Publications by authors named "Dan Gao"

185 Publications

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice.

Curr Med Sci 2021 Apr 20;41(2):279-286. Epub 2021 Apr 20.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.

Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD), and amyloid-β (Aβ) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains. This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration. Here, we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage, and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests, and investigated the possible mechanisms by immunohistochemistry and Western blotting. Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test. Furthermore, Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique. Finally, Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβ plaque deposition in the cortex and hippocampus of mice. These results reveal the beneficial effects of TSG in APP/PS1-AD mice, which may be associated with the reduction of Aβ deposits in the brain.
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http://dx.doi.org/10.1007/s11596-021-2344-zDOI Listing
April 2021

Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration.

Cell Rep 2021 Mar;34(13):108922

Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, Guangdong 510632, China. Electronic address:

Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.
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http://dx.doi.org/10.1016/j.celrep.2021.108922DOI Listing
March 2021

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

Alzheimers Res Ther 2021 03 17;13(1):62. Epub 2021 Mar 17.

Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China.

Background: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored.

Results: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.

Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.

Trial Registration: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.
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http://dx.doi.org/10.1186/s13195-021-00795-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967962PMC
March 2021

Chinese American children's temperamental shyness and responses to peer victimization as moderated by maternal praise.

J Fam Psychol 2021 Mar 11. Epub 2021 Mar 11.

School of Psychology and Cognitive Science.

This study examined the relations between Chinese American children's temperamental shyness and their assertive and submissive responses to peer victimization. The mediating role of children's anxious-withdrawn behavior in the association between their temperamental shyness and responses to peer victimization in school settings was assessed, as well as the moderating effect of observed maternal praise. Mothers of 153 Chinese American children (46.4% boys; = 4.40 years, = 0.79 years) reported on their children's temperamental shyness, and teachers rated children's display of anxious-withdrawn behavior and responses to peer victimization. Mothers' use of praise during their interactions with children in a free-play session was observed. Results showed that children's display of anxious-withdrawn behavior played a mediating role in the associations between their temperamental shyness and responses to peer victimization. Moreover, maternal praise moderated the relation between children's temperamental shyness and anxious-withdrawn behavior, such that more temperamentally shy children with mothers who used to praise more frequently displayed less anxious-withdrawn behavior, which, in turn, was associated with more assertiveness and less submissiveness in response to peer victimization. These findings highlight the importance of maternal praise in reducing children's display of anxious-withdrawn behavior, which in turn facilitates their capacity to cope with peer victimization. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000831DOI Listing
March 2021

Regional differences in genes and variants causing retinitis pigmentosa in Japan.

Jpn J Ophthalmol 2021 Feb 25. Epub 2021 Feb 25.

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Purpose: To investigate the regional differences in the genes and variants causing retinitis pigmentosa (RP) in Japan STUDY DESIGN: Retrospective multicenter study METHODS: In total, 1204 probands of each pedigree clinically diagnosed with nonsyndromic RP were enrolled from 5 Japanese facilities. The regions were divided into the Tohoku region, the Kanto and Chubu regions, and the Kyushu region according to the location of the hospitals where the participants were enrolled. We compared the proportions of the causative genes and the distributions of the pathogenic variants among these 3 regions.

Results: The proportions of genetically solved cases were 29.4% in the Tohoku region (n = 500), 29.6% in the Kanto and Chubu regions (n = 196), and 29.7% in the Kyushu region (n = 508), which did not differ statistically (P = .99). No significant regional differences in the proportions of each causative gene in genetically solved patients were observed after correction by multiple testing. Among the 29 pathogenic variants detected in all 3 regions, only p.(Pro347Leu) in RHO was an autosomal dominant variant; the remaining 28 variants were found in autosomal recessive genes. Conversely, 78.6% (275/350) of the pathogenic variants were detected only in a single region, and 6 pathogenic variants (p.[Asn3062fs] in EYS, p.[Ala315fs] in EYS, p.[Arg872fs] in RP1, p.[Ala126Val] in RDH12, p.[Arg41Trp] in CRX, and p.[Gly381fs] in PRPF31) were frequently found in ≥ 4 patients in the single region.

Conclusion: We observed region-specific pathogenic variants in the Japanese population. Further investigations of causative genes in multiple regions in Japan will contribute to the expansion of the catalog of genetic variants causing RP.
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http://dx.doi.org/10.1007/s10384-021-00824-wDOI Listing
February 2021

Corrigendum: Inflammatory Stress Potentiates Emodin-Induced Liver Injury in Rats.

Front Pharmacol 2020 25;11:597772. Epub 2021 Jan 25.

China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, China.

[This corrects the article DOI: 10.3389/fphar.2015.00233.].
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http://dx.doi.org/10.3389/fphar.2020.597772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869054PMC
January 2021

Cross-lagged panel analyses of maternal psychological control and young adolescents' emotion regulation.

