Publications by authors named "Shiyao Zhang"

29 Publications

  • Page 1 of 1

Study on the Baseline Factors and Platelet Indices That Predict Outcome of Acute Ischemic Stroke Patients after Thrombolytic Therapy.

Cerebrovasc Dis 2021 Nov 17:1-8. Epub 2021 Nov 17.

Department of Neurology, Nanjing Lishui People's Hospital, ZhongDa Hospital Lishui Branch, Southeast University, Nanjing, China.

Background: The aim of the study was to investigate the baseline characters that influence 3-month clinical outcomes in patients with acute ischemic stroke (AIS) after thrombolytic therapy.

Methods: We consecutively enrolled 241 AIS patients who are treated with thrombolytic therapy with recombinant tissue plasminogen activator. Baseline characters were measured on admission including the National Institutes of Health Stroke Scale (NIHSS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), risk factors, platelet indices, and lipid parameters. The subjects were divided into good or poor functional outcomes based on modified Rankin Scale at 3 months. The multivariate logistic regression was performed to explore the association between baseline factors and outcomes. Pearson correlation was used to investigate whether linear associations existed between platelet indices in different outcomes.

Results: Multivariate logistic regression analysis showed that the NIHSS, TOAST classification, diabetes, mean platelet volume (MPV) are important factors for predicting clinical outcomes after 3 months in AIS patients. We found a correlation between elevated MPV and worse outcome at 3 months, particularly in large-artery atherosclerosis stroke patients. MPV and platelet count are negative correlated (r = -0.375, p = 0.000). MPV and platelet-to-lymphocyte ratio (PLR) (r = 0.83, p = 0.000), MPV and platelet distribution width (PDW) (r = 0.820, p = 0.000) both have highly positive linear correlations in patients with good outcome.

Conclusions: Overall, lower NIHSS and MPV levels on admission were predictors of good functional outcomes in patients with AIS after undergoing thrombolytic therapy. The correlations between MPV, PDW, and PLR may be helpful to evaluate prognosis in stroke patients and deserve further exploration.
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http://dx.doi.org/10.1159/000519705DOI Listing
November 2021

Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis.

Front Oncol 2021 15;11:744064. Epub 2021 Oct 15.

Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The landscape of intratumor heterogeneity (ITH) is present from the tumor evolution. ITH is a promising clinical indicator, but the association between ITH and prognosis remains controversial. Therefore, a meta-analysis was performed to explore whether ITH can serve as a valuable prognostic indicator in solid tumors.

Methods: All included studies were from PubMed, Embase, Cochrane, and Web of Science databases up to October 10, 2020. Studies based on ITH with available prognostic information were included. Three researchers independently completed study selection and data extraction following PRISMA guidelines. The random-effect model was used for synthesis. Hazard ratio (HR) and 95% confidence intervals (CI) were used with the endpoint defined by overall survival (OS), disease-specific survival (DFS), and progression-free survival (PFS).

Results: A total of 9,804 solid tumor patients from 21 studies were included. Analysis of specific cancers in the TCGA database showed similar results based on different ITH assessment methods, which provided the logical support for data consolidation. Available evidence revealed a negative relationship between ITH and prognosis for a specific cancer (such as lung cancer). However, the OS results from 14 tumor types showed that high ITH associated with shorter survival time [HR 1.65 (95% CI, 1.42-1.91)]. PFS and DFS analyses showed similar results [HR 1.89 (95% CI, 1.41-2.54) and HR 1.87 (95% CI, 1.15-3.04)] in general. The status of tumor metastasis and sampling models were not the confounding factors.

Conclusions: High ITH is associated with worse prognosis in many solid tumors in general although this association was absent for some cancers. ITH is expected to be a promising clinical prognostic factor for the improvement of assessment, treatment, and surveillance strategy.
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http://dx.doi.org/10.3389/fonc.2021.744064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554141PMC
October 2021

MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice.

Biomaterials 2021 11 11;278:121183. Epub 2021 Oct 11.

State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121183DOI Listing
November 2021

Green light exposure aggravates high-fat diet feeding-induced hepatic steatosis and pancreatic dysfunction in male mice.

Ecotoxicol Environ Saf 2021 Dec 20;225:112802. Epub 2021 Sep 20.

