect (1 : 500, IgG digests/BSA, m/m). More excitingly, a total of 1921 unique intact glycopeptides assigned to 1154 glycoproteins were identified from rat liver tissue; this performance is superior to that of commercial products. Additionally, the nanocomposite was successfully applied to enrich intact glycopeptides of exosomes extracted from healthy individuals and renal failure patients, providing a novel concept for the design of materials using a synergistic affinity strategy for sample preparation in glycoproteomics.
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http://dx.doi.org/10.1039/d1tb01168eDOI Listing
July 2021

Fluid shear stress activates YAP to promote epithelial-mesenchymal transition in hepatocellular carcinoma.

Mol Oncol 2021 Jul 14. Epub 2021 Jul 14.

Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

Epithelial-mesenchymal transition (EMT) mediated by fluid shear stress (FSS) in the tumor microenvironment plays an important role in driving metastasis of the malignant tumor. As a mechanotransducer, Yes-associated protein (YAP) is known to translocate into the nucleus to initiate transcription of genes involved in cell proliferation upon extracellular biophysical stimuli. Here, we showed that FSS facilitated cytoskeleton rearrangement in hepatocellular carcinoma cells, which led to the release of YAP from its binding partner, integrin β subunit, in the cytomembrane. Moreover, we found that upregulation of guanine nucleotide exchange factor (GEF)-H1, a microtubule-associated Rho GEF, is a critical step in the FSS-induced translocation of YAP. Nuclear YAP activated the expression of the EMT-regulating transcription factor SNAI1, but suppressed the expression of N6-methyladenosine (m A) modulators; together, this promoted the expression of EMT-related genes. We also observed that FSS-treated HepG2 cells showed markedly increased tumorigenesis and metastasis in vivo. Collectively, our findings unravel the underlying molecular processes by which FSS induces translocation of YAP from the cytomembrane to the nucleus, contributes to EMT and enhances metastasis in hepatocellular carcinoma.
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http://dx.doi.org/10.1002/1878-0261.13061DOI Listing
July 2021

Atrial fibrillation in critically ill patients who received prolonged mechanical ventilation: a nationwide inpatient report.

Korean J Intern Med 2021 Jul 12. Epub 2021 Jul 12.

Department of Health Statistics, Second Military Medical University, Shanghai, China.

Background/aims: To evaluate temporal trends of atrial fibrillation (AF) prevalence in critically ill patients who received prolonged mechanical ventilation (MV) in the United States.

Methods: We used the 2008 to 2014 National Inpatient Sample to compute the weighted prevalence of AF among hospitalized adult patients on prolonged MV. We used multivariable-adjusted models to evaluate the association of AF with clinical factors, in-hospital mortality, hospitalization cost, and length of stay (LOS).

Results: We identified 2,578,165 patients who received prolonged MV (21.27% of AF patients). The prevalence of AF increased from 14.63% in 2008 to 24.43% in 2014 (p for trend < 0.0001). Amongst different phenotypes of critically ill patients, the prevalence of AF increased in patients with severe sepsis, asthma exacerbation, congestive heart failure exacerbation, acute stroke, and cardiac arrest. Older age, male sex, white race, medicare access, higher income, urban teaching hospital setting, and Western region were associated with a higher prevalence of AF. AF in critical illness was a risk factor for in-hospital death (odds ratio, 1.13; 95% confidence interval, 1.11 to 1.15), but in-hospital mortality in critically ill patients with AF decreased from 11.6% to 8.3%. AF was linked to prolonged LOS (2%, p < 0.0001) and high hospitalization cost (4%, p < 0.0001). LOS (-1%, p < 0.0001) and hospitalization cost (-4%, p < 0.0001) decreased yearly.

Conclusions: The prevalence of comorbid AF is increasing, particularly in older patients. AF may lead to poorer prognosis, and high-quality intensive care is imperative for this population.
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http://dx.doi.org/10.3904/kjim.2020.142DOI Listing
July 2021

Analysing wastewater to estimate fentanyl and tramadol use in major Chinese cities.

Sci Total Environ 2021 Jul 4;795:148838. Epub 2021 Jul 4.

Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Brisbane, Queensland 4102, Australia.

The misuse of fentanyl and more recently tramadol in the population has caused an opioid crisis in several countries and drawn much public attention worldwide. However, there is a gap of information on the potential misuse of fentanyl and tramadol in China. This study aims to fill this gap by analysing fentanyl and tramadol in wastewater of major cities across China to estimate their use. Wastewater samples were collected from 30 cities located across all seven geographic regions of China, from 2016 to 2019. Fentanyl was detected in only a few samples, suggesting a low prevalence of this potent opioid drug in China. Meanwhile, tramadol was found in most samples with concentrations ranging up to 186 ng/L. The per capita daily consumption of tramadol estimated from wastewater across China ranged from 6 mg/d/1000 in. to 213 mg/d/1000 inh. The consumption of tramadol seems to be similar among all the days of the week. Tramadol use is overall higher in Northeast China than in other regions, which is different from heroin, another popular opioid in China. Temporally, there is a significant decrease in tramadol use in major cities of China from 2016 to 2019. The results of our study suggested that tramadol use in China was predominantly from pharmaceutical prescription and not as prevalent as in other countries.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148838DOI Listing
July 2021

Prevalence, trends, and outcomes of atrial fibrillation in hospitalized patients with metastatic cancer: findings from a national sample.

Cancer Med 2021 Jul 7. Epub 2021 Jul 7.