J Adolesc 2021 Feb 19;87:52-62. Epub 2021 Jan 19.

School of Psychology and Cognitive Science, East China Normal University, China; Shanghai Changning Mental Health Center, Shanghai, China. Electronic address:

Introduction: The present study examined the longitudinal relations between maternal psychological control and emotion regulation in Chinese adolescents. Specifically, we examined how emotion regulation was reciprocally associated with multiple dimensions of psychological control, including love withdrawal, guilt induction, and shaming in the Chinese cultural context.

Methods: Participants consisted of 865 Chinese students from fourth through eighth grade (50.8% girls; M = 11.82 years at Wave 1, SD = 1.28 at Wave 1, range = 10-15 years). Data were collected at two time-periods over a one-year period. Children reported on their emotion regulation. Mothers rated their engagement in love withdrawal, guilt induction, and shaming.

Results: Cross-lagged panel analyses revealed an adequate model fit. Children's emotion regulation at study onset predicted decreases in all three dimensions of maternal psychological control one year later, whereas the three dimensions of maternal psychological control did not significantly predict emotion regulation one year later.

Conclusions: Findings revealed the longitudinal associations among child emotion regulation and maternal psychological control within a specific cultural context. Implications for the meaning of psychological control parenting in Chinese culture are discussed.
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http://dx.doi.org/10.1016/j.adolescence.2021.01.001DOI Listing
February 2021

Colorimetric glucose sensing with multiple-color changes by using a MnO NSs-TMB nanosystem.

Anal Methods 2021 02 18;13(6):769-775. Epub 2021 Jan 18.

State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, China.

Glucose performs many essential functions associated with metabolic processes in the living system, and is closely related to many diseases such as diabetes and hypoglycemia. Most of the existing glucose concentration detection methods require complex instruments, which undoubtedly limit its widespread use. Here, we have designed a glucose colorimetric detection system composed of glucose, glucose oxidase (GOD), manganese dioxide nanosheets (MnO NSs) and 3,3',5,5'-tetramethylbenzidine (TMB) to achieve colorimetric detection with the naked eye. Compared with the single-color change of the colorimetric method in previous studies, multiple-color changes have been realized. MnO NSs, as a kind of nanomaterial imitating oxidase, can directly oxidize TMB to oxTMB. Because oxTMB showed a dark yellow color when strongly oxidized and light blue when weakly oxidized, this feature can achieve multiple-color changes rather than a single-color change, which is helpful for colorimetric observation with the naked eye. Finally, we successfully used MnO NSs for colorimetric detection of glucose and realized multiple-color changes, making it easier to achieve colorimetric observation with the naked eye. The linear detection range is 0-4000 μM and limit of detection is 5.0 μM. This is not only useful for glucose, but also has an important significance for other experiments considering colorimetric experiments with the naked eye.
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http://dx.doi.org/10.1039/d0ay02184aDOI Listing
February 2021

Longitudinal study of the effects of occupational aluminium exposure on workers' cognition.

Chemosphere 2021 May 8;271:129569. Epub 2021 Jan 8.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address:

Objective: To explore the effects of occupational aluminium(Al) exposure on workers' cognition through a longitudinal study.

Methods: The study population consisted of 276 workers in an Al factory. In 2014, we used inductively coupled plasma mass spectrometry (ICP-MS) to determine the plasma aluminium (P-Al) concentration of the workers, and a combined questionnaire to test the workers' cognitive function. Followed-up in 2016, the workers were tested again for cognitive function. Generalized linear regression was used to assess the association between P-Al concentration and cognitive scores, and multivariable logistic regression was used to assess the risk of cognitive decline caused by Al exposure.

Results: Generalized linear regression results showed that a non-significant association was found between the P-Al concentration and cognitive test scores (P > 0.05) in 2014. Two years later, each 10-fold increase in P-Al concentration was inversely associated with the score of Mini-Mental state examination (MMSE) (β: -0.53, 95% CI: -0.86, -0.20) and Fuld object memory evaluation (FOME) (β: -0.93, 95% CI: -1.62, -0.24). Each 10-fold increase in P-Al concentration was inversely associated with MMSE (β: -0.38, 95% CI: -0.74, -0.01) and FOME (β: -1.20, 95% CI: -1.95, -0.45). There was a statistically significant difference in the average annual rate of change of MMSE and FOME with the tertile of P-Al concentration increase (P < 0.05). The multivariable logistic regression results showed that as the P-Al concentration increased, the risk of a FOME score decline increased (P = 0.009).

Conclusions: Continuous occupational Al exposure can damage workers' overall cognitive ability, especially episodic memory function.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129569DOI Listing
May 2021

Effects of ferric-phosphate forms on phosphorus release and the performance of anaerobic fermentation of waste activated sludge.

