Publications by authors named "Liping Zhou"

187 Publications

Alteration of Autonomic Nervous System Is Associated With Severity and Outcomes in Patients With COVID-19.

Front Physiol 2021 19;12:630038. Epub 2021 May 19.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Previous studies suggest that coronavirus disease 2019 (COVID-19) is a systemic infection involving multiple systems, and may cause autonomic dysfunction.

Objective: To assess autonomic function and relate the findings to the severity and outcomes in COVID-19 patients.

Methods: We included consecutive patients with COVID-19 admitted to the 21st COVID-19 Department of the east campus of Renmin Hospital of Wuhan University from February 6 to March 7, 2020. Clinical data were collected. Heart rate variability (HRV), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and lymphocytes and subsets counts were analysed at two time points: nucleic-acid test positive and negative. Psychological symptoms were assessed after discharge.

Results: All patients were divided into a mild group (13) and a severe group (21). The latter was further divided into two categories according to the trend of HRV. Severe patients had a significantly lower standard deviation of the RR intervals (SDNN) ( < 0.001), standard deviation of the averages of NN intervals (SDANN) ( < 0.001), and a higher ratio of low- to high-frequency power (LF/HF) ( = 0.016). Linear correlations were shown among SDNN, SDANN, LF/HF, and laboratory indices ( < 0.05). Immune function, D-dimer, and NT-proBNP showed a consistent trend with HRV in severe patients ( < 0.05), and severe patients without improved HRV parameters needed a longer time to clear the virus and recover ( < 0.05).

Conclusion: HRV was associated with the severity of COVID-19. The changing trend of HRV was related to the prognosis, indicating that HRV measurements can be used as a non-invasive predictor for clinical outcome.
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http://dx.doi.org/10.3389/fphys.2021.630038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170133PMC
May 2021

An injectable and biodegradable nano-photothermal DNA hydrogel enhances penetration and efficacy of tumor therapy.

Biomater Sci 2021 May 28. Epub 2021 May 28.

Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China.

The biological barrier of solid tumors hinders deep penetration of nanomedicine, constraining anticancer treatment. Moreover, the inherent multidrug resistance (MDR) of cancer tissues may further limit the efficacy of anti-tumor nanomedicine. We synthesized highly permeable, photothermal, injectable, and positively charged biodegradable nucleic acid hydrogel (DNA-gel) nanoparticles to deliver cancer drugs. The nanoparticles are derived from photothermal materials containing black phosphorus quantum dots (BPQDs). The intra-tumoral BPQDs improve the sensitivity of tumor cells to photothermal therapy (PTT) and photodynamic treatment (PDT). Tumor cells take up the positively charged and controllable size DNA-gel nanoparticles, facilitating easy penetration and translocation of the particles across and within the cells. Mouse models demonstrated the anti-tumor activity of the DNA gel nanoparticles in vivo. In particular, the DNA gel nanoparticles enhanced clearance of both small and large tumor masses. Just 20 days after treatment, the tumor masses had been cleared. Compared to DOX chemotherapy alone, the DNA-gel treatment also significantly reduced drug resistance and improved the overall survival of mice with orthotopic breast tumors (83.3%, 78 d). Therefore, DNA gel nanoparticles are safe and efficient supplements for cancer therapy.
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http://dx.doi.org/10.1039/d1bm00568eDOI Listing
May 2021

Robust incident angle calibration of angle-resolved ellipsometry for thin film measurement.

Appl Opt 2021 May;60(13):3971-3976

Angle-resolved ellipsometry with back focal plane imaging has been found to be of increasing importance in recent industrial sensing by virtue of its rich information provided at various incident and azimuthal angles. To achieve high sensing accuracy, the incident angles of a back focal plane must be accurately calibrated. For this purpose, a simple and robust incident angle calibration method based on full-field Brewster angle fitting is proposed, without expensive tools or complex operations. With this method, a back focal plane image is first captured from boundary reflectance through a high-numerical-aperture objective. By extracting annular data from the image, radius-dependent ellipsometric parameters $ (\psi,{\Delta)}$ are calculated. At the end, the radii of the back focal plane are mapped to the angle of incidence by using a fitted Brewster angle as the reference. The method is validated by simulation and experiments using a homemade angle-resolved ellipsometer and a commercial spectroscopic ellipsometer. The results show that the proposed method provides a 75% error reduction approximately from generally used methods.
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http://dx.doi.org/10.1364/AO.419357DOI Listing
May 2021

The lead burden of occupational lead-exposed workers in Guangzhou, China: 2006-2019.

Arch Environ Occup Health 2021 May 12:1-12. Epub 2021 May 12.

Guangzhou Occupational Disease Prevention and Treatment Hospital, Guangzhou, China.

We analyzed the lead levels in blood and urine from lead-exposed workers in Guangzhou and assessed the influencing factors. The data were analyzed by descriptive statistics, and the time-dependent changes were mapped via analytical statistics. Although the lead burden showed a clear downward trend over time, it remained high among the exposed workers. The highest lead burden was detected in workers of the electrical equipment manufacturing industry, especially among those in lead-acid battery factories where we did field studies. Hazardous as the working conditions of the original lead-acid battery factories were, there were improvements in the applications of occupational disease prevention measures after the relocation of factories, but the lead burdens were still above the average levels of lead-related industries. Improvements are needed in the management and regulations on occupational safety and health to further decrease the lead burden to acceptable levels.
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http://dx.doi.org/10.1080/19338244.2021.1916421DOI Listing
May 2021

Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells.