Department of Health Statistics, Second Military Medical University, Shanghai, China.

Background: Epidemiological evidence regarding the link between cancer and atrial fibrillation (AF) are limited and outcomes of metastatic cancer comorbid with AF need to be elucidated.

Objective: This study aims to evaluate the prevalence, temporal trends, and outcomes of AF in hospitalized metastatic cancer patients.

Methods: The National Inpatient Sample (NIS) database was used to identify adult patients with metastatic tumors from 2003 to 2014. We analyzed the trends in AF prevalence, in-hospital mortality, total cost, length of stay (LOS), and comorbidities pertaining to metastatic cancer. Multivariable-adjusted models were used to evaluate the association of AF with clinical factors, in-hospital mortality, total cost, and LOS.

Results: Among 2,478,598 patients with metastatic cancer, 8.74% (216,737) were diagnosed with AF. The proportion of comorbid AF increased from 8.28% in 2003 to 10.06% in 2014 (p < 0.0001). Older age, white race, male, Medicare, higher income, larger hospital bed size, and urban teaching hospital were associated with higher AF occurrence. Among primary tumor sites, lung cancer experienced the highest odds of AF compared to other cancers. Patients with metastasis to lymph node and respiratory organ had higher odds of AF. In metastatic cancer, AF was associated with higher in-hospital mortality (odds ratio: 1.48; 95% confidence interval: 1.43-1.54), 18% longer LOS, and 19% higher cost.

Conclusions: AF prevalence in metastatic cancer continues to increase from 2003 to 2014. AF is linked to poorer prognosis and higher healthcare resource utilization. As the population ages, optimal preventive and treatment management strategies are needed for metastatic cancer comorbid with AF.
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http://dx.doi.org/10.1002/cam4.4105DOI Listing
July 2021

Identification of Ophiopogonis Radix from different producing areas by headspace-gas chromatography-ion mobility spectrometry analysis.

J Food Biochem 2021 Jul 5:e13850. Epub 2021 Jul 5.

Zhejiang Institute for Food and Drug Control, Hangzhou, China.

Ophiopogonis Radix can be divided into Zhemaidong (ZMD) and Chuanmaidong (CMD). The main planting areas of ZMD are Cixi City and Sanmen county. The quality and price of Ophiopogonis Radix from different producing areas are different. In this study, the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) method is used to rapidly identify ZMD and CMD. The method is also used to identify ZMD from Cixi and Sanmen by analyzing volatile organic compounds (VOCs). A total of 58 VOCs was obtained from ZMD samples with more abundant signals of which 41 were identified. The peak intensities of all VOCs in ZMD and CMD, Cixi and Sanmen data were averaged and then those VOCs whose peak intensities were distributed outside of mean ± 2 standard deviation (μ ± 2σ) were selected as characteristic markers. We selected 14 characteristic markers to establish the characteristic fingerprint of ZMD and CMD, among the 14 VOCs, ZMD contained more eucalyptus oil compounds than CMD, CMD contained more volatile aldehydes than ZMD. We selected 12 characteristic markers for the establishment of the characteristic fingerprint of ZMD from Cixi and Sanmen. The principal component analysis (PCA) results indicated that both ZMD and CMD or ZMD from Cixi and Sanmen could be effectively divided. The ZMD and CMD as well as ZMD from Cixi and Sanmen were evaluated by partial least squares regression-discriminants analysis (PLS-DA) resulting to be excellent chemical descriptors for sample discrimination. One hundred percent classification rates for both PLS-DA calibration and prediction models were obtained. These results provided a reference for the traceability of species and origin and market standard of Ophiopogonis Radix. PRACTICAL APPLICATIONS: Ophiopogonis Radix can be divided into Zhejiang Ophiopogonis Radix (ZMD) and Sichuan Ophiopogonis Radix (CMD). As far as ZMD is concerned, its producing areas mainly include the traditional planting areas (Cixi City) and new growth areas (Sanmen county). In this paper, the HS-GC-IMS method was adopted to analyze VOCs in Ophiopogonis Radix from different producing areas and then we screen out the respective characteristic VOCs of ZMD and CMD as well as ZMD from Cixi and Sanmen. These characteristic VOCs can effectively identify ZMD and CMD as well as ZMD from Cixi City and Sanmen country to provide a scientific basis for the origin identification of Ophiopogonis Radix.
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http://dx.doi.org/10.1111/jfbc.13850DOI Listing
July 2021

Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis.

Pharmacol Res 2021 Jul 1;170:105748. Epub 2021 Jul 1.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China; Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning 530020, China.

Pyroptosis, a type of programmed cell death (PCD), is characterized by cell swelling with bubbles, and the release of inflammatory cell cytokines. Cucurbitacin B (CuB), extracted from muskmelon pedicel, is a natural bioactive product that could effectively exert anti-tumor activities in lung cancer. However, the exact molecular mechanisms and the direct targets of CuB in non-small cell lung cancer (NSCLC) remain to be discovered. Here, we firstly found that CuB exerted an anti-tumor effect via pyroptosis in NSCLC cells and NSCLC mice models. Next, based on the molecular docking and cellular thermal shift assay (CETSA), we identified that CuB directly bound to Toll-like receptor 4 (TLR4) to activate the NLRP3 inflammasome, which further caused the separation of N- and C-terminals of Gasdermin D (GSDMD) to execute pyroptosis. Moreover, CuB enhanced the mitochondrial reactive oxygen species (ROS), mitochondrial membrane protein Tom20 accumulation, and cytosolic calcium (Ca) release, leading to pyroptosis in NSCLC cells. Silencing of TLR4 inhibited CuB-induced pyroptosis and decreased the level of ROS and Ca in A549 cells. In vivo study showed that CuB treatment suppressed lung tumor growth in mice via pyroptosis without dose-dependent manner, and CuB at 0.75 mg/kg had a better anti-tumor effect compared to the Gefitinib group. Taken together, our findings revealed the mechanisms and targets of CuB triggering pyroptosis in NSCLC, thus supporting the notion of developing CuB as a promising therapeutic agent for NSCLC.
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http://dx.doi.org/10.1016/j.phrs.2021.105748DOI Listing
July 2021

Freshwater quality criteria of four strobilurin fungicides: Interspecies correlation and toxic mechanism.