Bioresour Technol 2021 Mar 28;323:124622. Epub 2020 Dec 28.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

Five ferric-phosphate (Fe(III)Ps) with amorphous or crystalline structures were added to waste activated sludge (WAS) for anaerobic fermentation, aiming to investigate effects of Fe(III)Ps forms on phosphorus (P) release and the performance of WAS fermentation. The results revealed that the Fe(III) reduction rate of hexagonal-FePO was faster than that of monoclinic-FePO·2HO, thanks to its lower crystal field stabilization energy. FePO·nHO was reduced to vivianite and part of the phosphate was released as orthophosphate (PO-P). Giniite (Fe(PO)(OH)·2HO) as an iron hydroxyphosphate was transformed to βFe(III)Fe(II)(PO)O-like compounds without PO-P release. In addition, Fe(III)Ps had an adverse effect on the anaerobic fermentation of WAS. The specific hydrolysis rate constant and volatile fatty acids (VFAs) yield decreased by 38.4% and 41.9%, respectively, for the sludge sample with amorphous-FePO·3HO, which dropped the most. This study provides new insights into various forms of Fe(III)Ps performance during anaerobic fermentation and is beneficial to enhancing P recovery efficiency.
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http://dx.doi.org/10.1016/j.biortech.2020.124622DOI Listing
March 2021

Cross-sectional study based on occupational aluminium exposure population.

Environ Toxicol Pharmacol 2021 Apr 4;83:103581. Epub 2021 Jan 4.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China. Electronic address:

To evaluate the different characteristics of cognitive impairment caused by occupational aluminium exposure at different ages, we surveyed 1660 workers in Shanxi Aluminium Plant, China, and assessed their cognitive function and plasma aluminium concentration. In multiple linear regression, the scores of the digit-span test (DST) and digit-span backward test (DSBT) were negatively correlated with plasma aluminium concentration when concentration reached 34.52 μg/L in younger group (<40 years), while in the middle-aged group (≥40 years) only found when concentration reached 42.25 μg/L (β<0, P < 0.05). In logistic regression, when plasma aluminum concentration reached 42.25μg/L, odds ratios (95 % confidence interval) were 1.695 (1.062-2.705) and 3.270 (1.615-6.620) for DST, 7.644 (3.846-15.192) and 15.308 (4.180-56.059) for DSBT in middle-aged group and younger group, respectively. These results showed that aluminium exposures were associated with cognitive impairment among aluminium-exposed workers, particularly for young workers who were more susceptible.
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http://dx.doi.org/10.1016/j.etap.2020.103581DOI Listing
April 2021

Evaluation of the Antiwrinkle Activity of Enriched Isatidis Folium Extract and an HPLC-UV Method for the Quality Control of Its Cream Products.

Plants (Basel) 2020 Nov 16;9(11). Epub 2020 Nov 16.

College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.

Currently, many extracts from natural sources are added to cosmetic products for reducing facial aging and wrinkles. This study investigated the antiwrinkle activity of enriched extract of Isatidis Folium used for a novel antiwrinkle cream product. The result demonstrated that this enriched extract has excellent antiwrinkle activity by significantly inhibiting mRNA expression of matrix metalloproteinase-1, matrix metalloproteinase-3, and pro-inflammatory cytokines IL-1β and upregulating the mRNA expression of IL-4 and procollagen. Additionally, to implement effective quality control of the entire manufacturing process of antiwrinkle cream products based on the enriched extract of Isatidis Folium, the main chemical constituents of the enriched extract of Isatidis Folium was evaluated by high-performance liquid chromatography-photodiode array-tandem mass spectrometry (HPLC-PDA-ESI-MS/MS), five constituents were undisputedly confirmed. An HPLC-UV method in 15-min analysis time for quality assessment of the entire manufacturing process of antiwrinkle cream products was proposed and validated. The optimal conditions for extracting TMCA (3,4,5-trimethoxycinnamic acid) from the developed antiwrinkle cream products were determined using response surface methodology based on central composite design. The established HPLC method and optimal extract condition are suitable for routinely analyzing this novel antiwrinkle cream product.
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http://dx.doi.org/10.3390/plants9111586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698272PMC
November 2020

Streaming-enhanced, chip-based biosensor with acoustically active, biomarker-functionalized micropillars: A case study of thrombin detection.

Talanta 2021 Jan 13;222:121480. Epub 2020 Aug 13.

State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China.

