Publications by authors named "Lijun Zhu"

254 Publications

Downregulation of Arntl mRNA Expression in Women with Hypertension: A Case-Control Study.

Kidney Blood Press Res 2021 Sep 3:1-8. Epub 2021 Sep 3.

Department of Epidemiology, School of Public Health, and Institute of Chronic Disease Prevention and Control, Wannan Medical College, Wuhu, China.

Background: Previous studies have reported that disturbance of endogenous circadian rhythms enhances the chance of hypertension and suggested that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was aimed to investigate the association of the mRNA expression of aryl hydrocarbon receptor nuclear translocator like (Arntl), clock circadian regulator (Clock), and period circadian regulators 1 and 2 (Per1 and Per2) with hypertension and blood pressure levels.

Methods: A total of 172 subjects were recruited in this study, including 86 hypertension and 86 nonhypertension controls. The mRNA expression levels in peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction. The differences in Arntl, Clock, Per1, and Per2 mRNA expression were compared between the 2 groups, and the relationship between mRNA expression and cardiometabolic risk profiles was also assessed.

Results: We found that the mRNA expression of Arntl was downregulated in the hypertension cases compared with controls in women (1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06], p = 0.031). There was a significant negative correlation between the Arntl mRNA expression and SBP (r = -0.301, p = 0.004) and DBP (r = -0.222, p = 0.034) in women. In men, a negative correlation between the Per1 mRNA expression and SBP (r = -0.247, p = 0.026) was found.

Conclusions: The Arntl mRNA expression may play an important role in progression of hypertension in women.
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http://dx.doi.org/10.1159/000518669DOI Listing
September 2021

Serum nitrite and nitrate: A potential biomarker for post-covid-19 complications?

Free Radic Biol Med 2021 Aug 30;175:216-225. Epub 2021 Aug 30.

School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, China. Electronic address:

Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NO), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NO had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NO is unknown. In this study, serum NO and NO were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO and NO/NO than the uninfected group (p < 0.0001), with significantly higher NO levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO, low NO/NO and high NO may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.08.237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404395PMC
August 2021

[Application of organic fluorescent probe-assisted near infrared fluorescence imaging in cervical cancer diagnosis].

Sheng Wu Gong Cheng Xue Bao 2021 Aug;37(8):2678-2687

School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, Xinjiang, China.

Fluorescence imaging has been widely used in the fields of biomedicine and clinical diagnosis. Compared with traditional fluorescence imaging in the visible spectral region (400-760 nm), near-infrared (NIR, 700-1 700 nm) fluorescence imaging is more helpful to improve the signal-to-noise ratio and the sensitivity of imaging. Highly-sensitive fluorescent probes are required for high-quality fluorescence imaging, and the rapid development of nanotechnology has led to the emergence of organic dyes with excellent fluorescent properties. Among them, organic fluorescent probes with the advantages of high safety, good biocompatibility, and high optical stability, are more favorable than inorganic fluorescent probes. Therefore, NIR fluorescence imaging assisted with organic fluorescent probes can provide more structural and dynamic information of biological samples to the researchers, which becomes a hot spot in the interdisciplinary research field of optics, chemistry and biomedicine. This review summarizes the application of NIR organic fluorescent probes in cervical cancer imaging. Several typical organic fluorescent probes (such as indocyanine green, heptamethine cyanine dye, rhodamine and polymer fluorescent nanoparticles) assisted NIR fluorescence imaging and their applications in cervical cancer diagnosis were introduced, and the future development and application of these techniques were discussed.
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http://dx.doi.org/10.13345/j.cjb.200608DOI Listing
August 2021

Higher Levels of C-Reactive Protein in the acute phase of stroke Indicate an Increased Risk for Post-stroke Depression: A Systematic Review and Meta-Analysis.

Neurosci Biobehav Rev 2021 Aug 17. Epub 2021 Aug 17.

Department of Neurology, Neuroscience Centre, the First Teaching Hospital of Jilin University, Changchun, China. Electronic address:

Background: Investigations have revealed the association between inflammation and post-stroke depression (PSD). However, whether the C-reactive protein (CRP) level, a biomarker of inflammation, would affect the development of PSD is still controversial.

Methods: A systematic search of databases was performed for eligible studies. Standardized Mean Difference (SMD) with 95% Confidence Interval (CI) was used to assess the association between the CRP level in the acute phase of stroke and the risk of PSD.

Results: 13 cohort studies that involved 3536 participants were included. Combined results showed that compared with non-PSD patients, the CRP level of PSD patients was significantly higher on admission (SMD = 0.19, 95% CI: 0.12-0.27). A subgroup analysis by classifying the assessment time of depression showed obvious differences of the CRP levels between the PSD patients who were diagnosed more than 1 month after stroke and the non-PSD (1-3 months: SMD = 0.16, 95% CI: 0.06-0.25; >3months: SMD = 0.34, 95% CI: 0.18-0.51).

Conclusion: A higher level of CRP in the acute phase of stroke suggests an increased risk for PSD.
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http://dx.doi.org/10.1016/j.neubiorev.2021.08.018DOI Listing
August 2021

Near-infrared emissive polymer-coated IR-820 nanoparticles assisted photothermal therapy for cervical cancer cells.

J Biophotonics 2021 Jul 31:e202100117. Epub 2021 Jul 31.

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, China.