Chemosphere 2021 Jun 29;284:131340. Epub 2021 Jun 29.

State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, 130117, PR China. Electronic address:

Strobilurin fungicides are widely used pesticides in the world. They can have toxic effects not only to target organisms, but also to nontarget organisms. To assess their ecological risk, species sensitivity distributions (SSDs) are required for the development of water quality criteria (WQC). In this paper, the acute toxicity of four methoxyacrylate fungicides were experimentally determined and evaluated at 24, 48, 72 and 96 h for the species of Rana chensinensis and Limnodrilus hoffmeisteri, respectively. Acute and chronic HC (5% hazard concentration) values and WQC values were calculated from SSDs based on the toxicity values determined in this paper and compiled from literature. SSDs revealed that aquatic animals were relatively sensitive species and aquatic plants are insensitive species for the four fungicides. However, different orders of species sensitivity in the acute and chronic toxicity indicated that these four fungicides had different toxic mechanisms or mode of action (MOA) to different species. According to toxicity correlation and principal component analysis (PCA), the kresoxim-methyl toxicity was very close to trifloxystrobin as compared with others due to that they are neutral compounds with very similar physicochemical properties. Quantitative structure-activity relationship (QSAR) revealed that toxicity of strobilurin fungicides were dependent both on chemical hydrophobicity and hydrogen bond basicity. These two molecular descriptors reflect the bio-uptake process and interaction of compounds with target receptors in an organism. WQC values and interspecies correlation are valuable for assessing water quality and understanding toxic mechanisms to different species.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131340DOI Listing
June 2021

Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons.

Nat Commun 2021 07 1;12(1):4075. Epub 2021 Jul 1.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese academy of Science, Shanghai, 200032, China.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.
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http://dx.doi.org/10.1038/s41467-021-24236-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249382PMC
July 2021

Efficient Activation of Coal Fly Ash for Silica and Alumina Leaches and the Dependence of Pb(II) Removal Capacity on the Crystallization Conditions of Al-MCM-41.

Int J Mol Sci 2021 Jun 18;22(12). Epub 2021 Jun 18.

State Environmental Protection Key Laboratory of Eco-Industry, Northeastern University, Shenyang 110819, China.

In this study, four different coal fly ashes (CFAs) were used as raw materials of silica and alumina for the preparation of the alumina-containing Mobil Composition of Matter No. 41 (Al-MCM-41) and the exploration of an activation strategy that is efficient and universal for various CFAs. Alkaline hydrothermal and alkaline fusion activations proceeded at different temperatures to determine the best treatment parameters. We controlled the pore structure and surface hydroxyl density of the CFA-derived Al-MCM-41 by changing the crystallization temperature and aging time. The products were characterized by small-angle X-ray diffraction, nitrogen isotherms, Fourier-transform infrared spectroscopy, Si silica magic-angle spinning nuclear magnetic resonance, and transmission electron microscopy, and they were then grafted with thiol groups to remove Pb(II) from aqueous solutions. This paper innovatively evaluates the CFA activation strategies using energy consumption analysis and determines the optimal activation methodology and parameters. This paper also unveils the effect of the crystallization condition of Al-MCM-41 on its subsequent Pb(II) removal capacity. The results show that the appropriate selection of crystallization parameters can considerably increase the removal capacity over Pb(II), providing a new path to tackle the ever-increasing concern of aquic heavy-metal pollution.
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http://dx.doi.org/10.3390/ijms22126540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233738PMC
June 2021

Tanshinone I exerts cardiovascular protective effects in vivo and in vitro through inhibiting necroptosis via Akt/Nrf2 signaling pathway.

Chin Med 2021 Jun 28;16(1):48. Epub 2021 Jun 28.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.

Background: Tanshinone I (TI) is a primary component of Salvia miltiorrhiza Bunge (Danshen), which confers a favorable role in a variety of pharmacological activities including cardiovascular protection. However, the exact mechanism of the cardiovascular protection activity of TI remains to be illustrated. In this study, the cardiovascular protective effect and its mechanism of TI were investigated.

Methods: In this study, tert-butyl hydroperoxide (t-BHP)-stimulated H9c2 cells model was employed to investigate the protective effect in vitro. The cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) kit. The reactive-oxygen-species (ROS) level and mitochondrial membrane potential (MMP) were investigated by the flow cytometry and JC-1 assay, respectively. While in vivo experiment, the cardiovascular protective effect of TI was determined by using myocardial ischemia-reperfusion (MI/R) model including hematoxylin-eosin (H&E) staining assay and determination of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release were detected by Enzyme-linked immunosorbent assay (ELISA). Receptor interacting protein kinase 1 (RIP1), receptor interacting protein kinase 3 (RIP3), receptor interacting protein kinase 3 (MLKL), protein kinase B (Akt), Nuclear factor erythroid 2 related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were determined by western blotting.