Enzyme-linked immunosorbent assay is a widely used analytical technique for detecting and quantifying disease-specific protein biomarkers. Despite recent progresses in disease-specific protein biomarkers detection with microfluidic chips, many devices still suffer from the limited mass transport of target molecules, and consequently low detection efficiency or long incubation time. In this work, we present a novel strategy to significantly enhance the sensing efficiency of a chip-based biosensor by exploiting micro-streaming in an acoustofluidic device, which boosts intermolecular interactions and a hybridization chain reaction to increase the fluorescent signals. This device was made of a microfluidic chip that contains an array of PDMS micropillars in a ship-shaped microchannel. And the inner surface of the channel was functionalized with capture aptamers that bind with thrombin, chosen as a model target molecule. An ultrasonic transducer underneath the chip operating at 150 kHz generates circular micro-streaming flows around the pillars that significantly improves the binding efficiency of thrombin with capture aptamers by 1) increasing the retention time and 2) enhancing mass transport via local convection versus diffusion. The effects of ultrasound parameters, such as operating frequencies and voltages, on the distribution and magnitude of flows were optimized to obtain a better performance of the sensor chip. Under the optimized conditions, the detection limit was increased by one order of magnitude. Although this work has focused on the detection of thrombin as a model molecule, this streaming-enhanced, microstructure-based sensing strategy can be applied to detect a wide range of molecules or even cells.
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http://dx.doi.org/10.1016/j.talanta.2020.121480DOI Listing
January 2021

Alterations of the Human Gut Microbiome in Chronic Kidney Disease.

Adv Sci (Weinh) 2020 Oct 2;7(20):2001936. Epub 2020 Sep 2.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease National Clinical Research Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China.

Gut microbiota make up the largest microecosystem in the human body and are closely related to chronic metabolic diseases. Herein, 520 fecal samples are collected from different regions of China, the gut microbiome in chronic kidney disease (CKD) is characterized, and CKD classifiers based on microbial markers are constructed. Compared with healthy controls (HC, = 210), gut microbial diversity is significantly decreased in CKD ( = 110), and the microbial community is remarkably distinguished from HC. Genera and are enriched, while and are reduced in CKD. Fifty predicted microbial functions including tryptophan and phenylalanine metabolisms increase, while 36 functions including arginine and proline metabolisms decrease in CKD. Notably, five optimal microbial markers are identified using the random forest model. The area under the curve (AUC) reaches 0.9887 in the discovery cohort and 0.9512 in the validation cohort (49 CKD vs 63 HC). Importantly, the AUC reaches 0.8986 in the extra diagnosis cohort from Hangzhou. Moreover, and are increased with CKD progression. Thirteen operational taxonomy units are correlated with six clinical indicators of CKD. In conclusion, this study comprehensively characterizes gut microbiome in non-dialysis CKD and demonstrates the potential of microbial markers as non-invasive diagnostic tools for CKD in different regions of China.
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http://dx.doi.org/10.1002/advs.202001936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578882PMC
October 2020

LGR5 constitutively activates NF-κB signaling to regulate the growth of intestinal crypts.

FASEB J 2020 11 1;34(11):15605-15620. Epub 2020 Oct 1.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Mammalian LGR5 and LGR4, markers of adult stem cells, are involved in many physiological functions by enhancing WNT signaling. However, whether LGR5 and LGR4 are coupled to other intracellular signaling pathways to regulate stem cell function remains unknown. Here, we show that LGR5 and LGR4 can constitutively activate NF-κB signaling in a ligand-independent manner, which is dependent on their C-termini, but independent of receptor endocytosis. Moreover, the C-termini of LGR5/4 interact with TROY, which is required for activating NF-κB signaling. In small intestinal crypt organoids, overexpression of a C-terminal deletion mutant of LGR5 inhibits the growth and bud formation of organoids, whereas overexpression of the R-spondin-binding mutant of LGR5 that is defective for WNT signaling can still promote organoid growth. Our study reveals that NF-κB signaling, regulated by LGR5 and LGR4, plays an important role in the survival of colon cancer cells and the growth of intestinal crypts. Our findings also suggest that LGR5/4-induced NF-κB signaling and WNT signaling may co-regulate the growth of LGR5 adult stem cells and intestinal crypts.
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http://dx.doi.org/10.1096/fj.202001329RDOI Listing
November 2020

Isolation of bioactive components with soluble epoxide hydrolase inhibitory activity from MiQ. by ultrasonic-assisted extraction optimized using response surface methodology.

Prep Biochem Biotechnol 2021 17;51(4):395-404. Epub 2020 Sep 17.

College of Pharmacy, Chungnam National University, Daejeon, South Korea.