Exp Ther Med 2021 Jun 14;21(6):619. Epub 2021 Apr 14.

College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zheijiang 310053, P.R. China.

Induced pluripotent stem cells (iPSCs) reprogrammed by somatic cells may be used as a potentially novel treatment regimen in stem cell regenerative medicine, particularly in the central nervous system (CNS). In the present study, iPSCs were generated using mouse embryonic fibroblasts by ectopic overexpression of Sox-2, Oct-3/4, Klf-4 and c-Myc, and cultured under the same conditions as that used for embryonic stem cells. The neuronal differentiation capacity of mouse iPSCs was examined, and the involvement of the formation of embryoid bodies was assessed. The results suggested that after 15 days of neuronal inducement, Nestin, Vimentin and Glast protein expression levels were significantly increased in the mouse iPSC-derived cells. Additionally, Bmi1, which is selectively expressed in differentiated postnatal adult stem cells. such as hematopoietic stem cells and neural stem cells, was required for establishment of the neuronal differentiation of mouse iPSCs. In order to assess the effects of Bmi1 in neuronal differentiation, Bmi1 expression levels were inhibited with the small molecule PTC-209. The results showed that inhibition of Bmi1 expression reduced the expression of neuronal markers, such as Nestin, compared with the controls. These results suggested that mouse iPSCs can be induced to achieve neuronal differentiation. More interestingly, Bmi1 was required during the neuronal differentiation of mouse iPSCs.
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http://dx.doi.org/10.3892/etm.2021.10051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082597PMC
June 2021

Water extract of Er-xian decoction selectively exerts estrogenic activities and interacts with SERMs in estrogen-sensitive tissues.

J Ethnopharmacol 2021 Jul 3;275:114096. Epub 2021 Apr 3.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057, PR China. Electronic address:

Ethnopharmacological Relevance: The increasing use of "kidney"-nourishing Traditional Chinese Medicine (TCM) like Er-xian decoction (EXD) for management of menopausal symptoms and osteoporosis has aroused concerns about their safety, and whether they interact with prescription drugs as both of them act via estrogen receptors (ERs) and regulate serum estradiol.

Aim Of The Study: The present study aimed to evaluate whether EXD selectively exerted estrogenic activities and interacted with Selective Estrogen Receptor Modulators (SERMs).

Materials And Methods: In vivo, mature ovariectomized (OVX) rats were administrated with EXD or combined treatment of EXD and SERMs for 12 weeks. The tissue-selective effect of EXD and its interaction of SERMs were studied in four estrogen sensitive tissues, bone, brain, breast and uterus. In vitro, the interaction of extracts of EXD-treated serum and SERMs in four ER-positive cell lines.

Results: In OVX rats, EXD selectively alleviated estrogen deficiency-induced changes in the bone and brain without inducing any estrogenic effects in the breast or uterus. Two-way ANOVA indicated the presence of interactions between EXD and SERMs in OVX rats but EXD did not significantly alter the tissue responses to SERMs in the bone, breast or brain. Indeed, the combined use of EXD and SERMs appeared to suppress the estrogenic effect of raloxifene and tamoxifen in the uterus. Extract of EXD-treated serum directly stimulated cell proliferation or differentiation in human osteosarcoma MG-63, neuroblastoma SHSY5Y, breast cancer MCF-7, and endometrial Ishikawa cells. Two-way ANOVA revealed that EXD-treated serum interacted with SERMs at various concentrations and altered the effects of tamoxifen in MG-63 and MCF-7 cells.

Conclusions: EXD exerted estrogenic effects in a tissue-selective manner and interacted with SERMs. Combined treatment of EXD and SERMs did not hamper the beneficial effects of SERMs on the bone or brain but appeared to moderate the estrogenic effect of SERMs in the uterus.
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http://dx.doi.org/10.1016/j.jep.2021.114096DOI Listing
July 2021

Identification of Differential Expression Cytokines in Hemolysis, Elevated Liver Enzymes, and Low Platelet Syndrome by Proteome Microarray Analysis and Further Verification.

Cell Transplant 2021 Jan-Dec;30:963689720975398

Department of Gynecology and Obstetrics, 105860The Second Affiliated Hospital of Soochow University, Suzhou, China.