Results: Our data demonstrated that TI pretreatment attenuated t-BHP and MI/R injury-induced necroptosis by inhibiting the expression of p-RIP1, p-RIP3, and p-MLKL. TI activated the Akt/Nrf2 pathway to promote the expression of antioxidant-related proteins such as phosphorylation of Akt, nuclear factor erythroid 2 related factor 2 (Nrf2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1) expression in t-BHP-stimulated H9c2 cells. TI relieved oxidative stress by mitigating ROS generation and reversing MMP loss. In vivo experiment, TI made electrocardiograph (ECG) recovery better and lessened the degree of myocardial tissue damage. The counts of white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), and the release of TNF-α and IL-6 were reversed by TI treatment. SOD level was increased, while MDA level was decreased by TI treatment.

Conclusion: Collectively, our findings indicated that TI exerted cardiovascular protective activities in vitro and in vivo through suppressing RIP1/RIP3/MLKL and activating Akt/Nrf2 signaling pathways, which could be developed into a cardiovascular protective agent.
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http://dx.doi.org/10.1186/s13020-021-00458-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240219PMC
June 2021

VAL genes regulate vegetative phase change via miR156-dependent and independent mechanisms.

PLoS Genet 2021 Jun 28;17(6):e1009626. Epub 2021 Jun 28.

Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

How organisms control when to transition between different stages of development is a key question in biology. In plants, epigenetic silencing by Polycomb repressive complex 1 (PRC1) and PRC2 plays a crucial role in promoting developmental transitions, including from juvenile-to-adult phases of vegetative growth. PRC1/2 are known to repress the master regulator of vegetative phase change, miR156, leading to the transition to adult growth, but how this process is regulated temporally is unknown. Here we investigate whether transcription factors in the VIVIPAROUS/ABI3-LIKE (VAL) gene family provide the temporal signal for the epigenetic repression of miR156. Exploiting a novel val1 allele, we found that VAL1 and VAL2 redundantly regulate vegetative phase change by controlling the overall level, rather than temporal dynamics, of miR156 expression. Furthermore, we discovered that VAL1 and VAL2 also act independently of miR156 to control this important developmental transition. In combination, our results highlight the complexity of temporal regulation in plants.
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http://dx.doi.org/10.1371/journal.pgen.1009626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270478PMC
June 2021

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets.

Front Nutr 2021 7;8:675640. Epub 2021 Jun 7.

Key Laboratory of Animal Nutrition in Jiangxi Province, Jiangxi Agricultural University, Nanchang, China.

This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing , and , and lactate-producing as well as , and were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.
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http://dx.doi.org/10.3389/fnut.2021.675640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215270PMC
June 2021

A single-cell-resolution fate map of endoderm reveals demarcation of pancreatic progenitors by cell cycle.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Institute of Developmental Biology and Regenerative Medicine, Southwest University, 400715 Chongqing, China;

A progenitor cell could generate a certain type or multiple types of descendant cells during embryonic development. To make all the descendant cell types and developmental trajectories of every single progenitor cell clear remains an ultimate goal in developmental biology. Characterizations of descendant cells produced by each uncommitted progenitor for a full germ layer represent a big step toward the goal. Here, we focus on early foregut endoderm, which generates foregut digestive organs, including the pancreas, liver, foregut, and ductal system, through distinct lineages. Using unbiased single-cell labeling techniques, we label every individual zebrafish foregut endodermal progenitor cell out of 216 cells to visibly trace the distribution and number of their descendant cells. Hence, single-cell-resolution fate and proliferation maps of early foregut endoderm are established, in which progenitor regions of each foregut digestive organ are precisely demarcated. The maps indicate that the pancreatic endocrine progenitors are featured by a cell cycle state with a long G1 phase. Manipulating durations of the G1 phase modulates pancreatic progenitor populations. This study illustrates foregut endodermal progenitor cell fate at single-cell resolution, precisely demarcates different progenitor populations, and sheds light on mechanistic insights into pancreatic fate determination.
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http://dx.doi.org/10.1073/pnas.2025793118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237672PMC
June 2021

Bibliometric Insights in Genetic Factors of Substance-Related Disorders: Intellectual Developments, Turning Points, and Emerging Trends.

Front Psychiatry 2021 31;12:620489. Epub 2021 May 31.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Substance-related disorders are a group of medical conditions that affect a person's brain and behavior and lead to an inability to control the use of legal or illegal drug(s) or medication. Substance-related disorder is a serious public health and society problem worldwide. Genetic factors have been proven to have an important role. Researchers have carried out a lot of work in this field, and a large number of research results have been published in academic journals around the world. However, there are few overviews of research progress, presentation, and development trends in this field. In this study, a total of 636 articles related to genetic factors of substance-related disorders were retrieved from the Web of Science (WoS) database from 1997 to 2018, and the scientific literatures were analyzed by bibliometrics. The study found that the United States (US) has maintained a leading position in the field of research, with many core institutions and plenty of high-quality research results. Alcohol use disorder is still the most concerning issue in this field. Over the past 20 years, new techniques such as genome-wide association study (GWAS) based on high-throughput sequencing technology have replaced family studies, twin studies, and retrospective studies in this field. We believe that it is urgent to study the genetic factors of substance-related disorders, which can greatly deepen the understanding of the pathogenesis of substance-related disorders and may provide potential targets for precise treatment of such diseases.
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http://dx.doi.org/10.3389/fpsyt.2021.620489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200466PMC
May 2021

Cardiovascular Disease Prediction by Machine Learning Algorithms Based on Cytokines in Kazakhs of China.