MiQ (SSM) is an important food and medicinal herb in Korea, used to improve memory of patients with senile dementia and cardiovascular diseases. However, little information on bioactive components from SSM or standardized extraction methods for these components is available. This study isolated and purified major components from SSM for the first time, and assessed their ability to inhibit soluble epoxide hydrolase (sEH). The results showed that acteoside is the most potent inhibitor of sEH, with an IC of 33.5 ± 0.5 μM. Additional active components, including harpagide, tryptophan, and 8-acetate-harpagide, along with acteoside, were tentatively identified using high-performance liquid chromatography photodiode array tandem mass spectrometry (HPLC-PDA-MS/MS) and quantified using an ultraviolet detector at 210 nm. Further, an ultrasonic-assisted extraction technique for extraction of four bioactive compounds in SSM was developed and optimized using response surface methodology (RSM). The optimal extraction conditions were: extraction time, 30.46 minutes; extraction temperature, 67.95 °C, and methanol concentration 53.85%. The prediction model of RSM was validated with laboratory experiments. The similarity between predicted and actual values was 97.84%. The extraction method is thus a rapid, environment-friendly, energy-saving method can be applied to extract bioactive components from SSM in large quantities.
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http://dx.doi.org/10.1080/10826068.2020.1821217DOI Listing
September 2020

[Epidemiological analysis of liver injury related to bone diseases].

Zhongguo Zhong Yao Za Zhi 2020 Aug;45(16):3974-3980

Department of Pharmacology, Xuanwu Hospital of Capital Medical University Beijing 100053, China.

A total of 1 392 reports on liver injury associated adverse drug reaction(LI-ADR) related to bone diseases were retrospectively analyzed based on national ADR monitoring system [18.75% of the patients used traditional Chinese medicine(TCM) alone and 68.68% used Western medicine alone]. This kind of cases accounted for 2.5% of all drug-related liver injury adverse reactions, ranking top ten of all drug categories. The number of reported cases and the proportion of serious cases showed an increasing trend from 2012 to 2016. The average age of the patients was(54.2±15.8) years old, and there was little difference in overall gender(male-female 1.04∶1). However, the number of female patients with rheumatoid arthritis was significantly higher than that of male patients(male-female 1∶2.6), while the number of male patients with gout was significantly higher than that of female patients(male-female 7.16∶1). The overall prognosis was good, with the recovery and improvement rate of 85.27%. The time from medication to liver injury varied due to different medicines. The median time to liver injury was 27 days in TCM alone group, later than 11 days in Western me-dicine alone group(P<0.05). Drugs for bone diseases have been one of the important categories for clinical drug-induced liver injury, and the number of reported cases on liver injury caused by drugs for bone diseases is increasing, so we should pay close attention to the safe and rational use of them. The LI-ADRs of male and female were different due to their different diseases, and the latency of adverse reactions in TCM group was generally longer than that in Western medicine group. In clinical medication, liver function should be monitored according to different diseases and characteristics of drugs to prevent the risk of liver injury.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20191127.503DOI Listing
August 2020

Polydopamine-Modified TS-1 Zeolite Framework Nanoparticles as a Matrix for the Analysis of Small Molecules by MALDI-TOF MS.

ACS Omega 2020 Aug 3;5(32):19952-19959. Epub 2020 Aug 3.

State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) using conventional organic matrices for detection of small molecules has some limitations, such as heterogeneous analyte/matrix co-crystals, as well as interference of matrices in the low-molecular-weight range. In this work, a zeolite framework nanomaterial, TS-1, was applied as a MALDI matrix for the analysis of small molecules by MALDI-MS for the first time. To improve the signal intensity and reproducibility, TS-1 was modified with polydopamine (TS-1@PDA). Using TS-1@PDA as a matrix, organic substances in the low-molecular-weight region such as amino acids, nucleosides, peptides, oligosaccharides, and fatty acids can be detected by MALDI-MS in positive ion mode. Compared with traditional organic matrices like 2,5-dihydroxybenzoic acid (2,5-DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), TS-1@PDA has the advantages including the formation of uniform sample spots, small background interference at low molecular weight, and better salt tolerance. Furthermore, this matrix was employed for the analysis of endogenous glucose in urine samples, and the level of glucose was quantified with a linear range of 0-10 mM ( > 0.98). The results demonstrated that TS-1@PDA has the potential to be used as an effective MALDI matrix for the analysis of small molecules in biological samples with excellent reproducibility and moderate sensitivity.
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http://dx.doi.org/10.1021/acsomega.0c00992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439277PMC
August 2020

Enhancement of an In Vivo Anti-Inflammatory Activity of Oleanolic Acid through Glycosylation Occurring Naturally in .

Molecules 2020 Aug 13;25(16). Epub 2020 Aug 13.

College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.