To screen the differential expression cytokines (DECs) in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, establish its differential cytokines spectra, and provide the clues for its diagnosis and pathogenic mechanism researches. Sera from four HELLP syndrome patients and four healthy controls were detected by proteome microarray. Then the analysis of Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network were performed and possible hub proteins were selected out, further verified by Enzyme Linked Immunosorbent Assay (ELISA) in sera from 21 HELLP syndrome patients and 21 healthy controls. Thirty DECs were defined according to -value and fold change between HELLP group and control group. GO enrichment analysis showed that DECs were mainly involved in the regulation of inflammatory response and have relationship to growth factor binding, transmembrane receptor protein kinase, and cytokine receptor activity. Seven possible hub proteins were defined by PPI analysis, including IGFBP-3/Follistatin-like 1/FLRG/Fetuin A and MMP-13/Thrombospondin-5/Aggrecan. ELISA showed higher serum levels of Fetuin A/IGFBP-3/FLGR/MMP-13/Thrombospondin-5 in HELLP group than those in controls, while the levels of Follistatin-like 1 and Aggrecan were lower in HELLP patients (all < 0.05 or <0.01).The serological DECs spectra of HELLP syndrome was established and seven possible hub proteins that may be more closely related to the disease have been verified, providing new clues for its pathogenesis, diagnosis, and clinical treatment.
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http://dx.doi.org/10.1177/0963689720975398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995311PMC
March 2021

TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression.

Front Cell Dev Biol 2021 4;9:645402. Epub 2021 Mar 4.

Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China.

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.
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http://dx.doi.org/10.3389/fcell.2021.645402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970191PMC
March 2021

The occurrence and potential predictive factors of major adverse cardiac and cerebral events in end-stage renal disease patients on continuous ambulatory peritoneal dialysis: A prospective cohort study.

Medicine (Baltimore) 2021 Mar;100(10):e24616

Department of Nephrology, Zhongshan Hospital Xiamen University, Xiamen.

Abstract: Major adverse cardiac and cerebral events (MACCE) are common complications, which prolong hospitalization and increase mortality rate in end-stage renal disease (ESRD) patients who underwent continuous ambulatory peritoneal dialysis (CAPD). Therefore, this study aimed to investigate MACCE occurrence and its potential predictive factors in those patients.In this prospective cohort study, 196 diagnosis of ESRD patients who underwent CAPD treatment in our hospital were eligible, and their clinical data (including demographic data and biochemical indexes) were documented. Besides, their MACCE occurrence was assessed within 3-year follow-up period.In patients, 1-, 2-, and 3-year MACCE occurrence rates were 5.1%, 11.7%, and 14.8%, respectively. Meanwhile, the mean duration of accumulating MACCE occurrence was 33.1 (95% confidence interval: 32.0-34.2) months. Furthermore, age, peritoneal dialysis duration (PDD), C-reactive protein (CRP), fasting blood glucose (FBG) and total cholesterol high correlated with increased accumulating MACCE occurrence, while high-density lipoprotein cholesterol (HDL-C) high correlated with decreased accumulating MACCE occurrence. Notably, by further multivariate Cox's proportional hazard regression analysis, age, PDD, CRP, serum uric acid, and FBG high were independent predictive factors for raised accumulating MACCE occurrence, while HDL-C high was an independent predictive factor for attenuated accumulating MACCE occurrence.MACCE are common; besides, age, peritoneal dialysis duration, C-reactive protein, serum uric acid, fasting blood glucose, and high-density lipoprotein cholesterol serve as potential markers for indicating MACCE in ESRD patients who underwent CAPD.
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http://dx.doi.org/10.1097/MD.0000000000024616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969313PMC
March 2021

Humanin alleviates insulin resistance in polycystic ovary syndrome: a human and rat model-based study.

Endocrinology 2021 Mar 10. Epub 2021 Mar 10.

Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, China.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.
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http://dx.doi.org/10.1210/endocr/bqab056DOI Listing
March 2021

A Critical Review of the Effect of Dietary Fiber Intake on the Prevention of Colorectal Cancer in Eastern Asian Countries.

J Healthc Eng 2021 16;2021:6680698. Epub 2021 Jan 16.

Xiangya School of Nursing, Central South University, Changsha, Hunan, China.

Background: Colorectal cancer has become the second most common type of cancer in females and the third most common type of cancer in males. The incidence rate of colorectal cancer is increasing along with the change of lifestyle and dietary habits in East Asia. The cause of colorectal cancer is complex; environmental factors and genetic factors affect each other. Dietary fiber is considered as the prevention of colorectal cancer. Epidemiological data in Europe and America have suggested that dietary fiber intake is negatively correlated with colorectal cancer incidence rate. However, the evidence among different populations is inconsistent, and little is known about these associations in Eastern Asian areas.

Objectives: To critically review all available human epidemiological data on the relationship between dietary fiber intake and colorectal cancer in Eastern Asian countries and make recommendations for these populations. . PubMed and Embase were used to search online research papers regarding the relationship between dietary fiber intake and the risk of colorectal cancer in Eastern Asian. We located 9 publications, of which the sample size ranged from 266 to 78, 326.

Results: Five case-control studies, as well as one prospective study, have examined significant preventive effects of dietary fiber intake on the risk of colorectal cancer while evidence from three prospective cohorts suggested no preventive effects of dietary fiber intake on colorectal cancer among these populations. There is no consistent conclusion on the protective effect of dietary fiber from different sources and types.

Conclusion: The association between dietary fiber intake and colorectal cancer risk in Chinese, Japanese, and Korean is considered to be plausible by the available literature. This current review cannot substantiate the preventive effect of dietary fiber intake on colorectal cancer due to the limited available evidence analyzed.
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http://dx.doi.org/10.1155/2021/6680698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834794PMC
January 2021

Selective Estrogen Receptor Modulator-Like Activities of Herba epimedii Extract and its Interactions With Tamoxifen and Raloxifene in Bone Cells and Tissues.