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel [email protected] nanoparticles (NPs). Then, the optical and thermal properties of [email protected] NPs were studied in detail. The [email protected] NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the [email protected] NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The [email protected] NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.
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http://dx.doi.org/10.1002/jbio.202100117DOI Listing
July 2021

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer.

Int J Nanomedicine 2021 17;16:4847-4861. Epub 2021 Jul 17.

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, People's Republic of China.

Purpose: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the [email protected] theranostic nanoplatform.

Methods: In this study, ICG-loaded BSA nanoparticles (NPs) and the [email protected] NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of [email protected] NPs under 808 nm laser irradiation.

Results: The [email protected] NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the [email protected] NPs to form the [email protected] theranostic nanoplatform. The [email protected] NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the [email protected] NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice.

Conclusion: To improve the anti-tumor efficiency of the [email protected] NPs, the chemotherapeutic drug DOX was loaded into the [email protected] NPs. The NIR excitation/emission and targeted [email protected] NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.
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http://dx.doi.org/10.2147/IJN.S318678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297555PMC
July 2021

The immediate and subsequent effects of public health interventions for COVID-19 on the leisure and recreation industry.

Tour Manag 2021 Dec 13;87:104393. Epub 2021 Jul 13.

International Center for Recreation and Tourism Research, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China.

Public health interventions to combat COVID-19 can be viewed as an exogenous shock to the economy, especially for industries-such as leisure, recreation, and tourism-that rely heavily on human mobility. This study investigates whether and how exactly the economic impact of government public health policies varies over time. Focusing on the leisure and recreation industry, we use data for 131 countries/regions from February to May 2020 and employ generalized difference-in-differences models to investigate the short- and longer-term effects of public health policies. We find that stricter policies lead, on average, to an immediate 9.2-percentage-point drop in leisure and recreation participation. Even so, that industry recovers in about seven weeks after a COVID-19 outbreak in countries/regions that undertake active interventions. After thirteen weeks, leisure and recreation involvement recovers to 70% of pre-pandemic levels in a place that actively intervened but stagnates at about 40% in one that did not.
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http://dx.doi.org/10.1016/j.tourman.2021.104393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275490PMC
December 2021

Changes in weight and height among Chinese preschool children during COVID-19 school closures.

Int J Obes (Lond) 2021 Jul 15. Epub 2021 Jul 15.

Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China.

Background And Objectives: COVID-19-related school closures may increase the prevalence of childhood obesity, which has aroused public concerns. We aimed to analyze the weight and height changes in Chinese preschool children during the COVID-19-related school closures period.

Methods: A total of 124,603 children from multi-city kindergartens in China were included in this study. We evaluated the prevalence of overweight and obese in preschool children experienced school closures, and compared the changes in BMI, weight, and height of preschool children among COVID-19 school closures period, the same period last year and the same period the year before last.

Results: After the school closures, childhood obesity prevalence increased, whereas overweight prevalence decreased. During school closures, the average increase in height was about 1 cm less as compared with the same period last year and the year before last, but no noteworthy difference in the weight change was observed among the three periods.

Conclusions: During COVID-19 school closures, children's height increase seemed to be more affected than weight change. Innovative, robust, and highly adaptable strategies should be taken to increase physical activity, reduce sedentary time and promote healthy diets, to minimize the adverse impact of school closures.
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http://dx.doi.org/10.1038/s41366-021-00912-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281806PMC
July 2021

Novel amorphous solid dispersion based on natural deep eutectic solvent for enhancing delivery of anti-tumor RA-XII by oral administration in rats.

Eur J Pharm Sci 2021 Nov 10;166:105931. Epub 2021 Jul 10.

Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

At present, oral chemotherapy showing the advantages of non-invasiveness, convenience, and high patient compliance, is gradually replacing traditional intravenous chemotherapy to treat patients with cancer. RA-XII, a unique natural cyclopeptide, exhibits various biological activities, such as anti-tumor, anti-angiogenic, and anti-metastatic activities. Designing an orally available formulation of RA-XII is of great importance in the development of clinically useful anticancer agents. However, RA-XII shows low oral bioavailability in rats due to its poor solubility and low permeability. To overcome these limitations, in this work, a natural deep eutectic solvent (NADES) was designed to efficiently deliver RA-XII by oral administration. A novel NADES composed of betaine and mandelic acid in the molar ratio of 1:1 (Bet-Man NADES) was successfully prepared based on a binary phase diagram of Bet and Man. Acute toxicity studies indicated that Bet-Man NADES was well tolerated with acceptable toxicity. In Bet-Man NADES solutions, the solubility of RA-XII was increased by up to 17.54-fold, and the diffusion and permeability of RA-XII carried out in a Franz cell was also significantly improved 10.35 times. In terms of biopharmaceutical classification this is translated into a change for RA-XII from class IV to class II systems. More importantly, Bet-Man NADES was transferred into the solid formulation by the inclusion of a polymer, and amorphous solid dispersions based on Bet-Man NADES (PVP K30/NADES/RA-XII, ASDs) were successfully prepared to improve uniformity, apparent solubility, dissolution, and cytotoxicity in vitro. Consequently, the oral bioavailability of RA-XII in NADES solutions and ASDs was enhanced by approximately 11.58 and 7.56 times compared with that of pure RA-XII in 0.5% CMCNa. Thus, it can be seen that a natural deep eutectic solvent and its modified amorphous solid dispersions are appropriate novel strategies for improving dissolution rate and bioavailability of poor soluble natural products such as RA-XII.
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http://dx.doi.org/10.1016/j.ejps.2021.105931DOI Listing
November 2021

Pterostilbene inhibits hepatocellular carcinoma proliferation and HBV replication by targeting ribonucleotide reductase M2 protein.