State Key Laboratory of Natural Medicines, School of Life Science and Technology and Experimental Platform for Drug Chronological Intervention and Therapy, China Pharmaceutical University, Nanjing, Jiangsu, China; Key Laboratory of Active Components of Natural Medicine and Drug Release Technology, School of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address:

The increased incidence of metabolic syndrome (MetS) has been demonstrated to be closely associated with external environments, such as unhealthy ambient light exposure. Of note, spectral distribution of the light functions as a critical determinant of light's pathophysiological effects. However, the effects of the lighting spectrum on metabolic homeostasis and the specific target organs remain elusive. To address this concern, we in this study high-fat diet (HFD)-fed obese mice with different spectra of the light, and divided them into white light (WL)-treated group, green light (GL)-treated group and blue light (BL)-treated group. We found that compared with BL- or WL-treated obese mice, animals exposed to GL showed worsened metabolic status, including increased body weight gain, impaired glucose tolerance/insulin sensitivity, increased levels of serum lipids, and decreased levels of serum insulin. At the organ level, GL exposure particularly exacerbated hepatic lipid accumulation and enlarged the islet volume. Taking advantages of metabolomics and transcriptomics analyses, we screened out taurocholic acid (TCA) and adenosine (AD) as two promising metabolites mediating the deleterious effects of GL on the liver and islets, respectively. In detail, GL aggravates HFD-induced lipid synthesis and gluconeogenesis in the liver via the reduction of TCA, while triggering inflammation and cellular dysfunction in islets via the induction of AD. Collectively, our findings confirmed that GL and the HFD have a synergistic effect in the induction of metabolic disorders. DATA AVAILABILITY: All data supported the paper are present in the paper and/or the Supplementary Materials. The original datasets are also available from the corresponding author upon request.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112802DOI Listing
December 2021

Host Gasdermin D restrains systemic endotoxemia by capturing Proteobacteria in the colon of high-fat diet-feeding mice.

Gut Microbes 2021 Jan-Dec;13(1):1946369

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Gasdermin D (GSDMD) functions as a key pyroptotic executor through its secreted N-terminal domain (GSDMD-N). However, the functional relevance and mechanistic basis of the precise roles of host colonic GSDMD in high-fat diet (HFD)-induced gut dysbiosis and systemic endotoxemia remain elusive. In this study, we demonstrate that HFD feeding triggers GSDMD-N secretion of both T-lymphocytes and enterocytes in mouse colons. GSDMD deficiency aggravates HFD-induced systemic endotoxemia, gut barrier impairment, and colonic inflammation. More importantly, active GSDMD-N kills the phylum via directly interacting with Cardiolipin. Mechanistically, we identify that the Glu236 (a known residue for GSDMD protein cleavage) is a important site for the bacterial recognition of GSDMD. Collectively, our findings explain the mechanism by which colonic GSDMD-N maintains low levels of HFD-induced metabolic endotoxemia. A GSDMD-N mimetic containing an exposed Glu236 site could be an attractive strategy for the treatment of HFD-induced metabolic endotoxemia.
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http://dx.doi.org/10.1080/19490976.2021.1946369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288038PMC
July 2021

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications.

Int J Mol Sci 2021 Jun 6;22(11). Epub 2021 Jun 6.

State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.

Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.
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http://dx.doi.org/10.3390/ijms22116110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201163PMC
June 2021

Quantitative evaluation of lipid layer thickness and blinking in children with allergic conjunctivitis.

Graefes Arch Clin Exp Ophthalmol 2021 Sep 18;259(9):2795-2805. Epub 2021 May 18.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510000, Guangdong, China.

Purpose: To quantitatively evaluate the lipid layer thickness (LLT) and blinking in children with or without allergic conjunctivitis (AC), and to compare those between the different types of AC.

Methods: For this case-control study, 81 children with symptomatic AC with an average age of 9.62 ± 2.67 years were enrolled and subdivided according to the subtypes of AC, including seasonal/perennial allergic conjunctivitis group and vernal keratoconjunctivitis (VKC)/atopic keratoconjunctivitis (AKC) group. Another 82 age-matched healthy children were enrolled as control group. All subjects underwent routine eye examination and measurements of LLT, the number of incomplete or total blinking, partial blinking rate by the LipiView interferometer over a 10-s period. Other ocular surface assessment included fluorescein tear breakup time (TBUT), lower tear meniscus height, meibomian gland loss (MGL), meibum expressibility and quality.

Results: Pediatric patients with AC had significant thinner LLT, shorter TBUT, decreased total blinking but increased partial blinking rate, especially in those with VKC/AKC (all P < 0.05). A significant deterioration of meibomian gland parameters was observed in AC group when compared with control subjects, demonstrated by severe upper and lower MGL, lid margin abnormalities, decreased meibum expressibility, and abnormal meibum quality, all of which were worse in the severe type of AC (all P < 0.05). Thinner LLT was significantly correlated with decreased TBUT (β = 3.666, P < 0.001) and severity of upper MGL (β =  - 7.701, P = 0.002).

Conclusion: Decreased LLT and blinking disorders in pediatric patients with AC may contribute to lipid layer deficiency in the long run, which should be considered and appropriately diagnosed for a more precise treatment.
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http://dx.doi.org/10.1007/s00417-021-05199-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129599PMC
September 2021

[Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a].