Front Pharmacol 2020 15;11:571598. Epub 2021 Jan 15.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.

(HEP), a kidney-tonifying herb, has been commonly used alone or in formula for strengthening kidney function and treating bone disorders. Its bone protective activity has been demonstrated to be via estrogen receptor (ERs). HEP activates the phosphorylation of ERα in an estrogen response element- (ERE-) dependent manner. We examined the bone protective effects of HEP and its potential interactions with Selective Estrogen Receptor Modulators (SERMs, such as tamoxifen and raloxifene) as they act via the same ERs. Six-month-old mature Sprague Dawley sham-operated (Sham) or ovariectomized (OVX) rats were treated with either vehicle, 17ß-estradiol (1.0 mg/kg.day), tamoxifen (Tamo, 1.0 mg/kg.day), raloxifene (Ralo, 3.0 mg/kg.day), HEP (0.16 g/kg.day), or its combinations with respective SERMs (HEP + Tamo; HEP + Ralo) for 12 weeks. HEP and SERMs as well as their combinations significantly restored changes in bone mineral density (BMD), trabecular bone properties, and bone turnover biomarkers induced by ovarian sex hormone deficiency in ovariectomized rats. Besides the increase in serum estradiol, inhibition on follicle stimulating hormone (FSH) might also be involved in the osteoprotective activities of HEP and SERMs. HEP interacted with SERMs to protect bones from ovarian sex hormone deficiency without altering SERMs' bone protective activities. HEP neither induced changes in uterus weight nor altered the uterotrophic activity of SERMs in OVX rats. In human osteosarcoma MG-63 cells, HEP-treated serum (HEP-Ts) significantly promoted alkaline phosphatase (ALP) activity like the crude HEP extract did but did not stimulate ERE activity. Our study also reported that biologically activated HEP interacted with SERMs to promote ALP activity without altering the action of SERMs at most of the concentrations tested in MG-63 cells. HEP exerted bone protective activity and the use of HEP did not alter the bone protective activities of SERMs when they were used simultaneously in an estrogen-deficient rat model.
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http://dx.doi.org/10.3389/fphar.2020.571598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843570PMC
January 2021

Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing.

Nat Commun 2021 01 12;12(1):287. Epub 2021 Jan 12.

Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Bioelectrical impulses intrinsically generated within the sinoatrial node (SAN) trigger the contraction of the heart in mammals. Though discovered over a century ago, the molecular and cellular features of the SAN that underpin its critical function in the heart are uncharted territory. Here, we identify four distinct transcriptional clusters by single-cell RNA sequencing in the mouse SAN. Functional analysis of differentially expressed genes identifies a core cell cluster enriched in the electrogenic genes. The similar cellular features are also observed in the SAN from both rabbit and cynomolgus monkey. Notably, Vsnl1, a core cell cluster marker in mouse, is abundantly expressed in SAN, but is barely detectable in atrium or ventricle, suggesting that Vsnl1 is a potential SAN marker. Importantly, deficiency of Vsnl1 not only reduces the beating rate of human induced pluripotent stem cell - derived cardiomyocytes (hiPSC-CMs) but also the heart rate of mice. Furthermore, weighted gene co-expression network analysis (WGCNA) unveiled the core gene regulation network governing the function of the SAN in mice. Overall, these findings reveal the whole transcriptome profiling of the SAN at single-cell resolution, representing an advance toward understanding of both the biology and the pathology of SAN.
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http://dx.doi.org/10.1038/s41467-020-20448-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804277PMC
January 2021

Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolomics and Lipidomics Identify Biomarkers for Efficacy Evaluation of Mesalazine in a Dextran Sulfate Sodium-Induced Ulcerative Colitis Mouse Model.

J Proteome Res 2021 02 23;20(2):1371-1381. Epub 2020 Dec 23.

MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China.

This study aims to identify biomarkers for evaluating the therapeutic efficacy of mesalazine on ulcerative colitis by metabolomics and lipidomics. A dextran sulfate sodium-induced mouse model was used. The disease status was assessed by a disease activity index, the TNF-α level of colon was measured by an enzyme-linked immunosorbent assay, and the pathological changes of colon tissue was examined by hematoxylin-eosin staining. Serum metabolomics and lipidomics analysis based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were applied to decipher the metabolic profile changes. Multivariate analysis was applied to differentiate the metabolites of controls, models, and mesalazine-treated mice. By the receiver operating characteristic (ROC) analysis, 40 differential metabolites with an area under curve (AUC) >0.80 were screened out between control and model groups. Among them, four potential biomarkers (palmitoyl glucuronide, isobutyrylglycine, PC (20:3 (5Z, 8Z, 11Z)/15:0) and L-arginine) had a signficantly reversed level of peak areas in the mesalazine group, and three of them were closely correlated with mesalazine efficacy by linear regression analysis. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in colitis mice, including glycerophospholipid metabolism, pyrimidine metabolism, linoleic acid metabolism, arginine biosynthesis, etc. This study indicates that serum metabolomics is a useful approach that can noninvasively evaluate the therapeutic effect and provide unique insights into the underlying mechanism of mesalazine.
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http://dx.doi.org/10.1021/acs.jproteome.0c00757DOI Listing
February 2021

Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling.

