Publications by authors named "Huimin Fan"

113 Publications

Therapeutic of Candesartan and Music Therapy in Diabetic Retinopathy with Depression in Rats.

Evid Based Complement Alternat Med 2021 26;2021:5570356. Epub 2021 Mar 26.

Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.
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http://dx.doi.org/10.1155/2021/5570356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018856PMC
March 2021

Myocardial ischemia-reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury.

J Extracell Vesicles 2021 Feb 23;10(4):e12072. Epub 2021 Feb 23.

Research Center for Translational Medicine Shanghai East Hospital Tongji University School of Medicine Shanghai P.R. China.

Extracellular vesicles (EVs) curb important biological functions. We previously disclosed that ischemia-reperfusion (IR) induces increased release of EVs (IR-EVs) in the heart. However, the role of IR-EVs in IR pathological process remains poorly understood. Here we found that adoptive transfer of IR-EVs aggravated IR induced heart injury, and EV inhibition by GW4869 reduced the IR injury. Our in vivo and in vitro investigations substantiated that IR-EVs facilitated M1-like polarization of macrophages with increased expression of proinflammatory cytokines. Further, we disclosed the miRNA profile in cardiac EVs and confirmed the enrichment of miRNAs, such as miR-155-5p in IR-EVs compared to EVs from the sham heart (S-EVs). In particular, IR-EVs transferred miR-155-5p to macrophages and enhanced the inflammatory response through activating JAK2/STAT1 pathway. Interestingly, IR-EVs not only boosted the local inflammation in the heart, but even triggered systemic inflammation in distant organs. Taken together, we newly identify an IR-EVs-miR-155-5pM1 polarization axis in the heart post IR. The EVs derived from IR-injured heart contribute to both local and systemic inflammation. Importantly, EV inhibition by GW4869 is supposed to be a promising therapeutic strategy for IR injury.
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http://dx.doi.org/10.1002/jev2.12072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902529PMC
February 2021

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats.

Front Pharmacol 2020 14;11:600953. Epub 2021 Jan 14.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.
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http://dx.doi.org/10.3389/fphar.2020.600953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841406PMC
January 2021

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients.

Front Immunol 2020 8;11:602395. Epub 2021 Jan 8.

Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The widespread prevalence of coronavirus disease-2019 (COVID-19) which is caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in a severe global public health emergency. However, there are no sensitive biomarkers to predict the disease prognosis of COVID-19 patients. Here, we have identified interleukin-8 (IL-8) as a biomarker candidate to predict different disease severity and prognosis of COVID-19 patients. While serum IL-6 become obviously elevated in severe COVID-19 patients, serum IL-8 was easily detectible in COVID-19 patients with mild syndromes. Furthermore, lL-8 levels correlated better than IL-6 levels with the overall clinical disease scores at different stages of the same COVID-19 patients. Thus, our studies suggest that IL-6 and IL-8 can be respectively used as biomarkers for severe COVID-19 patients and for COVID-19 disease prognosis.
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http://dx.doi.org/10.3389/fimmu.2020.602395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820901PMC
February 2021

miR-301a-PTEN-AKT Signaling Induces Cardiomyocyte Proliferation and Promotes Cardiac Repair Post-MI.

Mol Ther Nucleic Acids 2020 Dec 29;22:251-262. Epub 2020 Aug 29.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.

Adult hearts are hard to recover after cardiac injury due to the limited proliferative ability of cardiomyocytes. Emerging evidence indicates the induction of cell cycle reentry of cardiomyocytes by special treatment or stimulation, which offers adult heart regenerative potential. Herein, a microRNA (miRNA) screening in cardiomyocytes identified miR-301a enriched specially in the neonatal cardiomyocytes from rats and mice. Overexpression of miR-301a in primary neonatal cardiomyocytes and H9C2 cells induced G/S transition of the cell cycle, promoted cellular proliferation, and protected cardiomyocytes against hypoxia-induced apoptosis. Adeno-associated virus (AAV)9-mediated cardiac delivery of miR-301a to the mice model with myocardial infarction (MI) dramatically promoted cardiac repair post-MI . Phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was confirmed to mediate miR-301a-induced cell proliferation in cardiomyocytes. Loss of function of PTEN mimicked the miR-301a-induced phenotype, while gain of function of PTEN attenuated the miR-301a-induced cell proliferation in cardiomyocytes. Application of RG7440, a small molecule inhibitor of AKT, blocked the function of miR-301a in cardiomyocytes. The current study revealed a miRNA signaling in inducing the cell cycle reentry of cardiomyocytes in the injured heart, and it demonstrated the miR-301a/PTEN/AKT signaling as a potential therapeutic target to reconstitute lost cardiomyocytes in mammals.
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http://dx.doi.org/10.1016/j.omtn.2020.08.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515978PMC
December 2020

CD40 induces an antimicrobial response against the intracellular pathogen Streptococcus agalactiae in Nile tilapia, Oreochromis niloticus.

J Fish Dis 2021 Jan 21;44(1):45-52. Epub 2020 Sep 21.