(Lardizabalaceae) has been used as a traditional herbal medicine in Korea and China for its anti-inflammatory and analgesic properties. As part of a bioprospecting program aimed at the discovery of new bioactive compounds from Korean medicinal plants, a phytochemical study of leaves was carried out leading to isolation of two oleanane-type triterpene saponins, 3--[-d-glucopyranosyl (1→2)--l-arabinopyranosyl] oleanolic acid-28--[-d-glucopyranosyl (1→6)--d-glucopyranosyl] ester () and 3---l-arabinopyranosyl oleanolic acid-28--[-d-glucopyranosyl (1→6)--d-glucopyranosyl] ester (). Their structures were established unambiguously by spectroscopic methods such as one- and two-dimensional nuclear magnetic resonance and infrared spectroscopies, high-resolution electrospray ionization mass spectrometry and chemical reactions. Their anti-inflammatory activities were examined for the first time with an animal model for the macrophage-mediated inflammatory response as well as a cell-based assay using an established macrophage cell line (RAW 264.7) in vitro. Together, it was concluded that the saponin constituents, when they were orally administered, exerted much more potent activities in vivo than their sapogenin core even though both the saponins and the sapogenin molecule inhibited the RAW 264.7 cell activation comparably well in vitro. These results imply that saponins from leaves have a definite advantage in the development of oral medications for the control of inflammatory responses.
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http://dx.doi.org/10.3390/molecules25163699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464308PMC
August 2020

Ultrathin interfacial modification of Li-rich layered oxide electrode/sulfide solid electrolyte via atomic layer deposition for high electrochemical performance batteries.

Nanotechnology 2020 Nov 28;31(45):454001. Epub 2020 Jul 28.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, People's Republic of China.

Herein, Li-rich layered oxides (LLOs) are modified by sulfide solid electrolyte LiGePS (LGPS) with high ionic conductivity to enhance the diffusion of Li and an ultrathin AlO layer is interposed between LLOs and LGPS through the atomic layer deposition (ALD) technique to inhibit the development of the highly resistive space-charge layer, the side reactions and structure transition of the composites, thus excellently promoting the electrochemical properties of the composites in liquid electrolyte. Among the different ALD cycles of AlO, 10 cycles of ultrathin AlO layer achieves the greatest electrochemical performance. The beginning discharge capacity of LLOs@AlO/LGPS composites comes up to 233.4 mA h g with a capacity retention of 90.6% and a voltage retention of 97.3% after 100 cycles at 0.2 C. The composites also exhibit the optimal rate capability and a high energy density of 581 Wh kg at 1 C. The galvanostatic intermittent titration technique test indicates that the composites (LLOs@AlO/LGPS) possess the greatest Li diffusion coefficient (1.58 × 10 cm s) compared to LLOs (0.85 × 10 cm s) and LLOs/LGPS (1.10 × 10 cm s). More importantly, charge curves at the beginning of the initial charge and electrochemical impedance spectroscopy curves clearly reveal the inhibition of the development of the highly resistive space-charge layer.
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http://dx.doi.org/10.1088/1361-6528/abaa12DOI Listing
November 2020

New-onset non-convulsive status epilepticus in an adult with hemophagocytic lymphohistiocytosis: a case report.

Quant Imaging Med Surg 2020 Jul;10(7):1559-1565

Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.21037/qims-19-360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358409PMC
July 2020

Highly Selective Oxidation of Organic Sulfides by a Conjugated Polymer as the Photosensitizer for Singlet Oxygen Generation.

ACS Appl Mater Interfaces 2020 Aug 22;12(31):35475-35481. Epub 2020 Jul 22.

Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.

A cationic conjugated polyelectrolyte PPET3-N2 was used as a photosensitizer for photocatalytic oxidation of organic sulfides, including thioanisole, ethyl phenyl sulfide, 4-methylphenyl methyl sulfide, etc., to form sulfoxides with good yields and high selectivity. Oxidation reactions were performed in both batch and microfluidic reactors, where the microfluidic reactor can significantly promote the conversion of photocatalytic oxidation reaction to over 98% in about 8 min. Further studies of the photocatalytic oxidation of the antitumor drug ricobendazole in the microfluidic reactor demonstrate the potential application of the polymer material in organic reactions given its high selectivity, good efficiency, and operation convenience.
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http://dx.doi.org/10.1021/acsami.0c10162DOI Listing
August 2020

Prognostic and Clinicopathological Significance of Long Noncoding RNA GHET1 in Human Solid Tumors: a Meta-Analysis.

Clin Lab 2020 Jul;66(7)

Background: Gastric carcinoma high expressed transcript 1 (GHET1) is a long noncoding RNA (lncRNA) that is aberrantly upregulated in numerous cancers. Here we carried out a systematical meta-analysis to investigate the potential prognostic and clinicopathologic significance of lncRNA GHET1 expression in multiple types of malignant tumors.

Methods: A systematic document retrieval of the online databases Embase, PubMed, and CNKI for studies relevant to the connection between lncRNA GHET1 level and clinical result of tumors was conducted (up to May 8, 2019). The aggregated odds rates (ORs)/hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship.