Am J Cancer Res 2021 15;11(6):2975-2989. Epub 2021 Jun 15.

Department of Pathology & Pathophysiology, and Cancer Institute of The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, China.

Hepatocellular carcinoma (HCC), one of the most deadly diseases all around the world. HBV infection is a causative factor of HCC and closely associated with HCC development. Ribonucleotide reductase (RR) is a key enzyme for cellular DNA synthesis and RR small subunit M2 (RRM2) is highly upregulated in HCC with poor survival rates. We have previously shown that HBV can activate the expression of RRM2 and the activity of RR enzyme for the viral DNA replication in host liver cells. Thus, RRM2 may be an important therapeutic target for HCC and HBV-related HCC. Pterostilbene, a natural plant component, potently inhibited RR enzyme activity with the IC of about 0.62 μM through interacting with RRM2 protein, which was much higher than current RRM2 inhibitory drugs. Pterostilbine inhibited cell proliferation with an MTT IC of about 20-40 μM in various HCC cell lines, causing DNA synthesis inhibition, cell cycle arrest at S phase, and accordingly apoptosis. On the other hand, the compound significantly inhibited HBV DNA replication in HBV genome integrated and newly transfected HCC cells, and the EC for inhibiting HBV replication was significantly lower than the IC for inhibiting HCC proliferation. Notably, pterostilbene possessed a similar inhibitory activity in sorafenib and lamivudine resistant HCC cells. Moreover, the inhibitory effects of pterostilbine against HCC proliferation and HBV replication were significantly reversed by addition of dNTP precursors, suggesting that RR was the intracellular target of the compound. Finally, pterostilbine effectively inhibited HCC xenograft growth with a relatively low toxicity in nude mouse experiments. This study demonstrates that pterostilbene is a novel potent RR inhibitor by targeting RRM2. It can simultaneously inhibit HCC proliferation and HBV replication with a potential new use for treatment of HCC and HBV-related HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263682PMC
June 2021

A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer.

Cell Death Dis 2021 07 7;12(7):683. Epub 2021 Jul 7.

Department of Pathology & Pathophysiology, and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Ribonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.
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http://dx.doi.org/10.1038/s41419-021-03969-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263627PMC
July 2021

The Association of Meteorological Factors with Cognitive Function in Older Adults.

Int J Environ Res Public Health 2021 06 2;18(11). Epub 2021 Jun 2.

School of Psychology, Shenzhen University, Shenzhen 518052, China.

Individual and meteorological factors are associated with cognitive function in older adults. However, how these two factors interact with each other to affect cognitive function in older adults is still unclear. We used mixed effects models to assess the association of individual and meteorological factors with cognitive function among older adults. Individual data in this study were from the database of China Family Panel Studies. A total of 3448 older adults from 25 provinces were included in our analysis. Cognitive functions were measured using a memory test and a logical sequence test. We used the meteorological data in the daily climate dataset of China's surface international exchange stations, and two meteorological factors (i.e., average temperature and relative humidity) were assessed. The empty model showed significant differences in the cognitive scores of the older adults across different provinces. The results showed a main impact of residence (i.e., urban or rural) and a significant humidity-residence interaction on memory performance in older adults. Specifically, the negative association between humidity and memory performance was more pronounced in urban areas. This study suggested that meteorological factors may, in concert with individual factors, be associated with differences in memory function in older adults.
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http://dx.doi.org/10.3390/ijerph18115981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199712PMC
June 2021

Circulating ERBB3 levels are inversely associated with the risk of overweight-related hypertension: a cross-sectional study.

BMC Endocr Disord 2021 Jun 27;21(1):130. Epub 2021 Jun 27.

Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Anhui, 241002, Wuhu, China.

Background: Hypertension and overweight are independent risk factors for cardiovascular disease, and overweight increase the risk of developing high blood pressure. ERBB3( also known as HER3) plays a considerable role in the development of cardiovascular diseases. However, the effect of ERBB3 levels in hypertensive overweight patients is unknown. The aim of this study was to assess the association between ERBB3 levels and hypertension in overweight Chinese patients.

Methods: We evaluated the height,weight, blood pressure, biochemical indicators, and ERBB3 levels in 128 Chinese adults aged 33-79 years. Plasma ERBB3 levels were assessed by the enzyme-linked immunosorbent assay, and body mass index(BMI) was calculated as body weight divided by height squared. Participants were allocated into three groups according to blood pressure and BMI: healthy control (CNT, n = 31; normotensive and non-overweight), hypertension (HT, n = 33; hypertension and non-overweight), and hypertension with overweight (HTO, n = 64; hypertension and overweight). Statistical significance was defined as a two-tailed P < 0.05.

Results: There was no significant difference in mean ERBB3 levels among the three groups, although a linear decrease from CNT (1.13 ± 0.36), HT (1.03 ± 0.36), to HTO (0.84 ± 0.26 ng/mL) was observed in men (P = 0.007). Among the drinking population, the ERBB3 level was significantly reduced in the HTO group as compared with those of the CNT and HT groups (0.76 ± 0.23 versus 1.18 ± 0.37 and 1.20 ± 0.30, respectively). ERBB3 levels were negatively correlated with diastolic blood pressure in men (r= - 0.293, P = 0.012), smoking (r= - 0.47, P = 0.004), and drinking (r = - 0.387, P = 0.008). BMI in men and among drinkers, and uric acid among drinkers were negatively correlated with ERBB3 levels. Multivariate conditional logistic regression showed that plasma ERBB3 levels were associated with a reduced risk of HTO in men [odds ratio (OR) 0.054; 95 % confidence interval (CI): 0.007-0.412) and drinkers (OR 0.002; 95 % CI: 0.000-0.101).