Phytomedicine 2021 Feb 19;82:153413. Epub 2020 Nov 19.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China. Electronic address:

Background: Rapid, non-genomic estrogen receptor (ER) signaling plays an integral role in mediating the tissue selective properties of ER modulators. Icariin, a bone bioactive flavonoid, has been reported to selectively activate non-genomic ERα signaling in in vitro and in vivo studies.

Purpose: The mechanisms underlying the estrogen-like bone protective effects of icariin are not fully understood, especially those that are related to insulin-like growth factor I (IGF-1) signaling. The bone protective effects of icariin were investigated in female mature ovariectomized (OVX) rats and the signaling of IGF-IR- ERα cross-talk was determined in osteoblastic cells.

Study Design And Methods: Icariin at 3 different dosages (50, 500 and 3000 ppm) were orally administrated to rats for 3 months through daily intake of phytoestrogen-free animal diets containing icariin. Bone marrow stromal cells (BMSCs) and osteoclast precursors from femurs were harvested for experiments and RNA-sequencing. The interactions between IGF-IR and non-genomic ERα signaling were examined in pre-osteoblastic MC3T3-E1 cells and mature osteoblasts differentiated from BMSCs.

Results: Our results show that chronic administration of icariin to OVX rats significantly protected them against bone loss at the long bone and lumbar spine without inducing any uterotrophic effects. Ex vivo studies using BMSCs and osteoclast precursors confirmed the stimulatory effects of icariin on osteoblastogenesis and its inhibitory effects on osteoclastogenesis, respectively. RNA-sequencing analysis of mRNA from BMSCs revealed that icariin at 500 ppm significantly altered IGF-1 signaling as well as PI3K-Akt pathways. Our results demonstrated for the first time the rapid induction of interactions between IGF-IR and ERα as well as IGF-IR signaling and the downstream Akt phosphorylation by icariin in MC3T3-E1 cells. The activation of ERα and Akt phosphorylation by icariin in MC3T3-E1 cells and the osteogenic effects of icariin on ALP activity in mature osteoblasts were shown to be IGF-IR-dependent.

Conclusion: Our findings reveal that icariin activates both ERα and Akt via enhancing rapid induction of IGF-1 signaling in osteoblastic cells for osteogenesis and might be regarded as a novel pathway-selective phytoestrogen for management of postmenopausal osteoporosis.
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http://dx.doi.org/10.1016/j.phymed.2020.153413DOI Listing
February 2021

Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway.

Mol Hum Reprod 2021 02;27(2)

Department of Reproduction and Genetics, The First affiliated Hospital of Kunming Medical University, Kunming, China.

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, whereas the pathogenesis is still not fully understood. Systemic and ovarian oxidative stress (OS) imbalance is a pivotal feature of PCOS. Humanin, a mitochondria-derived peptide, has been reported to function as an antioxidant in cardiomyocytes, pancreatic beta cells and other cells, but how this function is regulated remains unclear. In this study, we investigated whether humanin expression differs in the granulosa cells (GCs) of PCOS patients versus controls, and whether humanin alleviates OS in PCOS ovaries. Sixteen PCOS patients and 28 age- and BMI-matched controls undergoing IVF were recruited, and their serum, follicular fluid and GCs were collected for humanin analysis. Dehydroepiandrosterone-induced rat PCOS models, and vitamin K3-induced OS COV434 cell lines were applied to investigate the mechanism. Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients. Exogenous humanin supplementation significantly attenuated body weight gain, ovarian morphological abnormalities, endocrinological disorders and ovarian and systemic OS in PCOS rat models. Our study further demonstrated that this attenuation effect was involved in the modulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. In summary, this study reported for the first time that decreased expression of humanin in the GCs was associated with oxidative imbalance in PCOS. Humanin alleviates OS in ovarian GCs of PCOS patients via modulation of the Keap1/Nrf2 signalling pathway.
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http://dx.doi.org/10.1093/molehr/gaaa081DOI Listing
February 2021

Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGF3-Smad2/3-Nedd9 Signaling Pathway.

Neural Plast 2020 13;2020:8886715. Epub 2020 Nov 13.

College of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, China.

Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-3 (TGF3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGF3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGF3-SMAD2/3-NEDD9 pathway.
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http://dx.doi.org/10.1155/2020/8886715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683137PMC
November 2020

Expression of and Correlates with Prognosis in Patients with Breast Cancer After Radiotherapy: A Case-Control Study.

Cancer Biother Radiopharm 2020 Oct 28. Epub 2020 Oct 28.

Graduate Faculty, The First Hospital of China Medical University, Shenyang, People's Republic of China.