Clin Epidemiol 2021 9;13:417-428. Epub 2021 Jun 9.

Department of Public Health, Shihezi University School of Medicine, Shihezi, Xinjiang, People's Republic of China.

Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Accurately identifying subjects at high-risk of CVD may improve CVD outcomes. We sought to systematically examine the feasibility and performance of 7 widely used machine learning (ML) algorithms in predicting CVD risks.

Methods: The final analysis included 1508 Kazakh subjects in China without CVD at baseline who completed follow-up. All subjects were randomly divided into the training set (80%) and the test set (20%). L1-penalized logistic regression (LR), support vector machine with radial basis function (SVM), decision tree (DT), random forest (RF), k-nearest neighbors (KNN), Gaussian naive Bayes (NB), and extreme gradient boosting (XGB) were employed for prediction CVD outcomes. Ten-fold cross-validation was used during model developing and hyperparameters tuning in the training set. Model performance was evaluated in the test set in light of discrimination, calibration, and clinical usefulness. RF was applied to obtain the variable importance of included variables. Twenty-two variables, including sociodemographic characteristics, medical history, cytokines, and synthetic indices, were used for model development.

Results: Among 1508 subjects, 203 were diagnosed with CVD over a median follow-up of 5.17 years. All 7 models had moderate to excellent discrimination (AUC ranged from 0.770 to 0.872) and were well calibrated. LR and SVM performed identically with an AUC of 0.872 (95% CI: 0.829-0.907) and 0.868 (95% CI: 0.825-0.904), respectively. LR had the lowest Brier score (0.078) and the highest sensitivity (97.1%). Decision curve analysis indicated that SVM was slightly better than LR. The inflammatory cytokines, such as hs-CRP and IL-6, were identified as strong predictors of CVD.

Conclusion: SVM and LR can be applied to guide clinical decision-making in the Kazakh Chinese population, and further study is required to ensure their accuracies.
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http://dx.doi.org/10.2147/CLEP.S313343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200454PMC
June 2021

Calcium channel blockers improve prognosis of patients with coronavirus disease 2019 and hypertension.

Chin Med J (Engl) 2021 Jun 16;134(13):1602-1609. Epub 2021 Jun 16.

Department of Health Statistics, Naval Medical University, Shanghai 200433, China.

Background: Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.

Methods: We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.

Results: Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13-0.76, χ2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13-1.43, χ2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53-2.69, χ2 = 0.17, P = 0.6777).

Conclusions: In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.
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http://dx.doi.org/10.1097/CM9.0000000000001479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280095PMC
June 2021

Root cause determination of intraperitoneal catheter obstructions: Insulin amyloid aggregates vs foreign body reaction.

J Control Release 2021 Jun 10;336:1-15. Epub 2021 Jun 10.

Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Road U3092, Storrs, CT 06269, USA. Electronic address:

Continuous intraperitoneal insulin infusion, from an implanted insulin pump connected to a catheter that delivers insulin directly to the peritoneal cavity has many clinical advantages for patients with Type 1 diabetes. However, the ongoing incidence of catheter obstructions remains a barrier to the widespread use of this therapy. To date, the root cause of these obstructions remains unknown. Here, a two-year clinical investigation was conducted, along with the development of an animal model to enable a mechanistic investigation into this issue. This novel animal model was able to mimic the catheter obstructions that occur in patients and, fortuitously, at an accelerated rate. This model allowed for independent assessment of each potential cause associated with catheter obstructions to help identify the root cause. Both macroscopic and microscopic analysis were conducted with regards to the onset and progression of catheter obstructions, along with monitoring of insulin delivery. Interestingly, although insulin aggregation occurs in insulin pumps and insulin aggregates were found in some catheter obstructions, insulin is unlikely to be the root cause, since obstructions also occurred in the control groups where only diluent (no insulin) was administered to the animals. Inflammatory cells, different phenotypes of fibroblasts, as well as collagen were observed in all obstructed catheters explanted from the patients and the animals. The presence of these cells and collagen is indicative of a typical foreign body reaction. In addition, the dynamic change in the fibroblasts with respect to morphology, phenotype, and spatial distribution suggests that tissue irritation-mediated epithelial to mesenchymal transition plays a role in catheter obstructions.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.005DOI Listing
June 2021

Autophagy modulates FSS-induced epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Mol Carcinog 2021 Jun 9. Epub 2021 Jun 9.

Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

Hepatocellular carcinoma is a highly fatal disease and threatens human health seriously. Fluid shear stress (FSS), which is caused by the leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage, has been identified as contributing pathologically to cancer metastasis. Autophagy and epithelial-mesenchymal transition (EMT) are both reported to be involved in cancer cell migration and invasion, but little has been revealed about the interaction between autophagy and EMT under a tumor mechanical microenvironment. Here, we identified that exposure to 1.4 dyne/cm FSS could promote the formation of autophagosomes and significantly increase the expressions of autophagy-related markers of beclin1 and ATG7, and the ratio of LC3Ⅱ/Ⅰ in both of HepG2 and QGY-7703 cells. The FSS loading also elevated the levels of mesenchymal markers N-cadherin, Vimentin, Twist, Snail, and β-catenin, while the epithelial markers E-cadherin showed a decrease. Once the autophagy was blocked by 3-methyladenine (3-MA) or knocking ATG5 down, the occurrence of FSS-induced EMT was inhibited dramatically according to the expression and translocation of E-cadherin, N-cadherin, and β-catenin. Given the effect of EMT on cell migration, we observed that inhibition of autophagy could impede FSS-induced cell migration. Collectively, this study demonstrated that autophagy played a crucial role in FSS-induced EMT and cell migration in hepatocellular carcinoma.
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http://dx.doi.org/10.1002/mc.23327DOI Listing
June 2021

Efficient point-by-point Bragg grating inscription in sapphire fiber using femtosecond laser filaments.