Shenzhen Institute of Guangdong Ocean University, Shenzhen, Guangdong, China.

Streptococcus agalactiae is a Gram-positive facultative intracellular bacterium that leads to severe economic loss of tilapia worldwide. Previous studies demonstrated that CD40 contributes to host protection against intracellular injection. In this study, CD40 was characterized from Nile tilapia (Oreochromis niloticus), named OnCD40. Sequence analysis showed that open reading frame of OnCD40 was 933 bp, containing a single peptide, a transmembrane domain and four cysteine-rich domains. The qRT-PCR revealed that OnCD40 was expressed in all examined tissues with the most abundant ones in spleen and thymus. After S. agalactiae stimulation, the expression of OnCD40 was significantly induced in most of the detected organs. Moreover, OnCD40-overexpressing fish elicited significant protection against subsequent S. agalactiae challenge; approximately 10000-fold fewer bacteria were detected in spleen of OnCD40-overexpressing fish in comparison with control fish. Thus, CD40 had protecting function in Nile tilapia against intracellular pathogens.
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http://dx.doi.org/10.1111/jfd.13266DOI Listing
January 2021

Ubiquitin-like protein FAT10 promotes osteosarcoma glycolysis and growth by upregulating PFKFB3 via stabilization of EGFR.

Am J Cancer Res 2020 1;10(7):2066-2082. Epub 2020 Jul 1.

Department of Orthopedics, Second Affiliated Hospital of Nanchang University Nanchang, China.

Osteosarcoma is a major cause of cancer-related deaths in adolescents. While it thrives in a state of malnutrition, the mechanism of metabolic stress adaptation via metabolic reprogramming is unclear. Here, we found that the level of FAT10, a ubiquitin-like protein, was significantly higher in tumors than in adjacent normal tissues. Moreover, high FAT10 levels were closely related to increased malignancy and shorter survival time in osteosarcoma patients. Multivariate analysis also showed that FAT10 overexpression was an independent predictor of poor prognosis. Functional assays indicated that FAT10 promoted osteosarcoma cell proliferation by inducing glycolysis. In addition, FAT10 knockdown reduced the level of PFKFB3, a positive regulator of glycolysis in many cancers. A positive correlation was found between FAT10 and PFKFB3 levels in osteosarcoma tissues, further indicating that FAT10 induced an increase in glycolysis and that cell growth depended on PFKFB3. Interestingly, FAT10 regulated PFKFB3 expression by directly binding to EGFR and inhibiting its ubiquitination and degradation. These results shed light on the mechanisms responsible for osteosarcoma cell survival in the malnourished tumor microenvironment. Further, the results provide insights into the role of FAT10 in the adaptation of osteosarcoma cells to metabolic stress.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407346PMC
July 2020

Effects of Probiotics on Patients with Hypertension: a Systematic Review and Meta-Analysis.

Curr Hypertens Rep 2020 03 21;22(5):34. Epub 2020 Mar 21.

School of Medicine, Griffith University, Parkland Drive, Gold Coast, QLD, 4222, Australia.

Purpose Of Review: This meta-analysis and systematic review was conducted to evaluate the effect of probiotics on blood pressure, body mass index (BMI), and blood glucose changes in patients with hypertension.

Recent Findings: We searched the PubMed, Cochrane, Embase, and ProQuest databases using a combination of MeSH and free text, from the inception of these databases to 20 January 2020, with no language restrictions. The quantitative PEDro scale method was used to assess the quality of the included studies. We used the random effects models to estimate the outcomes, with heterogeneity among the studies assessed using Cochran's Q statistic. Fourteen included studies published between 2002 and 2019 were included in the meta-analysis, reporting results of 846 hypertension participants. A significant reduction in SBP by - 2.05 mmHg (95% CI - 3.87, -0.24, P = 0.03), DBP by - 1.26 mmHg (95% CI - 2.51, - 0.004, P = 0.047), BMI by - 1.03 (95% CI - 1.28, - 0.97, P < 0.01), and blood glucose by - 0.18 mmol/L (95% CI - 0.30 - 0.05, P = 0.007) was observed following probiotics intervention. Our meta-analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension, particularly in those with diabetes mellitus, following probiotic supplementation. This effect was associated with treatment duration, dosage, and the age of subject but was not associated with single or multiple strains usage. Additionally, probiotic supplement had a beneficial effect in reducing BMI and blood glucose.
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http://dx.doi.org/10.1007/s11906-020-01042-4DOI Listing
March 2020

miR-155-5p inhibition rejuvenates aged mesenchymal stem cells and enhances cardioprotection following infarction.

Aging Cell 2020 04 20;19(4):e13128. Epub 2020 Mar 20.

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.