This study aims to explore the associations of human epidermal growth factor receptor 2 () and breast cancer susceptibility gene 1 () expression levels with prognosis and radiation sensitivity in patients with breast cancer. Breast cancer tissues, adjacent normal breast tissues, and benign breast lesions were initially obtained from 256 breast cancer patients as well as an additional 245 patients with breast lesions. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to assess the expression of and in the collected tissues. Immunohistochemistry was performed to examine and -positive expression levels in the tissues. The relationship between and expression levels and radiation sensitivity as well breast cancer prognosis was assessed by the Spearman correlation analysis and Kaplan-Meier survival analysis. Compared with adjacent normal breast tissues and benign breast lesions, the breast cancer tissues exhibited high expression of mRNA and protein and low expression of mRNA and protein. Patients with positive expression had a significantly shorter survival time, and survival time of patients with positive expression was markedly longer, which were consistent with RT-qPCR results. After radiotherapy, the local failure rate of -positive patients was higher than that of the negative ones, while that of -positive patients was lower than that of the negative ones. This study suggested that breast cancer patients with high expression and low expression were less sensitive to radiotherapy with poor prognosis in breast cancer.
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http://dx.doi.org/10.1089/cbr.2020.3607DOI Listing
October 2020

A standardized extract of Danggui Buxue Tang decoction selectively exerts estrogenic activities distinctly from tamoxifen.

Phytother Res 2021 Mar 15;35(3):1456-1467. Epub 2020 Oct 15.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.

More and more menopausal women use Danggui Buxue Tang (DBT) for relieving their symptoms. Concerns for its safety have been raised as it contains phytoestrogen and acts via estrogen receptors (ERs). Our study aimed to determine whether DBT could selectively exert estrogenic activities and interact with tamoxifen in bone, brain, uterus, and breast by using ovariectomized (OVX) rats and ER-positive cells. In OVX rats, DBT induced a 31.4% increase in bone mineral density and restored the mRNA expression of dopamine biomarker in striatum, 3.32-fold for tyrosine hydrolase (p < .001) and 0.21-fold for dopamine transporter (p < .001), which was similar to tamoxifen; tamoxifen, but not DBT, increased uterus weight and Complement component 3 expression by more than twofold (p < .001); unlike tamoxifen, DBT induced mild proliferation in mammary gland. Two-way ANOVA indicated the interactions between them in OVX rats (p < .05) but DBT did not alter the responses to tamoxifen. DBT stimulated proliferation or differentiation and estrogen response element in MCF-7, MG-63, Ishikawa, and SHSY5Y cells and altered the effects of tamoxifen. In summary, DBT exerted estrogenic effects in tissue-selective manner, which was different from tamoxifen. DBT interacted with tamoxifen but did not significantly alter its effects in OVX rats.
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http://dx.doi.org/10.1002/ptr.6909DOI Listing
March 2021

Facilitating Granule Cell Survival and Maturation in Dentate Gyrus With Baicalin for Antidepressant Therapeutics.

Front Pharmacol 2020 2;11:556845. Epub 2020 Sep 2.

College of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Baicalin isolated from possesses antidepressant abilities through its relation to hippocampal neurogenesis. Current research has found that baicalin can promote the proliferation of hippocampal granule cells, however, the detailed mechanism of baicalin on the survival and maturation of hippocampal granule cells has yet to be sufficiently explored. The purpose of this study was to evaluate whether baicalin could facilitate the survival and maturation of hippocampal granule cells, and to explore its potential mechanism. The chronic corticosterone (CORT)-induced mouse model of depression was used to assess antidepressant-like effects of baicalin and to illuminate possible molecular mechanisms by which baicalin affects hippocampal neurogenesis. The survival and maturation of granule cells were measured by immunohistochemistry, immunofluorescence and Golgi staining. The expression of Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β)/β-catenin pathway related proteins were measured by western blot analysis. PI3K inhibitor LY292002 and AKT inhibitor Perifosine were administered to HT-22 cells to explore the relationship between the PI3K/AKT/GSK3β/β-catenin pathway and baicalin. The results of the study illustrated that baicalin significantly decreased chronic CORT-induced depressive-like behaviors and reduced serum corticosterone levels. In addition, baicalin (administered at 60 mg/kg) reversed chronic CORT-induced lesions on hippocampal granule cells. Moreover, baicalin significantly increased the phosphorylation rate of PI3K, AKT, GSK3β, and total β-catenin. The study found that administration of LY292002/Perifosine counteracted the effects of baicalin in HT-22 cells. These results demonstrate that baicalin can alleviate chronic CORT-induced depressive-like behaviors through promoting survival and maturation of adult-born hippocampal granule cells and exhibiting protective effect on hippocampal neuron morphology. We propose the underlying mechanisms involve the activation of the PI3K/AKT/GSK3β/β-catenin pathway.
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http://dx.doi.org/10.3389/fphar.2020.556845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493074PMC
September 2020

LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration.

Cell Res 2021 Apr 24;31(4):450-462. Epub 2020 Sep 24.

Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.
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http://dx.doi.org/10.1038/s41422-020-00411-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114926PMC
April 2021

Identification of Key Prognostic Biomarker and Its Correlation with Immune Infiltrates in Pancreatic Ductal Adenocarcinoma.

Dis Markers 2020 31;2020:8825997. Epub 2020 Aug 31.

Department of Graduate Faculty, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.
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http://dx.doi.org/10.1155/2020/8825997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479484PMC
August 2020

[Composition and analysis of fatty acids in freshwater products in Hunan Province in 2014].

Wei Sheng Yan Jiu 2020 Jul;49(4):554-560

Hunan Provincial Center for Disease Control and Prevention, Changsha 410008, China.