Opt Lett 2021 Jun;46(11):2742-2745

Sapphire fiber Bragg gratings (SFBGs) inscribed by using femtosecond laser point-by-point (PbP) technology typically have an extremely low reflectivity due to the limited cross-sectional area of refractive index modulations (RIMs) created in sapphire fiber. Hence, we propose and experimentally demonstrate a filamentation process for fabricating PbP SFBGs. This approach provides an efficient method for producing SFBGs at various Bragg wavelengths with a higher reflectivity, since the filament tracks could enlarge the cross-sectional area of RIMs. The influences of the pulse energy and the focal depth on the generation and morphology of the filament tracks were studied, and after optimizing these parameters, high-quality filament tracks with a length of 90 µm and a width of 1.4 µm were produced into sapphire fiber with a diameter of 100 µm. These filament tracks were precisely assembled in sapphire fiber, generating an SFBG with a reflectivity of 2.3%. The total fabrication time for this SFBG only requires ${\sim}{1.1}\;{\rm s}$. Subsequently, a wavelength-division-multiplexed (WDM) SFBG array consisting of five SFBGs was efficiently constructed. Moreover, the high-temperature response of the SFBG array was investigated and the experimental results showed that the SFBG array can withstand a high temperature of 1600°C. Such a WDM SFBG array could serve as quasi-distributed high-temperature sensor which will be promising in many areas, i.e., metallurgical, chemical, and aviation industries.
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http://dx.doi.org/10.1364/OL.426407DOI Listing
June 2021

[Establishment and evaluation of hepatocyte injury model induced by LPS/D-galactosamine in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jun;37(6):495-500

Institute of Military Cognition and Brain Science, Academy of Military Medical Sciences, Beijing 100850, China. *Corresponding author, E-mail:

Objective To establish a novel hepatocyte injury model induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in vitro. Methods Freshly isolated mouse primary hepatocytes were cultured in vitro and treated with different doses of tumor necrosis factor-α (TNF-α) and 5 mg/mL of D-GalN. The supernatants from hepatocyte culture were detected for alanine aminotransferase (ALT) activity by chemiluminescence assay. Bone marrow-derived macrophages (BMDMs) were stimulated with 1 μg/mL of LPS and the level of TNF-α in supernatants were detected by ELISA. Primary hepatocytes were treated with the BMDM supernatants combined with 5 mg/mL D-GalN or 50 ng/mL actinomycin D (ActD) for 24 hours. The level of ALT from hepatocyte supernatant was detected and morphology of hepatocytes was observed with microscopy. BMDMs and hepatocytes were co-cultured and treated with 1 μg/mL of LPS combined with D-GalN or ActD for 24 hours. Hepatocyte injury was reflected by the ALT activity and hepatocyte morphology. Results The ALT activity was significantly increased in the supernatants of hepatocytes treated with TNF-α and D-GalN, indicating the obvious hepatocyte injury. Co-treatment with LPS-primed BMDM supernatants and D-GalN or ActD could cause hepatocyte injury, as reflected by markedly increased ALT activity and the deformed and cracked hepatocytes. In the context of co-culture of BMDM and hepatocytes, treatment with LPS and D-GalN led to obvious hepatocyte injury as expected. LPS combined with ActD could not cause hepatocyte injury, since the BMDMs started to die earlier than they could secret TNF-α to destruct hepatocytes. Hepatocytes with normal morphology and deformed BMDMs were observed. Conclusion LPS/D-GalN can be used to induce hepatocyte injury in vitro. D-GalN, rather than ActD, should be used as a transcriptional inhibitor when the TNF-α -induced hepatocyte injury is evaluated in a co-culture system of BMDMs and hepatocytes.
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June 2021

Identification of changes in volatile organic compounds in Ophiopogonis Radix containing spoiled products in different proportions by headspace-gas chromatography-ion mobility spectrometry.

J Food Biochem 2021 May 26:e13802. Epub 2021 May 26.

Zhejiang Institute for Food and Drug Control, Hangzhou, China.