Conclusions: ERBB3 may contribute to the pathogenesis of hypertension in overweight patients, with BMI, gender, and drinking all potentially modulating the process.
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http://dx.doi.org/10.1186/s12902-021-00793-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237455PMC
June 2021

Age-related changes in metabolites in young donor livers and old recipient sera after liver transplantation from young to old rats.

Aging Cell 2021 07 22;20(7):e13425. Epub 2021 Jun 22.

Department of Geriatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Liver ageing not only damages liver function but also harms systemic metabolism. To better understand the mechanisms underlying liver ageing, we transplanted the livers of young rats to young and old rats and performed untargeted metabolomics to detect changes in the metabolites in the liver tissues and sera. A total of 153 metabolites in the livers and 83 metabolites in the sera were different between the old and young rats that did not undergo liver transplantation; among these metabolites, 7 different metabolites were observed in both the livers and sera. Five weeks after liver transplantation, the levels of 25 metabolites in the young donor livers were similar to those in the old rats, and this result probably occurred due to the effect of the whole-body environment of the older recipients on the young livers. The 25 altered metabolites included organic acids and derivatives, lipids and lipid-like molecules, etc. In the sera, the differences in 78 metabolites, which were significant between the young and old rats, were insignificant in the old recipient rats and made the metabolic profile of the old recipients more similar to that of the young recipients. Finally, combining the above metabolomic data with the transcriptomic data from the GEO, we found that the altered metabolites and genes in the liver were enriched in 9 metabolic pathways, including glycerophospholipid, arachidonic acid, histidine and linoleate. Thus, this study revealed important age-related metabolites and potential pathways as well as the interaction between the liver and the whole-body environment.
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http://dx.doi.org/10.1111/acel.13425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282239PMC
July 2021

Association between Serum Uric Acid and Pre-hypertension and Hypertension among Chinese Adults.

Arq Bras Cardiol 2021 06;116(6):1072-1078

Department of Epidemiology and Biostatistics, School of Public Health , Wannan Medical College / Institute of Chronic Disease Prevention and Control , Wuhu - China.

Background: Uric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase.

Objective: To evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population.

Methods: A cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant.

Results: Serum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028-2.872), 1.018 (0.627-1.654) and 1.738 (1.003-3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256-3.298).

Conclusions: This study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.
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http://dx.doi.org/10.36660/abc.20200098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288526PMC
June 2021

Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 May 3;4(5):e219807. Epub 2021 May 3.

Department of Hematology, The First Affiliated Hospital of Gannan Medical University, Jiangxi, People's Republic of China.

Importance: Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.

Objective: To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL.

Data Sources: A systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020.

Study Selection: After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantation-related mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Data Extraction And Synthesis: Data on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model.

Main Outcomes And Measures: The prespecified main outcomes were OS, PFS, and TRM.

Results: Of 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this meta-analysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed.

Conclusions And Relevance: In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.9807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160596PMC
May 2021

Serum/Plasma Zinc Is Apparently Increased in Ischemic Stroke: a Meta-analysis.

Biol Trace Elem Res 2021 Apr 6. Epub 2021 Apr 6.

Department of Epidemiology and Biostatistics, School of Public Health, Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, China.

Zinc (Zn) is found in many neuronal pathways in the brain and has implications for neuromodulation and cerebrovascular disease. However, the association between Zn levels and stroke risk remains controversial. Therefore, we conducted a meta-analysis to explore these relationships. A systematic literature search using PubMed, EMBASE database, and Google Scholar was performed for relevant articles from inception to August 2020. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were considered the effect sizes and statistical analyses were performed using Stata 12.0. A total of 12 studies involving 1878 cases of stroke and 1754 controls were enrolled. Overall, the meta-analysis demonstrated no significant difference in Zn levels between the stroke group and control group (SMD =-0.18, 95% CI =-0.69 to 0.32, P = 0.480). Subgroup analysis showed that type of stroke had an influence on the Zn levels. A meta-analysis of nine ischemic stroke (IS) studies, which included 1645 cases and 1585 controls, revealed that the Zn levels were significantly higher in IS patients than in controls (SMD (95% CI): 0.61(0.04, 1.19), P = 0.036), but no significant association was found between Zn levels and risk of hemorrhagic stroke (P = 0.113). Egger's test indicated no significant publication bias. This meta-analysis indicates that higher Zn levels may be associated with increased risk of IS; however, these findings should be further confirmed.
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http://dx.doi.org/10.1007/s12011-021-02703-4DOI Listing
April 2021

Preparative separation of five polyphenols from the fruits of Sorbus pohuashanensis Hedl. by high-speed counter-current chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 5;1172:122620. Epub 2021 Mar 5.