Aging impairs the functions of human mesenchymal stem cells (MSCs), thereby severely reducing their beneficial effects on myocardial infarction (MI). MicroRNAs (miRNAs) play crucial roles in regulating the senescence of MSCs; however, the underlying mechanisms remain unclear. Here, we investigated the significance of miR-155-5p in regulating MSC senescence and whether inhibition of miR-155-5p could rejuvenate aged MSCs (AMSCs) to enhance their therapeutic efficacy for MI. Young MSCs (YMSCs) and AMSCs were isolated from young and aged donors, respectively. The cellular senescence of MSCs was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. Compared with YMSCs, AMSCs exhibited increased cellular senescence as evidenced by increased SA-β-gal activity and decreased proliferative capacity and paracrine effects. The expression of miR-155-5p was much higher in both serum and MSCs from aged donors than young donors. Upregulation of miR-155-5p in YMSCs led to increased cellular senescence, whereas downregulation of miR-155-5p decreased AMSC senescence. Mechanistically, miR-155-5p inhibited mitochondrial fission and increased mitochondrial fusion in MSCs via the AMPK signaling pathway, thereby resulting in cellular senescence by repressing the expression of Cab39. These effects were partially reversed by treatment with AMPK activator or mitofusin2-specific siRNA (Mfn2-siRNA). By enhancing angiogenesis and promoting cell survival, transplantation of anti-miR-155-5p-AMSCs led to improved cardiac function in an aged mouse model of MI compared with transplantation of AMSCs. In summary, our study shows that miR-155-5p mediates MSC senescence by regulating the Cab39/AMPK signaling pathway and miR-155-5p is a novel target to rejuvenate AMSCs and enhance their cardioprotective effects.
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http://dx.doi.org/10.1111/acel.13128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189985PMC
April 2020

Ginsenoside Rg1 protects against cigarette smoke-induced airway remodeling by suppressing the TGF-β1/Smad3 signaling pathway.

Am J Transl Res 2020 15;12(2):493-506. Epub 2020 Feb 15.

Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine 150 Jimo Road, Shanghai 200120, China.

Chronic obstructive pulmonary disease (COPD) is a devastating and common respiratory disease characterized by chronic inflammation and progressive airway remodeling. Ginsenoside Rg1 (GRg1), a major active component of , has been found to possess beneficial properties against acute lung injury and respiratory diseases. However, the effects of GRg1 on airway remodeling in COPD remain unclear. In this study, we aimed to investigate the potential protective effects of GRg1 on airway remodeling induced by cigarette smoke (CS) and the underlying mechanism. A rat model of COPD was established in which the animals were subjected to CS and GRg1 daily for 12 weeks. Subsequently, we evaluated lung function, inflammatory responses, along with airway remodeling and associated signaling factors. GRg1 treatment was found to improve pulmonary function, reduce airway collagen volume fraction, and markedly reduce the expression of IL-6, TNF-α, α-SMA, and collagen I. Moreover, GRg1 treatment decreased the expression of TGF-β1, TGF-βR1, and phosphorylated-Smad3. , pretreatment of MRC5 human lung fibroblasts with GRg1 prior to exposure to cigarette smoke extract (CSE) reversed the cell ultrastructure disorder, decreased the expression of IL-6 and TNF-α, and significantly attenuated transdifferentiation of MRC5 cells by suppressing α-SMA and collagen I expression. Additionally, GRg1 suppressed the TGF-β1/Smad3 signaling pathway in CSE-stimulated MRC5 cells, whereas Smad3 over-expression abolished the anti-transdifferentiation effect of GRg1. In conclusion, the results of our study demonstrated that GRg1 improves lung function and protects against CS-induced airway remodeling, in part by down-regulating the TGF-β1/Smad3 signaling pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061821PMC
February 2020

A comprehensive model of NO emissions in an anaerobic/oxygen-limited aerobic process under dynamic conditions.

Bioprocess Biosyst Eng 2020 Jun 12;43(6):1093-1104. Epub 2020 Mar 12.

School of Environment and Energy, South China University of Technology, 382 Zhonghuan Road East, Panyu District, Guangzhou Higher Education Mega Centre, Guangzhou, 510006, People's Republic of China.

A comprehensive model for nitrous oxide (NO) emissions in an anaerobic/oxygen-limited aerobic (A/OLA) process is proposed here. This paper includes the following main innovations: (i) adding the phosphorus-accumulating organism (X) denitrification pathway to the contribution of NO emissions; (ii) considering the biological removal of organic matter and phosphorus and predicting the effect of influent phosphorus concentration on NO emissions via an increase in the influent phosphorus concentration; and (iii) determining the effect of X on NO production in a simultaneous nitrification, denitrification and phosphorus removal (SNDPR) system by sensitivity analysis. The results suggested that the simulated data matched the measured data well. The predominant pathways of NO emissions in the process of A/OLA were the ammonium-oxidizing bacterium (X) denitrification pathway and the heterotrophic bacterium (X) denitrification pathway, while the incomplete hydroxylamine (NHOH) oxidation pathway and the X denitrification pathway contributed less to NO emissions. The metabolic activity of X had a significant effect on NO emissions, and increasing the influent phosphorus concentration was beneficial for reducing the release of NO. This study is expected to provide a meaningful reference for reducing NO emissions in wastewater treatment engineering.
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http://dx.doi.org/10.1007/s00449-020-02307-7DOI Listing
June 2020

Predictive Value of Uric Acid Regarding Cardiometabolic Disease in a Community-Dwelling Older Population in Shanghai: A Cohort Study.