Results: Nine hundred twenty carcinoma patients were enrolled from 12 studies in the present study. The results revealed that increased GHET1 expression was obviously related to worse overall survival (OS) (pooled HR = 2.75, 95% CI: 2.18 - 3.45, p < 0.001). Subgroup analysis results indicated that high GHET1 levels present a stronger connection with poor OS in digestive system cancers. In addition, cancer patients with high GHET1 levels are likely to have distant metastasis (DM) (OR = 12.5, 95% CI: 2.31 - 66.67, p = 0.003), lymph node metastasis (LNM) (OR = 4.29, 95% CI: 2.930 - 6.29, p < 0.001), and advanced clinical staging OR = 4.6, 95% CI: 3.33 - 6.34, p < 0.001), but GHET1 expression was not correlated with gender (p = 0.586), age (p = 0.332), tumor differentiation (p = 0.550), or tumor size (p = 0.084).

Conclusions: Overexpression of GHET1 may be a convincing adverse prognostic factor that contributes to the clinical decision-making procedure of cancer treatment.
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http://dx.doi.org/10.7754/Clin.Lab.2019.191102DOI Listing
July 2020

Adaptation to Extreme Antarctic Environments Revealed by the Genome of a Sea Ice Green Alga.

Curr Biol 2020 Sep 2;30(17):3330-3341.e7. Epub 2020 Jul 2.

First Institute of Oceanography, Ministry of Natural Resources, 266061 Qingdao, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, 266237 Qingdao, China. Electronic address:

The unicellular green alga Chlamydomonas sp. ICE-L thrives in polar sea ice, where it tolerates extreme low temperatures, high salinity, and broad seasonal fluctuations in light conditions. Despite the high interest in biotechnological uses of this species, little is known about the adaptations that allow it to thrive in this harsh and complex environment. Here, we assembled a high-quality genome sequence of ∼542 Mb and found that retrotransposon proliferation contributed to the relatively large genome size of ICE-L when compared to other chlorophytes. Genomic features that may support the extremophilic lifestyle of this sea ice alga include massively expanded gene families involved in unsaturated fatty acid biosynthesis, DNA repair, photoprotection, ionic homeostasis, osmotic homeostasis, and reactive oxygen species detoxification. The acquisition of multiple ice binding proteins through putative horizontal gene transfer likely contributed to the origin of the psychrophilic lifestyle in ICE-L. Additional innovations include the significant upregulation under abiotic stress of several expanded ICE-L gene families, likely reflecting adaptive changes among diverse metabolic processes. Our analyses of the genome, transcriptome, and functional assays advance general understanding of the Antarctic green algae and offer potential explanations for how green plants adapt to extreme environments.
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http://dx.doi.org/10.1016/j.cub.2020.06.029DOI Listing
September 2020

A quantitative LC-MS/MS method for analysis of mitochondrial -specific oxysterol metabolism.

Redox Biol 2020 09 1;36:101595. Epub 2020 Jun 1.

Department of Nutrition, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. Electronic address:

Oxysterols are critical regulators of inflammation and cholesterol metabolism in cells. They are oxidation products of cholesterol and may be differentially metabolised in subcellular compartments and in biological fluids. New analytical methods are needed to improve our understanding of oxysterol trafficking and the molecular interplay between the cellular compartments required to maintain cholesterol/oxysterol homeostasis. Here we describe a method for isolation of oxysterols using solid phase extraction and quantification by liquid chromatography-mass spectrometry, applied to tissue, cells and mitochondria. We analysed five monohydroxysterols; 24(S)-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, 7 ketocholesterol and three dihydroxysterols 7α-24(S)dihydroxycholesterol, 7α-25dihydroxycholesterol, 7α-27dihydroxycholesterol by LC-MS/MS following reverse phase chromatography. Our new method, using Triton and DMSO extraction, shows improved extraction efficiency and recovery of oxysterols from cellular matrix. We validated our method by reproducibly measuring oxysterols in mouse brain tissue and showed that mice fed a high fat diet had significantly lower levels of 24S/25diOHC, 27diOHC and 7ketoOHC. We measured oxysterols in mitochondria from peripheral blood mononuclear cells and highlight the importance of rapid cell isolation to minimise effects of handling and storage conditions on oxysterol composition in clinical samples. In addition, in vitro cell culture systems, of THP-1 monocytes and neuronal-like SH-SH5Y cells, showed mitochondrial-specific oxysterol metabolism and profiles were lineage specific. In summary, we describe a robust and reproducible method validated for improved recovery, quantitative linearity and detection, reproducibility and selectivity for cellular oxysterol analysis. This method enables subcellular oxysterol metabolism to be monitored and is versatile in its application to various biological and clinical samples.
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http://dx.doi.org/10.1016/j.redox.2020.101595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317222PMC
September 2020

Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology.

J Ethnopharmacol 2020 Oct 10;261:113078. Epub 2020 Jun 10.

Department of China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, 100039, China. Electronic address:

Ethnopharmacological Relevance: Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed.

Materials And Methods: The "compound-target-cell-disease" network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model.