Ophiopogonis Radix is a kind of traditional Chinese medicine as well as a type of functional food. Because Ophiopogonis Radix grows in the ground, it is often damaged by worms during planting or broken when people try to dig them out, which leads to the containments of spoiled products of different proportion in Ophiopogonis Radix. Volatile organic compounds (VOCs) in Ophiopogonis Radix, which involves spoiled products in different proportions, were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Finally, a total of 87 VOCs were discovered after analysis, and 14 of them were chose to established characteristic fingerprints. Twelve of the 14 characteristic compounds were be recognized by a built-in database. The results showed that the content of hexanol, ethanol, methanol, (E)-2-hexenal, and hexanal was in inverse proportion with the containing of spoiled products, so they may be characteristic VOCs of fresh Ophiopogonis Radix,; and the content of 3-methy-1-butanol, furfural, 5-methylfural, phenylacetaldehyde, 2-methylbutanoic acid, 2-butanone, and 2-acetylfuran are proportional to the containing of spoiled products, so they may be the characteristic of VOCs of spoiled Ophiopogonis Radix. The signal peak intensities of the 14 characteristic VOCs were used as the variables of principal component analysis (PCA). The result shows that the fresh Ophiopogonis Radix and the spoiled Ophiopogonis Radix could be clearly differentiated, and the different proportions of spoiled products were grouped into separate categories, respectively. The larger the proportion of spoiled products, the greater the difference between the sample and fresh Ophiopogonis Radix. PRACTICAL APPLICATIONS: Ophiopogonis Radix is a kind of commonly used traditional Chinese medicine and functional food. In the actual use of Ophiopogonis Radix, the damage caused by worms during planting and the breakage during being dug out often lead to Ophiopogonis Radix containing spoiled products in the market. The existence of spoiled products greatly affects the quality and safety of Ophiopogonis Radix. Due to the difference in flavor between fresh Ophiopogonis Radix and spoiled products, the present study used HS-GC-IMS method to analyze the VOCs in fresh Ophiopogonis Radix and Ophiopogonis Radix containing spoiled products of different proportions and screened out the characteristic VOCs of fresh Ophiopogonis Radix and spoiled Ophiopogonis Radix. The results provide scientific basis for quality control of Ophiopogonis Radix.
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http://dx.doi.org/10.1111/jfbc.13802DOI Listing
May 2021

A phase I, single and continuous dose administration study on the safety, tolerability, and pharmacokinetics of neorudin, a novel recombinant anticoagulant protein, in healthy subjects.

Pharmacol Res Perspect 2021 May;9(3):e00785

Beijing Institute of Radiation Medicine, Beijing, China.

The aim of this study was to evaluate the tolerability, safety, and pharmacokinetics of single and continuous dose administration of recombinant neorudin (EPR-hirudin, EH) by intravenous administration in healthy subjects, and to provide a safe dosage range for phase II clinical research. Forty-four subjects received EH as a single dose of between 0.2 and 2.0 mg/kg by intravenous bolus and drip infusion. In addition, 18 healthy subjects were randomly divided into three dose groups (0.15, 0.30, and 0.45 mg/kg/h) with 6 subjects in each group for the continuous administration trial. Single or continuous doses of neorudin were generally well tolerated by healthy adult subjects. There were no serious adverse events (SAEs), and all adverse events (AEs) were mild to moderate. Moreover, no subjects withdrew from the trial because of AEs. There were no clinically relevant changes in physical examination results, clinical chemistry, urinalysis, or vital signs. The incidence of adverse events was not significantly related to drug dose or systemic exposure. After single-dose and continuous administration, the serum EH concentration reached its peak at 5 min, and the exposure increased with the increase in the administered dose. The mean half-life (T ), clearance (Cl), and apparent volume of distribution (Vd) of EH ranged from 1.7 to 2.5 h, 123.9 to 179.7 ml/h/kg, and 402.7 to 615.2 ml/kg, respectively. The demonstrated safety, tolerability, and pharmacokinetic characteristics of EH can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies. Clinical trial registration: Chinadrugtrials.org identifier: CTR20160444.
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http://dx.doi.org/10.1002/prp2.785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101608PMC
May 2021

Expression of RAB7L1 in Patients with Pituitary Adenomas.

Ann Clin Lab Sci 2021 Mar;51(2):190-197

Department of Neurosurgery, TheFirst Affiliated Hospital of Soochow University, Suzhou, China.

Pituitary adenomas (PA) are neoplasms that arise predominantly in the adenohypophysis. They are generally divided into three categories depending on their biological behavior: benign adenomas, invasive adenomas, and carcinomas. They represent 10%-25% of all intracranial neoplasms, and their estimated prevalence in the general population is 17%. RAB7L1, located at the PARK16 locus, is a Rab GTPase key regulator in vesicle trafficking. Recent genome-wide association studies have linked variants in RAB7L1 to the risk of Parkinson's disease. However, the association between RAB7L1 and PAs is still unexplored. Thirty patients with pituitary adenomas who had undergone surgical resection at Jiangyin People's Hospital (Jiangsu, China) from 2014 to 2019 were selected. The RAB7L1 expression level was assessed by qPCR, Western blot, and immunohistochemical staining. The level of the RAB7L1 differential expression was closely related to the patients' age and size of the PAs. In contrast, the RAB7L1 expression level was found to be unrelated to gender, Knosp classification, or type of PA. Our study found that the RAB7L1 expression level was higher in adenoma tissues from older PA patients, and the RAB7L1 expression level was higher in adenoma tissues from patients with smaller adenomas (size≤2cm) than those with larger adenomas (size>2cm).
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March 2021

Application of Redox-Responsive Hydrogels Based on 2,2,6,6-Tetramethyl-1-Piperidinyloxy Methacrylate and Oligo(Ethyleneglycol) Methacrylate in Controlled Release and Catalysis.

Polymers (Basel) 2021 Apr 16;13(8). Epub 2021 Apr 16.

Institute of Condensed Matter and Nanosciences (IMCN), Université catholique de Louvain, Place L. Pasteur 1, B-1348 Louvain-la-Neuve, Belgium.