Front Med (Lausanne) 2020 5;7:24. Epub 2020 Feb 5.

Shanghai East Hospital, Tongji University, Shanghai, China.

This study aimed to test the predictive power of serum uric acid (UA) levels on new-onset cardiometabolic risk in the Chinese population. Older people who visited a community health center for a yearly health check ( = 5,000; men: 47%, women: 53%) were enrolled. Participants were followed for 4 years from baseline (median: 48 months), with the endpoints being development of heart failure, atrial fibrillation, diabetes, hypertension, metabolic syndrome, or kidney disease. During follow-up, 342 men (7.4%) and 360 women (8.6%) developed hypertension; 98 men (2.48%) and 135 women (3.06%) developed diabetes; and 175 men (5.04%) and 214 women (4.51%) developed metabolic syndrome. Incident diabetes, hypertension, and metabolic syndrome increased with increased UA levels at baseline ( < 0.001). A multivariate Cox proportional hazards analysis revealed a significant, independent association between the baseline UA level and the onset and future hypertension and/or diabetes in both men and women. However, UA is associated with the development of metabolic syndrome in men, but not in women. UA is an independent predictor of new-onset diabetes and hypertension in both women and men and a predictor of new-onset metabolic syndrome only in men.
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http://dx.doi.org/10.3389/fmed.2020.00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025523PMC
February 2020

Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction.

Cardiovasc Res 2021 Jan;117(2):585-599

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong New District, Shanghai 200120, China.

Aims : Endothelial cell (EC) homoeostasis plays an important role in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodelling after myocardial infarction (MI). It has been shown that the sphingosine 1-phosphate receptor 1 (S1pr1) was highly expressed in ECs and played an important role in maintaining endothelial functions. We thus hypothesized that the endothelial S1pr1 might be involved in post-MI cardiac remodelling.

Methods And Results : Our study showed that the specific loss of endothelial S1pr1 exacerbated post-MI cardiac remodelling and worsened cardiac dysfunction. We found that the loss of endothelial S1pr1 significantly reduced Ly6clow macrophage accumulation, which is critical for the resolution of inflammation and cardiac healing following MI. The reduced reparative macrophages in post-MI myocardium contributed to the detrimental effects of endothelial S1pr1 deficiency on post-MI cardiac remodelling. Further investigations showed that the loss of endothelial S1pr1-reduced Ly6clow macrophage proliferation, while the pharmacological activation of S1pr1-enhanced Ly6clow macrophage proliferation, thereby ameliorated cardiac remodelling after MI. A mechanism study showed that S1P/S1pr1 activated the ERK signalling pathway and enhanced colony-stimulating factor 1 (CSF1) expression, which promoted Ly6clow macrophage proliferation in a cell-contact manner. The blockade of CSF1 signalling reversed the enhancing effect of S1pr1 activation on Ly6clow macrophage proliferation and worsened post-MI cardiac remodelling.

Conclusion : This study reveals that cardiac microvascular endothelium promotes reparative macrophage proliferation in injured hearts via the S1P/S1PR1/ERK/CSF1 pathway and thus ameliorates post-MI adverse cardiac remodelling.
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http://dx.doi.org/10.1093/cvr/cvaa046DOI Listing
January 2021

Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride.

Acta Pharm 2020 Sep;70(3):411-422

Affiliated Hospital,Inner Mongolia Medical University, Hohhot 010050 China.

Donepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer's disease due to its higher bioavailability and better distribution to brain when compared to oral route.
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http://dx.doi.org/10.2478/acph-2020-0032DOI Listing
September 2020

Occurrence and risk assessment of antibiotics in multifunctional reservoirs in Dongguan, China.

Environ Sci Pollut Res Int 2020 Apr 6;27(12):13565-13574. Epub 2020 Feb 6.

College of Environment and Energy, South China University of Technology, Guangzhou, 510006, Guangdong, China.

It is necessary to study the contamination of antibiotics in natural water bodies and assess its impact on ecological and human risks because of the large-scale use in the world. The occurrence and distribution characteristics of 45 antibiotics in reservoirs in Dongguan were investigated. Approximately, 77.8% of the detectable concentration of 35 antibiotics were found in the evaluation samples with concentration ranged from not detected (ND) to 729.59 ng/L, and dehydrated erythromycin was the highest one that appeared in Tongsha Reservoir. Fluoroquinolones and tetracyclines were the most abundant antibiotics with the detection frequency of 100% at sum concentration of 7.23-212.43 ng/L and 13.46-72.66 ng/L, respectively. Macrolides had a lower detected frequency but with highest concentration level at five kinds of antibiotics. Sulfamethoxazole, lincomycin, dehydrated erythromycin, pefloxacin, and panofloxacin were selected as important evaluation indicators. Sulfaguanidine, sulfamethoxazole, sulfisoxazole, dehydrated erythromycin, and clarithromycin that showed a significant correlation with Cl and SO indicated that the pollution source of these antibiotics may be related to wastewater treatment plants. Among detected antibiotics, trimethoprim, norfloxacin, sarafloxacin, lincomycin, oxytetracycline, novobiocin, dehydrated erythromycin, and clarithromycin presented high risk to aquatic ecosystem in the reservoirs. There was no risk to humans at different ages of detected antibiotics, but it should attract attention because of the cumulative effects of antibiotics, which may cause potential risks to the human body.
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http://dx.doi.org/10.1007/s11356-019-07436-5DOI Listing
April 2020