School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036, PR China; Natural Products Pharmaceutical Engineering Technology Research Center of Liaoning Province, Shenyang 110036, PR China. Electronic address:

The fruits of Sorbus pohuashanensis Hedl. (S. pohuashanensis) are rich in polyphenols with many beneficial effects such as anti-inflammatory, anti-tussive, anti-asthmatic and anti-cancer. In this study, five polyphenols, including three phenolic acids and two flavonoids, were successfully prepared from the fruits of S. pohuashanensis by high-speed counter-current chromatography (HSCCC) using different solvent systems for the first time. Ethyl acetate-n-butanol-water (3.5:1.5:5, v/v) was screened as the two-phase system to separate neochlorogenic acid (1), chlorogenic acid (2), quercetin 3-O-(6″-α-L-rhamnopyranosyl-4'″-α-L-rhamnopyranosyl)-β-D-glucopyranoside (3) and rutin (5). N-hexane-ethyl acetate-methanol-water (1:3:1:3.5, v/v) was first utilized to isolate 3,5-O-dicaffeoylquinic acid (4). The purities of all these compounds were above 95%. In addition, their chemical structures were identified by mass spectrometer (MS), nuclear magnetic resonance (NMR) or the standards. These results indicated that HSCCC was an effective method to separate polyphenols compounds from the fruits of S. pohuashanensis.
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http://dx.doi.org/10.1016/j.jchromb.2021.122620DOI Listing
May 2021

Fully Spin-Transparent Magnetic Interfaces Enabled by the Insertion of a Thin Paramagnetic NiO Layer.

Phys Rev Lett 2021 Mar;126(10):107204

Cornell University, Ithaca, New York 14850, USA.

Spin backflow and spin-memory loss have been well established to considerably lower the interfacial spin transmissivity of metallic magnetic interfaces and thus the energy efficiency of spin-orbit torque technologies. Here, we report that spin backflow and spin-memory loss at Pt-based heavy metal-ferromagnet interfaces can be effectively eliminated by inserting an insulating paramagnetic NiO layer of optimum thickness. The latter enables the thermal magnon-mediated essentially unity spin-current transmission at room temperature due to considerably enhanced effective spin-mixing conductance of the interface. As a result, we obtain dampinglike spin-orbit torque efficiency per unit current density of up to 0.8 as detected by the standard technology ferromagnet FeCoB and others, which reaches the expected upper-limit spin Hall ratio of Pt. We establish that Pt/NiO and Pt-Hf/NiO are two energy-efficient, integration-friendly, and high-endurance spin-current generators that provide >100 times greater energy efficiency than sputter-deposited topological insulators BiSb and BiSe. Our finding will benefit spin-orbitronic research and advance spin-torque technologies.
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http://dx.doi.org/10.1103/PhysRevLett.126.107204DOI Listing
March 2021

Changes of Opioid Consumption After Lumbar Fusion Using Ultrasound-Guided Lumbar Erector Spinae Plane Block: A Randomized Controlled Trial.

Pain Physician 2021 03;24(2):E161-E168

Department of Anesthesiology, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China.

Background: The erector spinae plane block (ESPB) is gaining popularity in lumbar fusion for postoperative pain management.

Objectives: The aim of this study was to investigate the changes of opioid consumption after surgery, the range of cold temperature sensory blockade, pain, and safety.

Study Design: Randomized controlled study.

Setting: Single center.

Methods: Patients who were randomized to ESPB with 0.375% ropivacaine (ropivacaine group) and mock ESPB with saline (saline group) and underwent posterior lumbar fusion surgery. The primary endpoint was the total dosage of oxycodone. Secondary endpoints included remifentanil consumption, postoperative pain scores, postoperative adverse events, safety, and range of cold hypoesthesia.

Results: Oxycodone consumption in the first 48 hours after surgery was significantly lower in the ropivacaine group than in the saline group (P < 0.05). Remifentanil consumption was significantly lower in the ropivacaine group compared with the saline group during the surgery (0.69 ± 0.03 mg vs. 0.85 ± 0.04 mg, P < 0.05). The areas of cold hypoesthesia were identified in the ropivacaine group after the block, but not in the saline group. Rest and exercise pain scores after surgery were significantly lower in the ropivacaine group than in the saline group (P < 0.05). The overall safety of the ropivacaine group were generally comparable to that of the saline group.

Limitations: The areas of cold hypoesthesia were tested at different time points after ESPB, but the area of sensory loss was not tested, and the recovery of postoperative sensation was not recorded. In addition, we tested only temperature sensation, but not acupuncture pain.

Conclusions: Ultrasound-guided lumbar ESPB reduces the amount of analgesics required during and after lumbar fusion and reduces the postoperative Visual Analog Scale pain score.
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March 2021

Spontaneous Folding Growth of Graphene on h-BN.

Nano Lett 2021 03 23;21(5):2033-2039. Epub 2021 Feb 23.

International Center for Quantum Design of Functional Materials, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Strongly Coupled Quantum Matter Physics, Department of Physics, and Synergetic Innovation Center of Quantum Information & Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

Graphene has been the subject of much research, with structural engineering frequently used to harness its various properties. In particular, the concepts of graphene origami and kirigami have inspired the design of quasi-three-dimensional graphene structures, which possess intriguing mechanical, electronic, and optical properties. However, accurate controlling the folding process remains a big challenge. Here, we report the discovery of spontaneous folding growth of graphene on the h-BN substrate via adopting a simple chemical vapor deposition method. Folded edges are formed when two stacked graphene layers share a joint edge at a growth temperature up to 1300 °C. Using first-principles density functional theory calculations, the bilayer graphene with folded edges is demonstrated to be more stable than that with open edges. Utilizing this novel growth mode, hexagram bilayer graphene containing entirely sealed edges is eventually realized. Our findings provide a route for designing graphene devices with a new folding dimension.
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http://dx.doi.org/10.1021/acs.nanolett.0c04596DOI Listing
March 2021

The association of eating behaviors with blood pressure levels in college students: a cross-sectional study.