Hydrogels have reached momentum due to their potential application in a variety of fields including their ability to deliver active molecules upon application of a specific chemical or physical stimulus and to act as easily recyclable catalysts in a green chemistry approach. In this paper, we demonstrate that the same redox-responsive hydrogels based on polymer networks containing 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) stable nitroxide radicals and oligoethylene glycol methyl ether methacrylate (OEGMA) can be successfully used either for the electrochemically triggered release of aspirin or as catalysts for the oxidation of primary alcohols into aldehydes. For the first application, we take the opportunity of the positive charges present on the oxoammonium groups of oxidized TEMPO to encapsulate negatively charged aspirin molecules. The further electrochemical reduction of oxoammonium groups into nitroxide radicals triggers the release of aspirin molecules. For the second application, our hydrogels are swelled with benzylic alcohol and tert-butyl nitrite as co-catalyst and the temperature is raised to 50 °C to start the oxidation reaction. Interestingly enough, benzaldehyde is not miscible with our hydrogels and phase-separate on top of them allowing the easy recovery of the reaction product and the recyclability of the hydrogel catalyst.
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http://dx.doi.org/10.3390/polym13081307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073720PMC
April 2021

Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study.

Seizure 2021 May 15;88:138-142. Epub 2021 Apr 15.

The Second Affiliated Hospital of Harbin Medical University, China. Electronic address:

Background: To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE.

Methods: A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups.

Results: In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE.

Conclusion: Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.
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http://dx.doi.org/10.1016/j.seizure.2021.04.010DOI Listing
May 2021

Visceral Obesity-Related Indices in the Identification of Individuals with Metabolic Syndrome Among Different Ethnicities in Xinjiang, China.

Diabetes Metab Syndr Obes 2021 12;14:1609-1620. Epub 2021 Apr 12.

Department of Public Health, Shihezi University School of Medicine, Shihezi, Xinjiang, People's Republic of China.

Background: Few studies have focused on the predictive ability of visceral obesity-related indices for metabolic syndrome (MetS), especially in different ethnic groups. This study aimed to evaluate the applicability of visceral obesity-related indices for MetS screening among three major ethnic groups living in remote rural areas of Xinjiang.

Methods: Based on multistage stratified cluster random sampling method, 3,192 Uyghurs, 3,054 Kazakhs, and 3,658 Hans were recruited from Xinjiang, China. The Joint Interim Statement (JIS) criteria were used to define MetS. The receiver operating characteristic curve (ROC), area under the ROC curve (AUC), and predictive value of each visceral obesity-related index were used to evaluate the predictive ability of MetS.

Results: After adjusting for potential confounding factors, the lipid accumulation product (LAP), Chinese visceral adiposity index (CVAI), waist-to-height ratio (WHtR), and atherogenic index of plasma (AIP) were significantly correlated with MetS for each ethnic group, and the odds ratios (ORs) for MetS increased across quartiles. LAP was best able to identify MetS status in Kazakhs (AUC=0.853) and Uyghurs (AUC=0.851), with optimal cut-offs being 36.3 and 28.2, respectively. Both LAP (AUC=0.798) and CVAI (AUC=0.791) most accurately identified MetS status in Hans, with the optimal cut-offs being 27.3 and 85.0, respectively. Moreover, the AUC of the combination of these visceral obesity-related indices is higher for each ethnic group. However, compared with LAP, the improved value of combined screening was not significant.

Conclusion: LAP had the best discriminative capability for the screening of MetS among Kazakhs, Uyghurs, and Hans. The screening ability of CVAI for MetS was similar to that of LAP in Hans. Thus, LAP may be a complementary indicator for assessing MetS in various ethnic groups.
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http://dx.doi.org/10.2147/DMSO.S306908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055644PMC
April 2021

Oleuropein Attenuates Lipopolysaccharide-Induced Acute Kidney Injury and by Regulating Toll-Like Receptor 4 Dimerization.

Front Pharmacol 2021 24;12:617314. Epub 2021 Mar 24.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.

Acute kidney injury (AKI) is a common critical illness that involves multiple systems and multiple organs with a rapid decline in kidney function over short period. It has a high mortality rate and presents a great treatment challenge for physicians. Oleuropein, the main active constituent of Hook. et Arn. var. kwangsiensis Hand.-Mazz. displays significant anti-inflammatory activity, although oleuropein's therapeutic effect and mechanism of action in AKI remain to be elucidated. The present study aimed to further clarify the mechanism by which oleuropein exerts effects on inflammation and . , the inflammatory effect and mechanism were investigated through ELISA, Western blotting, the thermal shift assay, co-immunoprecipitation, and immunofluorescence staining. Lipopolysaccharide (LPS) induced acute kidney injury was employed in an animal model to investigate oleuropein's therapeutic effect on AKI and mechanism . The underlying mechanisms were investigated by Western blot analysis of kidney tissue. In LPS-stimulated macrophages, our data demonstrated that oleuropein significantly reduced the expression of inflammatory mediators like NO, IL-6, TNF-α, iNOS, and COX-2. Moreover, oleuropein inhibited NF-κB/p65 translocation, and had a negative regulatory effect on key proteins in the NF-κB and MAPK pathways. In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88. Oleuropein markedly alleviated LPS induced acute kidney injury, decreased serum creatinine and blood urea nitrogen (BUN) levels and proinflammatory cytokines. More importantly, the TLR4-MyD88-NF-κB/MAPK pathways were confirmed to play an important role in the oleuropein treatment of AKI. In this study, oleuropein exhibited excellent anti-inflammatory effects by regulating TLR4-MyD88-NF-κB/MAPK axis and , suggesting oleuropein as a candidate molecule for treating AKI.
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http://dx.doi.org/10.3389/fphar.2021.617314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024564PMC
March 2021
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