Cardio-renal Exosomes in Myocardial Infarction Serum Regulate Proangiogenic Paracrine Signaling in Adipose Mesenchymal Stem Cells.

Theranostics 2020 1;10(3):1060-1073. Epub 2020 Jan 1.

Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration. However, the molecular mechanisms underlying MSCs activation remain largely unknown, thus hindering their clinical translation. Exosomes are small vesicles that act as intercellular messengers, and their potential for stem cell activation in pathological conditions has not been fully characterized yet. Here, we aim to investigate whether serum exosomes are involved in the remote activation of MSCs after myocardial infarction (MI). We established MI mouse model by ligating the left anterior descending branch of the coronary artery. Afterwards, serum exosomes were isolated from control (Con Exo) and MI mice (MI Exo) by differential centrifugation. Exosomes were characterized through transmission electron microscopy and nanoparticle tracking analysis. The cell proliferation rate was evaluated by CCK-8 and EdU incorporation assays. Exosomal miRNA and protein levels were assessed using qRT-PCR and western blotting, respectively. VEGF levels in the supernatant and serum were quantified by ELISA. Matrigel plug and tube formation assays were used to evaluate angiogenesis. To explore miR-1956 roles, overexpression and knock-down experiments were performed using mimic and inhibitor, respectively. Finally, miR-1956 target genes were confirmed using the luciferase reporter assay. Both types of exosomes exhibited typical characteristics and could be internalized by adipose-derived MSCs (ADMSCs). MI Exo enhanced ADMSCs proliferation through the activation of ERK1/2. Gain- and loss-of-function studies allowed the validation of miR-1956 (enriched in MI Exo) as the functional messenger that stimulates ADMSCs-mediated angiogenesis and paracrine VEGF signaling, by downregulating . Finally, we found that the ischemic myocardium and kidney may be the main sources that release serum exosomes after MI. Cardio-renal exosomes deliver miR-1956 and activate paracrine proangiogenic VEGF signaling in ADMSCs after MI; this process also involves Notch-1, which functions as the core mediator.
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http://dx.doi.org/10.7150/thno.37678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956822PMC
April 2021

Removal of gentian violet and rhodamine B using banyan aerial roots after modification and mechanism studies of differential adsorption behaviors.

Environ Sci Pollut Res Int 2020 Mar 8;27(9):9152-9166. Epub 2020 Jan 8.

School of Environment and Energy, South China University of Technology, Guangzhou, 510006, China.

A novel adsorbent derived from banyan aerial roots was prepared via modification and employed to aqueous gentian violet (GV) and rhodamine B (RhB) removal. The surface morphology and physicochemical properties of modified banyan aerial roots (MBARs) were investigated by SEM, EDS, N adsorption/desorption, zeta potential, XRD, and FT-IR characterization experiments. Adsorption factors were tested, and the optimal conditions for GV and RhB removal were pH of 6 and 3, doses of 0.02 g and 0.03 g, and reaction time of 540 min. Adsorption isotherm simulation illustrated that theoretical monolayer adsorption capacities of GV and RhB were 456.64 mg/g and 115.23 mg/g, respectively. Kinetics data was assessed with pseudo-first-order and pseudo-second-order models, and the latter described GV and RhB adsorption better at 288 K, 298 K, 308 K, and 318 K. Thermodynamic analysis indicated that GV and RhB adsorption processes were endothermic and spontaneous. From the research results, it could be inferred that GV adsorption was mainly dominated by electrostatic interaction, while RhB adsorption might be primarily attributed to electrostatic interaction and hydrogen bonding. The study based on full utilization of waste plant fibers facilitates recycling of biomass resources, and due to simplicity, safety, and eco-friendliness of the preparation, as well as low cost and high efficiency of the application, MBARs may be potential absorbents for the treatment of dyestuff wastewater.
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http://dx.doi.org/10.1007/s11356-019-07024-7DOI Listing
March 2020

Ubiquitin-like protein FAT10 promotes osteosarcoma growth by modifying the ubiquitination and degradation of YAP1.

Exp Cell Res 2020 02 24;387(2):111804. Epub 2019 Dec 24.

Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address:

Osteosarcoma is a common malignancy of the bone tissue. The rapid growth exhibited by this cancer is a primary challenge in its treatment. In many types of cancers, FAT10, a ubiquitin-like protein, is involved in several biological activities, especially cell proliferation. Herein, we demonstrate that FAT10 plays a vital role in tumorigenesis and is overexpressed in tumor tissues compared to its expression in adjacent normal tissues. Functional assays revealed that knockdown of FAT10 expression significantly repressed the proliferation of osteosarcoma in vitro and in vivo. Furthermore, our results indicate that FAT10 exhibits oncogenic functions by regulating the level of YAP1, a key protein of the Hippo/YAP signaling pathway, and a significant positive correlation exists between the levels of FAT10 and YAP1. Further analysis showed that FAT10-induced growth of osteosarcoma cells is dependent on YAP1. Mechanistically, FAT10 stabilizes YAP1 expression by regulating its ubiquitination and degradation. Taken together, our results link the two drivers of cell growth in osteosarcoma and reveal a novel pathway for FAT10 regulation. We provide new evidence for the biological and clinical significance of FAT10 as a potential biomarker for osteosarcoma.
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http://dx.doi.org/10.1016/j.yexcr.2019.111804DOI Listing
February 2020

Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway.

J Cell Mol Med 2020 01 19;24(2):2013-2026. Epub 2019 Dec 19.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1-phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post-TAC hearts. Endothelial-specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC-S1pr1-overexpression on angiotensin II (AngII)-induced cardiomyocyte (CM) hypertrophy, as well as on TGF-β-mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC-induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC-S1pr1 might prevent the development of pressure overload-induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC-targeting S1pr1-AKT-eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.
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http://dx.doi.org/10.1111/jcmm.14900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991681PMC
January 2020

Nanocrystalline Li-Al-Mn-Si Foil as Reversible Li Host: Electronic Percolation and Electrochemical Cycling Stability.

Nano Lett 2020 Feb 20;20(2):896-904. Epub 2019 Dec 20.

Department of Nuclear Science and Engineering and Department of Materials Science and Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

When a metallic foil (Li metal or LiAl) with initial Li inventory (LiInv) is used as the anode in lithium-ion batteries, its metallurgical damage state in the presence of organic liquid electrolyte and cycling electrochemical potential is of great interest. While LiAl foil operates at a voltage that eliminates Li dendrite, the state-of-health (SOH) of LiAl anode can still degrade quickly in full-cell cycling. To analyze the causes, we decompose SOH = SOHe × SOHi × LiInv, where SOHe is SOH of electronic percolation within the anode, SOHi is SOH of Li percolation from cathode to the anode interior, and LiInv is the amount of cyclable lithium in a full cell, all normalized such that 1 means perfectly healthy, and 0 means dead. Any of the three (SOHe, SOHi, LiInv) dropping to zero would mean death of the full cell. Considering the poor performance of pure Al foil due to rapid drop in LiInv, we employed a mechanical prelithiation (MP) method to make LiInv >1 initially. The chemomechanical shock from MP creates an ultrananocrystalline LiAl layer with grain size 10-30 nm on top of unreacted Al. We then monitor SOHe evolution of the anode foil by measuring the in-plane electronic conductance . We find that small additions of Mn or Si into Al induce nanoprecipitates Zener pinning, and the resulting denser grain boundary (GB) network before MP significantly reduces foil porosity after MP, delays gross foil fracture, and improves SOHe in subsequent cycling. Microstructural analysis reveals that the refined grain size of foil before MP relieves stress and reduces the chance of forming electronically isolated dead grain cluster due to cracking and invasion of electrolyte and solid-electrolyte interphase (SEI). By maintaining good electronic percolation, binder-free LiAlMnSi anode demonstrates an order-of-magnitude more stable SOHe and better electrochemical cycling performance than LiAl anode.
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http://dx.doi.org/10.1021/acs.nanolett.9b03626DOI Listing
February 2020

Adsorption properties and mechanisms of novel biomaterials from banyan aerial roots via simple modification for ciprofloxacin removal.

Sci Total Environ 2020 Mar 21;708:134630. Epub 2019 Nov 21.

School of Environment and Energy, South China University of Technology, 382 Zhonghuan Road East, Panyu District, Guangzhou Higher Education Mega Centre, Guangzhou 510006, China.

The study investigated ciprofloxacin (CIP) adsorption capacity of the novel biomaterials prepared from banyan aerial roots by simple thermochemical modification. Pretreated banyan aerial root fibers were modified with a green reagent citric acid (1 M) at 90, 120 and 150 °C, which enhanced the fiber adsorption capacity revealed by characterization and adsorption tests. Several characterization methods were applied to exploring the surface morphologies and physicochemical properties of unmodified banyan aerial roots (UBARs) and modified banyan aerial roots (T-MBARs, T stands for the modification temperature). Based on SEM images and N adsorption/desorption isotherms, the modification resulted in decrease of the specific surface area owing to cellulose molecular linking. In that case, the improved CIP adsorption of MBARs might be attributed to the larger carboxyl quantity and stronger electronegativity manifested via FTIR spectra and zeta potential analysis. Through the adsorption experiments, the optimal pH value of 8 and the suitable absorbent dosage of 0.03 g were obtained. The simulation results showed that the Freundlich model can fit the adsorption thermodynamic data quite well, while the kinetic data was simulated preferably by the pseudo-second-order kinetic equation signifying the chemical adsorption process, and the intra-particle diffusion was involved in the adsorption consisted of three stages. The findings of batch experiments under diverse operations represented that MBARs purified aqueous CIP better than UBARs, closely related to the superior electronegativity. Both characterization and adsorption studies illustrated the dominant role of electrostatic interaction during CIP removal, accompanied by hydrogen bonding and diffusion interaction besides. The present work suggested that MBAR fibers could possess a promising application to ciprofloxacin potent removal from aqueous solutions.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134630DOI Listing
March 2020