Ann Transl Med 2021 Jan;9(2):155

Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

Backgrounds: The present study aimed to investigate the relationship between eating habits and blood pressure levels in college students in order to provide more insights into the prevention and control of hypertension.

Methods: A self-administered questionnaire was distributed to first-year college students. The demographic characteristics, eating behaviors, smoking and drinking status, and physical activity of 3,324 eligible respondents were analyzed. Multivariate logistics regression model was used to analyze the association of eating behaviors with blood pressure levels.

Results: The study participants had a mean (SD) age of 18.51 (1.00) years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were 114.08 and 70.92 mmHg, respectively. The overall prevalence of hypertension was 7.2%; and the prevalence among males and females was 12.9% and 3.2%, respectively. Multivariate logistic regression results confirmed that students' taste preference, desserts, and late-night snacks were associated with hypertension. Students who ate spicy food had a lower risk of high blood pressure (OR =0.642, P=0.028); as was having dessert 3-6 times a week (OR =0.702, P=0.037), while those who ate late-night snacks on 6-7 days of the week had a higher risk for hypertension (OR =2.093, P=0.013).

Conclusions: More targeted interventions should be taken to improve students' eating habits and control their blood pressure.
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http://dx.doi.org/10.21037/atm-20-8031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867881PMC
January 2021

Design, synthesis, and anti-tumor activities of novel Brevinin-1BYa peptidomimetics.

Bioorg Med Chem Lett 2021 04 5;37:127831. Epub 2021 Feb 5.

Luodian Clinical Drug Research Center, Institute for Translational Medicine Research, Shanghai University, Shanghai, China. Electronic address:

Brevinin-1BYa is an amphibian skin-derived peptide that exhibits promising anti-microbial activity against gram-positive and -negative bacteria. However, the anti-tumor activity of Brevinin-1BYa remains unclear, and, more importantly, its therapeutic application is limited owing to its poor protease and reduction stability. In this study, a series of novel Brevinin-1BYa derivatives, including O-linked N-acetyl-glucosamine glyclopeptides and disulfide bond mimetics, were designed and synthesized. Additionally, their anti-tumor activity against human prostate cancer cell line C4-2B, human NSCLC cell line A549 (adenocarcinoma), and human hepatoma cells line HuH-7 was investigated. Among these, the thioether bridge substituted peptidomimetic Brevinin-1BYa-3 displayed improved reduction stability, more stable secondary structure, greater protease stability, and increased anti-tumor activity compared with the original peptide, rendering it a promising leading compound for drug development, particularly for applications against malignant tumors.
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http://dx.doi.org/10.1016/j.bmcl.2021.127831DOI Listing
April 2021

Spatial-temporal distribution of sediment phosphorus with sediment transport in the Three Gorges Reservoir.

Sci Total Environ 2021 May 9;769:144986. Epub 2021 Jan 9.

State Key Laboratory of Hydrology, Water Resources and Hydraulic Engineering, Nanjing Hydraulic Research Institute, Nanjing 210029, China.

Suspended sediment is an important phosphorus (P) adsorption medium in river catchments. Early adsorption isotherm models often ignored sediment heterogeneity, resulting in incorrect sediment P estimates in field environments. In the Three Gorges Reservoir (TGR), China, P load assessment is essential to eutrophication risk management, but the sediment P evolution in the TGR is unclear. Herein, the P-adsorption capacity of suspended sediment was estimated with an improved Langmuir model via sediment parameter consideration, and the long-term distribution and variations in simulated sediment P with sediment transport were assessed from 2003- 2016. The results showed that the improved Langmuir model attained a good fit with experimental and field data. The sediment load entering the TGR significantly decreased, especially the median size (D) fraction smaller than 0.008 mm, resulting in long-term discharged sediment load decline and annual mean D increase. Meanwhile, the annual sediment P load in the TGR decreased from 7.46- 22.38 kg/s in 2003 to 1.74- 4.73 kg/s in 2016. The increasing sediment particle size reduced the sediment P load and was sensitive to the low sediment P load in the regular impoundment stage (September 2008- 2016). The flood season (June-September) transported 69.2- 98.6% of the annual sediment P. Around 62.3% of total sediment P load was retained in the TGR from 2003- 2016. The results revealed that the retention role of the Three Gorges Dam (TGD) facilitated the long-term reduction in fine sediment and sediment P in the TGR downstream. This study highlights the importance of the particle size in P-adsorption capacity estimation with suspended sediment transport.
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http://dx.doi.org/10.1016/j.scitotenv.2021.144986DOI Listing
May 2021

Identification and quantification of contributions to karst groundwater using a triple stable isotope labeling and mass balance model.

Chemosphere 2021 Jan 22;263:127946. Epub 2020 Aug 22.

Key Laboratory of Karst Georesources and Environment, Ministry of Education, Guizhou University, Guiyang, 550003, China.