Results: Through the "compound-target-cell-disease" network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3'-O-gallate, torachrysone-8-O-beta-D-(6'-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB.

Conclusions: This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism.
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http://dx.doi.org/10.1016/j.jep.2020.113078DOI Listing
October 2020

Genome sequence of Kobresia littledalei, the first chromosome-level genome in the family Cyperaceae.

Sci Data 2020 06 11;7(1):175. Epub 2020 Jun 11.

State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, 850000, China.

Kobresia plants are important forage resources in the Qinghai-Tibet Plateau and are essential in maintaining the ecological balance of grasslands. Therefore, it is beneficial to obtain Kobresia genome resources and study the adaptive characteristics of Kobresia plants in the Qinghai-Tibetan Plateau. We assembled the genome of Kobresia littledalei C. B. Clarke, which was about 373.85 Mb in size. 96.82% of the bases were attached to 29 pseudo-chromosomes, combining PacBio, Illumina and Hi-C sequencing data. Additional investigation of the annotation identified 23,136 protein-coding genes. 98.95% of these were functionally annotated. According to phylogenetic analysis, K. littledalei in Cyperaceae separated from Poaceae about 97.6 million years ago after separating from Ananas comosus in Bromeliaceae about 114.3mya. For K. littledalei, we identified a high-quality genome at the chromosome level. This is the first time a reference genome has been established for a species of Cyperaceae. This genome will help additional studies focusing on the processes of plant adaptation to environments with high altitude and cold weather.
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http://dx.doi.org/10.1038/s41597-020-0518-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289886PMC
June 2020

Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

Front Pharmacol 2020 25;11:746. Epub 2020 May 25.

Department of China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.

As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by gene expression and enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.
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http://dx.doi.org/10.3389/fphar.2020.00746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261828PMC
May 2020

Soluble epoxide hydrolase inhibitors from (Wall.) Decne.

Nat Prod Res 2020 Jun 8:1-6. Epub 2020 Jun 8.

Institute of Natural Products Chemistry (INPC), Vietnam Academy of Science and Technology (VAST), Caugiay, Hanoi, Vietnam.

Nine bioactive compounds, including one new dihydroisocoumarin glycoside, 3-thunberginol C 6---D-glucopyranoside (), were isolated by chromatographic separation from the fruits of the Vietnamese medicinal plant (Wall.) Decne. 3-thunberginol C 6---D-glucopyranoside was determined as a mixture of boat-like conformers based on NMR evidence and density functional theory (DFT) calculations. The inhibition of soluble epoxide hydrolase (sEH) by the isolated compounds was comparable to that of AUDA (positive control), yielding IC values ranging from 10.0 ± 0.6 to 88.4 ± 0.2 µM. Among isolated compounds, 3-methoxy-4-hydroxy-benzoic acid () and 2',6'-dihydroxy 3',4'-dimethoxychalcone () were identified as a potent inhibitor of sEH, with IC values of 19.3 ± 2.2 and 10.0 ± 0.6 mM, respectively. These results suggest that the fruits of may be useful as daily supplements for the prevention of cardiovascular and other sEH-related diseases.[Formula: see text].
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http://dx.doi.org/10.1080/14786419.2020.1774759DOI Listing
June 2020

Linc02349 promotes osteogenesis of human umbilical cord-derived stem cells by acting as a competing endogenous RNA for miR-25-3p and miR-33b-5p.

Cell Prolif 2020 May 29;53(5):e12814. Epub 2020 Apr 29.

Institute of Bioadditive Manufacturing, Jiangxi University of Science and Technology, Nanchang, China.

Objectives: Increasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation.

Materials And Methods: Human umbilical cord-derived stem cells (hUC-MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral-mediated gene delivery method. Bioinformatics prediction, Ago2-RIP assay and dual-luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349-regulated genes, miR-25-3p and miR-33b-5p, were explored by ChIP, RIP and Western blotting assays. Micro-CT was used to measure the osteogenic content in bone formation assay in vivo.

Results: Linc02349 overexpression improves osteogenic differentiation by in vitro and in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR-25-3p and miR-33b-5p to control expression abundance of SMAD5 and Wnt10b, respectively, which eventually activated Dlx5/OSX pathway and hence promoted osteogenic differentiation. In addition, we revealed that STAT3 interacts with linc02349 promoter region and positively regulates the linc02349 transcriptional activity.

Conclusion: These findings identify that linc02349 modulates the osteogenic differentiation through acting as a sponge RNA of miR-25-3p and miR-33b-5p and regulating SMAD5 and Wnt10b, and proposed a new interaction between STAT3 and linc02349, which could be a potential target in the process the osteogenesis of hUC-MSCs for future clinical application.
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http://dx.doi.org/10.1111/cpr.12814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260076PMC
May 2020