A novel small molecule compound VCP979 improves ventricular remodeling in murine models of myocardial ischemia/reperfusion injury.

Int J Mol Med 2020 Feb 27;45(2):353-364. Epub 2019 Nov 27.

Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VCP979, a novel small‑molecule compound developed in‑house, possesses anti‑inflammatory and anti‑fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VCP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro‑inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VCP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)‑induced collagen synthesis and neonatal cardiac myocytes (NCMs) hypertrophy. In addition, VCP979 attenuated the activation of p38‑mitogen‑activated protein kinase in both Ang II‑induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small‑molecule compound VCP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.
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http://dx.doi.org/10.3892/ijmm.2019.4413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984775PMC
February 2020

Distinct Circulating Expression Profiles of Long Noncoding RNAs in Heart Failure Patients With Ischemic and Nonischemic Dilated Cardiomyopathy.

Front Genet 2019 12;10:1116. Epub 2019 Nov 12.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.
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http://dx.doi.org/10.3389/fgene.2019.01116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861296PMC
November 2019

AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling Inhibiting PDGFR and STAT Pathway.

Front Pharmacol 2019 15;10:1142. Epub 2019 Oct 15.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling . Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R.
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http://dx.doi.org/10.3389/fphar.2019.01142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803464PMC
October 2019

Circular RNA expression alterations in extracellular vesicles isolated from murine heart post ischemia/reperfusion injury.

Int J Cardiol 2019 12 14;296:136-140. Epub 2019 Aug 14.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China; Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China; Institute of Integrated Traditional Chinese and Western Medicine for Cardiovascular Chronic Diseases, Tongji University School of Medicine, Shanghai 200120, PR China. Electronic address:

Background: Increasing studies indicated the involvement of extracellular vesicles (EVs) in cardiovascular diseases. However, the role of circular RNAs (circRNAs) in cardiac EVs (cEVs) during ischemia/reperfusion (I/R) injury remain unclear.

Methods: We isolated the cEVs from I/R injured hearts and performed RNA sequencing (RNA-seq) to identify the profile of circRNA in cEVs and investigated their potential roles in I/R pathological process.

Results: Cardiac I/R induced a significantly elevated release of EVs in heart within 24 h. RNA-seq of cEVs identified 185 significantly differentially expressed (DE) circRNAs including 119 down-regulated and 66 up-regulated circRNAs in I/R group compared with the sham. GO and pathway analysis showed that these DE-circRNAs were associated with protein binding and kinase activator activity and mainly involved in the metabolic process. The circRNA-miRNA analysis exhibited the broad potentials of the DE-circRNAs to regulate target genes by acting on the miRNAs.

Conclusions: These findings revealed for the first time the specific expression pattern of circRNAs in EVs derived from sham and I/R heart tissues and provided some potential targets and pathways involving in I/R injury which may provide important evidences for the role of both circRNA and EVs in the pathology of cardiac I/R.
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http://dx.doi.org/10.1016/j.ijcard.2019.08.024DOI Listing
December 2019

Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B.

J Viral Hepat 2019 07;26 Suppl 1:77-84

Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.

Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother-to-child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3-17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)-IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG-IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG-IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG-IFNa-treated CHB adults. Further analysis revealed that younger children (3-6 years old) were more responsive to PEG-IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10-17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG-IFNa-mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.
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http://dx.doi.org/10.1111/jvh.13165DOI Listing
July 2019

The Gut Microbial Metabolite Trimethylamine N-Oxide and Hypertension Risk: A Systematic Review and Dose-Response Meta-analysis.

Adv Nutr 2020 01;11(1):66-76

Institute of Integrated Traditional Chinese and Western Medicine for Cardiovascular Chronic Diseases, Tongji University School of Medicine, Shanghai, People's Republic of China.