Objective: To investigate the nutritional composition of fatty acids in freshwater products in Hunan Province.

Methods: The edible parts of freshwater products were detected by gas chromatography, and fatty acid fingerprints were obtained by statistical analysis.

Results: A total of 18 freshwater products were monitored and 14-26 fatty acids were detected in each freshwater product. Among them, 12 were saturated fatty acids(SFA), ranging from 0. 74 to 3143 mg/100 g, 9 were monounsaturated fatty acids(MUFA), ranging from 1. 23 to 2790 mg/100 g, and 10 were polyunsaturated fatty acids(PUFA), ranging from 1. 75 to 2832 mg/100 g. The ratio of n-6 to n-3 in polyunsaturated fatty acids ranged from 0. 24∶1 to 15. 7∶1.

Conclusion: The composition of fatty acids in freshwater products in Hunan Province is mainly unsaturated fatty acids. Most freshwater products are rich in n-3 PUFA, and the ratio of n-6 PUFA to n-3 PUFA is less than 6, which is beneficial to the nutritional balance. The composition and content of fatty acids have ideal nutritional value.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2020.04.005DOI Listing
July 2020

Characterization of Spray Dried Particles Through Microstructural Imaging.

J Pharm Sci 2020 11 3;109(11):3404-3412. Epub 2020 Aug 3.

Merck & Co., Inc., West Point, PA 19486, USA.

Spray drying is commonly used to produce amorphous solid dispersions (ASD) to improve the bioperformance of poorly water-soluble drugs. In this study, imaging techniques such as focused ion beam-scanning electron microscopy (FIB-SEM) and X-ray microcomputed tomography (XRCT) were used to study the microstructure of spray dried (SD) particles. Spray drying at higher outlet temperature (T) was found to produce more spherical hollow particles with smooth surface and thinner walls, while more raisin-like particles with thicker walls were generated at lower T. For the first time, an artificial intelligence-facilitated XRCT image analysis tool was developed to make quantitative analysis of thousands of particles individually possible. The particle size distribution through XRCT image analysis is generally in line with what is measured by laser diffraction. The image analysis reveals envelope density as a more sensitive physical attribute for process change than conventional bulk/tap density. Further, the tensile strength of SD particle compacts correlates with the particle wall thickness, and this is likely caused by the larger interparticle contact area generated by more deformation of particles with thinner walls. The knowledge gained here can help enable SD particle engineering and drug product with more robust process and optimized performance.
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http://dx.doi.org/10.1016/j.xphs.2020.07.032DOI Listing
November 2020

Physically Crosslinked Hydrogels Based on Poly (Vinyl Alcohol) and Fish Gelatin for Wound Dressing Application: Fabrication and Characterization.

Polymers (Basel) 2020 Aug 2;12(8). Epub 2020 Aug 2.

Marine College, Shandong University, Wenhua West Road, Gao Strict, Weihai 264209, China.

We developed the interpenetrating double network composite hydrogel based on poly (vinyl alcohol) (PVA) and fish gelatin (FG) via thermal treatment and repeated freeze-thawing. A function of salicylic acid was incorporated into the hydrogel to improve its antibacterial properties. The color values, water contents, water evaporation rate, and swelling behavior were investigated. The drug-loading performance of the composite hydrogel was demonstrated by loading salicylic acid in various hydrogel systems. Moreover, the cumulative dissolution percentage of salicylic acid and the antibacterial activity of composite hydrogel were carried out. The results revealed that as FG concentration increased from 0% to 3.75% (/), gels changed from white to slight yellow and the swelling ratio increased from 54% to 83% (within 8 h). The presence of FG decreased the water content of gels which ranged from 86% to 89% and also decreased water evaporation rate. All gels presented the swelling index within 0.5-1.0, indicating a non-Fickian diffusion mechanism. The drug sustained dissolution behavior of pure PVA and composite hydrogel showed the same trend. Besides, the presence of the obvious bacteriostatic zones means that drug-loaded composite hydrogels have an effective antibacterial property. These results demonstrated that PVA/FG-based interpenetrating hydrogel is an appropriate biomaterial for drug-carrying wound dressing application.
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http://dx.doi.org/10.3390/polym12081729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465127PMC
August 2020

Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy: A Translational Perspective.

Circ Res 2020 06 18;127(1):51-72. Epub 2020 Jun 18.

Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen, Germany (S.N., J.H., D.D.).

Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innovation is a better understanding of underlying fundamental mechanisms. This article reviews recent advances in understanding the molecular basis for AF, with a particular emphasis on relating these new insights to opportunities for clinical translation. We first review the evidence relating basic electrophysiological mechanisms to the characteristics of clinical AF. We then discuss the molecular control of factors leading to some of the principal determinants, including abnormalities in impulse conduction (such as tissue fibrosis and other extra-cardiomyocyte alterations, connexin dysregulation and Na-channel dysfunction), electrical refractoriness, and impulse generation. We then consider the molecular drivers of AF progression, including a range of Ca-dependent intracellular processes, microRNA changes, and inflammatory signaling. The concept of key interactome-related nodal points is then evaluated, dealing with systems like those associated with CaMKII (Ca/calmodulin-dependent protein kinase-II), NLRP3 (NACHT, LRR, and PYD domains-containing protein-3), and transcription-factors like TBX5 and PitX2c. We conclude with a critical discussion of therapeutic implications, knowledge gaps and future directions, dealing with such aspects as drug repurposing, biologicals, multispecific drugs, the targeting of cardiomyocyte inflammatory signaling and potential considerations in intervening at the level of interactomes and gene-regulation. The area of molecular intervention for AF management presents exciting new opportunities, along with substantial challenges.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.316363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398486PMC
June 2020

Mesenchymal Stem Cells: A Potential Therapeutic Strategy for Neurodegenerative Diseases.