Although karst groundwater systems provide critical ecosystem services in many regions worldwide, anthropogenic contamination has seriously degraded groundwater quality. Properly elucidating geochemical processes, quantifying contributions of natural and anthropogenic end members, and then protecting karst aquifer systems remain challenging from scientific and engineering aspects. To identify the hydrochemical processes and quantifying contributions of end members (especially, contamination end members), 49 samples were collected from cave waters (CW), artesian springs (AS), and gravity springs (GS) in a karst watershed in Guiyang, China. With increased anthropogenic contamination, the CW, AS, and GS characterized by a Ca-Mg-SO-HCO composition often had pH and SO concentrations exceeding USEPA secondary drinking water standards. That is attributed to the influence of water-rock interaction, rainfall, and anthropogenic sources (mainly, sewage and fertilizers), in agreement with the compositions of δS, δO, and Sr/Sr as well as the results of principal component analysis and correlation coefficients. Based on an end-member mixing model, contributions of rainfall and anthropogenic sources were 47% and 33% of GS, 52% and 41% of CW, and 58% and 35% of AS, respectively. It suggests that the karst groundwater quality is predominantly controlled by rainfall and anthropogenic sources (especially, land use). Results may be applied to properly evaluate the impacts of natural and anthropogenic sources on karst aquifers, coupled with actions to efficiently control potential contamination end members.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127946DOI Listing
January 2021

Changes and sex- and age-related differences in the expression of drug metabolizing enzymes in a KRAS-mutant mouse model of lung cancer.

PeerJ 2020 18;8:e10182. Epub 2020 Nov 18.

International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: This study aimed to systematically profile the alterations and sex- and age-related differences in the drug metabolizing enzymes (DMEs) in a KRAS-mutant mouse model of lung cancer (KRAS mice).

Methodology: In this study, the LC-MS/MS approach and a probe substrate method were used to detect the alterations in 21 isoforms of DMEs, as well as the enzymatic activities of five isoforms, respectively. Western blotting was applied to study the protein expression of four related receptors.

Results: The proteins contents of CYP2C29 and CYP3A11, were significantly downregulated in the livers of male KRAS mice at 26 weeks (3.7- and 4.4-fold, respectively,  < 0.05). SULT1A1 and SULT1D1 were upregulated by 1.8- to 7.0- fold at 20 ( = 0.015 and 0.017, respectively) and 26 weeks ( = 0.055 and 0.031, respectively). There were positive correlations between protein expression and enzyme activity for CYP2E1, UGT1A9, SULT1A1 and SULT1D1 (  ≥ 0.5, < 0.001). Western blotting analysis revealed the downregulation of AHR, FXR and PPARα protein expression in male KRAS mice at 26 weeks. For sex-related differences, CYP2E1 was male-predominant and UGT1A2 was female-predominant in the kidney. UGT1A1 and UGT1A5 expression was female-predominant, whereas UGT2B1 exhibited male-predominant expression in liver tissue. For the tissue distribution of DMEs, 21 subtypes of DMEs were all expressed in liver tissue. In the intestine, the expression levels of CYP2C29, CYP27A1, UGT1A2, 1A5, 1A6a, 1A9, 2B1, 2B5 and 2B36 were under the limitation of quantification. The subtypes of CYP7A1, 1B1, 2E1 and UGT1A1, 2A3, 2B34 were detected in kidney tissue.

Conclusions: This study, for the first time, unveils the variations and sex- and age-related differences in DMEs in C57 BL/6 (WT) mice and KRAS mice.
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http://dx.doi.org/10.7717/peerj.10182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680056PMC
November 2020

EGFR inhibitors regulate Ca concentration and apoptosis after PM exposure based on a lung-mimic microfluidic system.

Sci Total Environ 2021 Mar 11;761:143200. Epub 2020 Nov 11.

Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address:

Air pollution has side effects on human health. Epidemiology studies indicate a positive association between ambient fine particle (PM, or particles less than 2.5 μm in diameter) concentration and lung cancer. However, how fine particles affect lung cancer at the molecular level and related therapeutic methods to address these diseases are unclear. Here, the multi-omics analysis (DNA methylation and transcriptomic) was used to detect human bronchial epithelial cells (HBE), that were exposed to PM using a quantified, small, portable, and organ-level air-liquid interface microfluidic system that mimics lung functions. The results indicate that 36,838 differentially methylated genes were detected. Of these 33,796 genes were hypomethylated (beta < 0), and 2862 genes were hypermethylated (beta > 0). RNA-Seq analysis demonstrated that 19,489 genes were upregulated (logFC > 0), and 16,659 were downregulated. Furthermore, the calcium and apoptosis pathways were activated according to multi-omics analysis. The change in EGFR gene expression after PM exposure was the result of alterations of the cellular DNA methylome in the promoter. Inhibition or down-regulation of EGFR could result in the regulation of the downstream intracellular Ca concentration and apoptosis via the EGFR/PLCγ and EGFR/STAT/Bcl-XL pathways after PM exposure. EGFR inhibitors decrease the Ca concentration of cells, thereby strengthening the effects of fine particles on apoptosis. In short, the Ca concentration and the apoptosis of cells can be regulated via EGFR related pathway after PM exposure. The EGFR may be a potentially promising therapeutic target for the treatment of air pollution-induced lung cancer through regulation of the intracellular Ca concentration and apoptosis.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143200DOI Listing
March 2021

Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Mediate the Disposition of Leonurine-10-O-β-glucuronide.

Curr Drug Metab 2020 ;21(13):1060-1067

International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510006, China.

Background: Leonurine (Leo), a promising antilipemic agent that has been approved for clinical trials, is extensively metabolized into bioactive Leonurine-10-O-β-glucuronide (L-10-G) vivo.

Objective: To explore the effects of breast cancer resistance protein (Bcrp) and multidrug resistance protein 2 (Mrp2) on the disposition of L-10-G.