The gut microbial metabolite trimethylamine N-oxide (TMAO) is increasingly regarded as a novel risk factor for cardiovascular events and mortality. However, little is known about the association between TMAO and hypertension. This meta-analysis was conducted to quantitatively assess the relation between the circulating TMAO concentration and hypertension prevalence. The PubMed, Cochrane Library, and Embase databases were systematically searched up to 17 June 2018. Studies recording the hypertension prevalence in members of a given population and their circulating TMAO concentrations were included. A total of 8 studies with 11,750 individuals and 6176 hypertensive cases were included in the analytic synthesis. Compared with low circulating TMAO concentrations, high TMAO concentrations were correlated with a higher prevalence of hypertension (RR: 1.12; 95% CI: 1.06, 1.17; P < 0.0001; I2 = 64%; P-heterogeneity = 0.007; random-effects model). Consistent results were obtained in all examined subgroups as well as in the sensitivity analysis. The RR for hypertension prevalence increased by 9% per 5-μmol/L increment (RR: 1.09; 95% CI: 1.05, 1.14; P < 0.0001) and 20% per 10-μmol/L increment of circulating TMAO concentration (RR: 1.20; 95% CI: 1.11, 1.30; P < 0.0001) according to the dose-response meta-analysis. To our knowledge, this is the first systematic review and meta-analysis demonstrating a significant positive dose-dependent association between circulating TMAO concentrations and hypertension risk.
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http://dx.doi.org/10.1093/advances/nmz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442397PMC
January 2020

Dynamic Profile of CD4 T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion.

Mediators Inflamm 2019 18;2019:9483647. Epub 2019 Mar 18.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200092, China.

CD4 T-cells play crucial roles in the injured heart. However, the way in which different CD4 T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4 subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4 T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1, MCP-3, and GRO- were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1, MCP-3, and GRO- increased in both injured heart tissues and serum, while IFN-, IL-12P70, IL-2, IL-1, IL-18, TNF-, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-, IL-12P70, IL-2, IL-18, TNF-, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO- were reduced, while IL-1 and MIP-2 were elevated at day 14. IL-13 and MIP-1 showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1, MCP-3, and GRO- mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4 T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.
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http://dx.doi.org/10.1155/2019/9483647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442492PMC
August 2019

Full-Cell Cycling of a Self-Supporting Aluminum Foil Anode with a Phosphate Conversion Coating.

ACS Appl Mater Interfaces 2019 May 22;11(17):15656-15661. Epub 2019 Apr 22.

Department of Nuclear Science and Engineering and Department of Materials Science and Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

Aluminum foil is a promising candidate anode material for lithium-ion batteries (LIBs), due to its high theoretical capacity, low lithiation voltage, and abundance. However, as a matter of fact, it has been a great challenge to make Al foil cycle in full cells at industrially acceptable areal capacities of 2-4 mAh/cm for commercial 18650 LIBs and some high-power LIBs. In this study, we defined the concepts of electrochemical true contact area (ECA) (areas with perfect electrolyte/electrode contact) and electrochemical noncontact area (ENA) (referred to regions without electrolyte spread on) for the metal foil anode. An initial ECA/ENA partition would cause severe inhomogeneity of the alloying reaction, cause localized electrode pulverization, and exacerbate ECA/ENA inequality even more. Through a phosphate conversion coating on aluminum foil, we killed two birds with one stone: first, the Al foil with a phosphate conversion coating has improved wettability (characterized by the contact angle that decreased from 35.2 to 15.9°) and favors the elimination of ENA, thus guaranteeing uniform electrochemical contact; also, the coating functions as an artificial solid electrolyte interface, which stabilizes the fragile naturally formed solid electrolyte interface and a "steady-state" electrolyte/electrode interface. Therefore, when pairing the phosphated Al foil anode against a commercial LiFePO (LFP) cathode (with ∼2.65 mAh/cm), it can cycle 120 times without Li excess and stabilizes at 1.27 mAh/cm.
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http://dx.doi.org/10.1021/acsami.9b02813DOI Listing
May 2019

Gut microbe-generated metabolite trimethylamine N-oxide and the risk of diabetes: A systematic review and dose-response meta-analysis.

Obes Rev 2019 06 13;20(6):883-894. Epub 2019 Mar 13.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Elevated circulating concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) were found in patients with type 2 diabetes mellitus (T2DM). However, whether a high level of TMAO is related to the risk of diabetes has not been studied. We aimed to synthesize the evidence on the relation between TMAO levels and the risk of diabetes mellitus (DM) and to investigate the association further in a dose-response meta-analysis. PubMed, Web of Science, and Scopus databases were searched for studies from inception to June 2018. A total of 12 clinical studies were included in this study, and 15 314 enrolled subjects were included. A meta-analysis of two-class variables and continuous variables were used to obtain pooled effects. Dose-response meta-analysis was used to investigate the dose-response relationship between TMAO concentrations and the risk of DM. Meta-regression and subgroup analyses were applied to identify the source of heterogeneity in this study. High levels of circulating TMAO were associated with an increased risk of DM (odds ratio [OR] = 1.89) using the two-class meta-analysis. Plasma levels of TMAO in patients with diabetes were higher than in subjects without diabetes (standardized mean difference [SMD]: 0.36) using a meta-analysis of continuous variables. The OR for DM prevalence increased by 54% per 5 μmol L increment of plasma TMAO (OR = 1.54) according to the dose-response meta-analysis. This is the first systematic review and meta-analysis to demonstrate a positive dose-dependent association between circulating TMAO levels and increased diabetes risk.
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http://dx.doi.org/10.1111/obr.12843DOI Listing
June 2019