Eur Neurol 2020 20;83(3):235-241. Epub 2020 Jul 20.

College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China,

Neurodegenerative disease is a kind of chronic, progressive nervous system disease characterized by neuron degeneration or apoptosis. Current treatments cannot prevent the development of the disease. Possible alternative treatments include cell therapy, especially with the use of mesenchymal stem cells (MSCs). MSCs are pluripotent stem cells with capacities for self-renewal and multidirectional differentiation. MSCs may serve as a reliable source of neural cells for potential cell replacement therapy or regenerative medicine treatment. Here, we summarized the therapeutic mechanisms of MSCs and how they can contribute to the development of treatments for neurodegenerative diseases.
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http://dx.doi.org/10.1159/000509268DOI Listing
March 2021

Characterization of Controlled Release Microspheres Using FIB-SEM and Image-Based Release Prediction.

AAPS PharmSciTech 2020 Jul 14;21(5):194. Epub 2020 Jul 14.

DigiM Solution LLC, 67 South Bedford Street, Suite 400 West, Burlington, Massachusetts, 01803, USA.

For polymer-based controlled release drug products (e.g. microspheres and implants), active pharmaceutical ingredient distribution and microporosity inside the polymer matrix are critical for product performance, particularly drug release kinetics. Due to the decreasing domain size and increasing complexity of such products, conventional characterization and release test techniques are limited by their resolution and speed. In this study, samples of controlled release poly(lactic-co-glycolic acid) microspheres in the diameter range of 30-80 μm are investigated with focused ion beam scanning electron microscope imaging at 20 nm or higher resolution. Image data is quantified with artificial intelligence-based image analytics to provide size distributions of drug particles and pores within the microsphere sample. With an innovative image-based numerical simulation method, release profiles are predicted in a matter of days regardless of the designed release time. A mechanistic understanding on the impact of porosity to the interplays of drug, formulation, process, and dissolution was gained.
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http://dx.doi.org/10.1208/s12249-020-01741-wDOI Listing
July 2020

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing by Enhancing Angiogenesis through Delivering Angiopoietin-2.

Stem Cell Rev Rep 2021 Apr;17(2):305-317

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China.

The underlying mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes (hucMSC-Exs), which play significant roles in skin wound healing, remain poorly understood. By using a rat model of deep second-degree burn injury, the roles of hucMSC-Exs in angiogenesis and cutaneous wound healing in vivo were investigated. We found that hucMSC-Exs accelerated skin wound healing and angiogenesis, inducing a higher wound-closure rate and increased expression of CD31 in vivo. We also discovered that hucMSC-Exs contained angiopoietin-2 (Ang-2), and treatment with hucMSC-Exs enhanced the expression of the Ang-2 protein in the wound area and human umbilical vein endothelial cells (HUVECs) through exosomal-mediated Ang-2 transfer. Moreover, hucMSC-Exs promoted the proliferative, migratory, and tube-forming ability of HUVECs. Furthermore, overexpression of Ang-2 in hucMSC-Exs further enhanced HUVEC migration and tube formation and exerted therapeutic and proangiogenic effects in cutaneous wounds in rats, whereas knockdown of Ang-2 in hucMSC-Exs abrogated these therapeutic and proangiogenic effects. Taken together, our results indicated that hucMSC-Ex-derived Ang-2 plays a significant role in tube formation of HUVECs and promotion of angiogenesis, and further suggested that hucMSC-Ex-based therapy may serve as a promising therapeutic approach for promoting cutaneous wound healing.
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http://dx.doi.org/10.1007/s12015-020-09992-7DOI Listing
April 2021

One-step controllable synthesis of amino-modification siloxene for enhanced solar water-splitting.

J Colloid Interface Sci 2020 Nov 16;579:205-211. Epub 2020 Jun 16.

School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China. Electronic address:

Novel two-dimensional silicon-based material siloxene has been synthesized handily by a one-step method, which utilizes the characteristics of the topological exfoliation to simplify the process of synthesis and modification. It is worth mentioning that for the first time amino-modified derivative has been investigated. Amino modification can promote the oxidation of siloxene, enlarge the bandgap and extend the carrier lifetime of siloxene. The application of siloxene before and after modification in water-splitting has been investigated. In addition, the superiority of the resultant two-dimensional materials was concisely elaborated, which revealed that owing to more effective photogenerated carriers' separation in amino modification siloxene, hydrogen production could be greatly promoted.
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http://dx.doi.org/10.1016/j.jcis.2020.06.066DOI Listing
November 2020