Methods: The pharmacokinetics, tissue distribution and intestinal perfusion of Leo were studied by using efflux transporter gene knockout mouse models. The enzyme kinetics via liver and intestinal microsomes were also examined.

Results: After intravenous injection with Leo, the AUC0-∞ values of L-10-G in Bcrp1-/- and Mrp2-/- mice were 1.55-fold and 16.80-fold higher, respectively, than those in wild-type FVB mice (P < 0.05). After oral administration, the AUC0-∞ value of L-10-G showed a 2.82-fold increase in Mrp2-/- mice compared with wild-type FVB mice (P < 0.05). After gavage with Leo for 10 and 25 min, the bile accumulation of L-10-G in Mrp2-/- mice was 3-fold and 22-fold lower, respectively, than that in wild-type FVB mice (P < 0.05). Besides, the intestinal excreted amount of L-10-G showed 2.22-fold and 2.68-fold decrease in Bcrp1-/- and Mrp2-/- mice, respectively, compared with that in wild-type FVB mice (P < 0.05). The clearance of L-10-G decreased in liver microsomes and increased in intestinal microsomes of Bcrp1-/- and Mrp2-/- mice compared to the wild-type FVB mice (P < 0.05).

Conclusion: Both Bcrp and Mrp2 are involved in the disposition of L-10-G, and Mrp2 exhibits a superior influence.
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http://dx.doi.org/10.2174/1389200221999201116142742DOI Listing
January 2020

Mdr1a, Bcrp and Mrp2 regulate the efficacy and toxicity of mesaconitine and hypaconitine by altering their tissue accumulation and in vivo residence.

Toxicol Appl Pharmacol 2020 12 7;409:115332. Epub 2020 Nov 7.

International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510006, PR China. Electronic address:

Mesaconitine (MA) and hypaconitine (HA) are the main bioactive/toxic alkaloids of Aconitum carmichaelii Debx, and MDR1, BCRP and MRP2 are involved in their efflux in vitro. This study aimed to explore the effects of Mdr1a, Bcrp and Mrp2 on the efficacy/toxicity of MA and HA by using efflux transporter gene knockout mouse models. The analgesic and anti-inflammatory effects, neurotoxicity/cardiotoxicity, and pharmacokinetic profiles of MA and HA were studied. Compared to wild-type mice, the analgesic effects of MA or HA were significantly enhanced in Mdr1a, Bcrp1 and Mrp2 mice, and the anti-inflammatory effects notably increased in Bcrp1 and Mrp2 mice. Compared to wild-type mice, Mdr1a, Bcrp1 and Mrp2 mice suffered from severe karyopyknosis and edema in the brain after MA or HA treatment. Meanwhile, significant arrhythmia appeared, and the heart rate and RR-interval were greatly altered in Mdr1a, Bcrp1 and Mrp2 mice. Additionally, obvious disorder of cardiomyocytes were observed, and the CK and cTnT (indicators of heart injury) levels were greatly enhanced in efflux transporter gene knockout mice. The brain levels of MA and HA were markedly increased in Mdr1a, Bcrp1 and Mrp2 mice, and the heart levels of MA and HA enhanced greatly in Mdr1a mice. The MRT values of MA and HA were remarkably enhanced in most efflux transporter gene knockout mice. In conclusion, Mdr1a, Bcrp and Mrp2 were all involved in regulating the efficacy/toxicity of MA and HA by altering their tissue accumulation and in vivo residence. Among the three efflux transporters, Mdr1a had a superior regulatory effect.
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http://dx.doi.org/10.1016/j.taap.2020.115332DOI Listing
December 2020

MiR-125a-5p inhibits cell proliferation, cell cycle progression, and migration while promoting apoptosis in head and neck cancers by targeting ERBB3.

Auris Nasus Larynx 2021 Jun 16;48(3):477-486. Epub 2020 Oct 16.

Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China; The Second School of Clinical Medicine, Southern Medical University. Electronic address:

Objective: Head and neck cancer is one of the most common cancer types worldwide. MicroRNAs play a vital regulatory role in the occurrence and development of cancer. The objective of this study is to explore the mechanism of miR-125a-5p in the proliferation, migration and apoptosis of head and neck cancer cells and define its target genes.

Methods: The effects of miR-125a-5p on head and neck cancer cells proliferation, cell cycle distribution, apoptosis and migration were evaluated by colony formation, BrdU assay, flow cytometry and transwell assays. The potential target gene of miR-125a-5p was determined by luciferase activity assay and western blot analysis.

Results: In this study, overexpression of miR-125a-5p significantly inhibited the proliferation of head and neck cancer cells, whereas inhibition of miR-125a-5p enhanced their proliferation. BrdU assay and flow cytometry revealed that miR-125a-5p might inhibit the proliferation of cancer cells by causing cell cycle arrest. Cell apoptosis assay and Transwell assay indicated that miR-125a-5p induced cell apoptosis and inhibited cell migration of cancer cells. Other experiments confirmed that miR-125a-5p could significantly downregulate its expression by binding to ERBB3 to inhibit proliferation and ERBB3 could at least partially mediate the inhibition of miR-125a-5p on the proliferation of head and neck cancer cells.

Conclusion: The findings of this study suggested that the miR-125a-5p/ERBB3 axis might play a role in the proliferation, regulation of cell cycle, migration and apoptosis of head and neck cancer cells, potentially offering a new target for treatments of head and neck cancers.
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http://dx.doi.org/10.1016/j.anl.2020.10.001DOI Listing
June 2021
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