Sheng Wu Gong Cheng Xue Bao 2021 Feb;37(2):500-512

School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu, China.

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.
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http://dx.doi.org/10.13345/j.cjb.200312DOI Listing
February 2021

Defining the mechanism of PDI interaction with disulfide-free amyloidogenic proteins: Implications for exogenous protein expression and neurodegenerative disease.

Int J Biol Macromol 2021 Mar 28;174:175-184. Epub 2021 Jan 28.

School of Life Science, Liaoning University, Shenyang 110036, China. Electronic address:

Protein disulfide isomerase (PDI) is an important molecular chaperone capable of facilitating protein folding in addition to catalyzing the formation of a disulfide bond. To better understand the distinct substrate-screening principles of Pichia pastoris PDI (Protein disulfide isomerase) and the protective role of PDI in amyloidogenic diseases, we investigated the expression abundance and intracellular retention levels of three archetypal amyloidogenic disulfide bond-free proteins (Aβ42, α-synuclein (α-Syn) and SAA1) in P. pastoris GS115 strain without and with the overexpression of PpPDI (P. pastoris PDI). Intriguingly, amyloidogenic Aβ42 and α-Syn were detected only as intracellular proteins whereas amyloidogenic SAA1 was detected both as intracellular and extracellular proteins when these proteins were expressed in the PpPDI-overexpressing GS115 strain. The binding between PpPDI and each of the three amyloidogenic proteins was investigated by molecular docking and simulations. Three different patterns of PpPDI-substrate complexes were observed, suggesting that multiple modes of binding might exist for the binding between PpPDI and its amyloidogenic protein substrates, and this could represent different specificities and affinities of PpPDI toward its substrates. Further analysis of the proteomics data and functional annotations indicated that PpPDI could eliminate the need for misfolded proteins to be partitioned in ER-associated compartments.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.172DOI Listing
March 2021

Subconjunctival injection of tumor necrosis factor-α pre-stimulated bone marrow-derived mesenchymal stem cells enhances anti-inflammation and anti-fibrosis in ocular alkali burns.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 25;259(4):929-940. Epub 2020 Nov 25.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.

Purpose: To investigate the therapeutic effect of subconjunctival injection of tumor necrosis factor-α (TNF-α) pre-stimulated bone marrow-derived mesenchymal stem cells (BMMSCs) on ocular alkali burns in a rat model.

Methods: After applying a 6 mm filter paper soaking in 1 N NaOH on the cornea of rats, the suspension of TNF-α pre-stimulated BMMSCs, BMMSCs and PBS were given subconjunctivally and respectively. Corneal epithelial defect, corneal opacity, inflammation as well as PTGS2 and TSG-6 expression on day 7 and fibrosis on day 14 were compared.

Results: TNF-α pre-stimulated BMMSCs group had a more predominate effect on promoting corneal epithelial repairing, decreasing corneal opacity, reducing inflammatory cells and CD68 + macrophages on day 7 and suppressing fibrosis on day 14 compared to BMMSCs group. Besides, it had significant increased expressions of PTGS2 and TSG-6 in vitro. Pre-treated with Indomethacin revealed a reverse effect on above-mentioned changes.

Conclusion: Subconjunctival injection of TNF-α pre-stimulated BMMSCs enhanced anti-inflammatory and anti-fibrotic effect in ocular alkali burns, which was possibly though up regulation of PTGS2 and TSG-6 expression.
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http://dx.doi.org/10.1007/s00417-020-05017-8DOI Listing
April 2021

Characterization of conjunctival microbiome dysbiosis associated with allergic conjunctivitis.

Allergy 2021 02 2;76(2):596-600. Epub 2020 Nov 2.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1111/all.14635DOI Listing
February 2021

Housing temperature affects the circadian rhythm of hepatic metabolism and clock genes.

J Endocrinol 2020 11;247(2):183-195

School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, China.

Environmental temperature remarkably impacts on metabolic homeostasis, raising a serious concern about the optimum housing temperature for translational studies. Recent studies suggested that mice should be housed slightly below their thermoneutral temperature (26°C). On the other hand, the external temperature, also known as a zeitgeber, can reset the circadian rhythm. However, whether housing temperature affects the circadian oscillators of the liver remains unknown. Therefore, we have compared the effect of two housing temperatures, namely 21°C (conventional; TC) and 26°C (thermoneutral; TN), on the circadian rhythms in mice. We found that the rhythmicity of food intake showed an advanced phase at TC, while the activity was more robust at TN, with a prolonged period onset. The serum levels of norepinephrine were remarkably induced at TC, but failed to oscillate rhythmically at both temperatures. Likewise, circulating glucose levels were increased but were non-rhythmic under TC. Both total cholesterol and triglycerides levels were induced at TN, but showed an advanced phase under TC. Additionally, the expression of hepatic metabolic genes and clock genes remained rhythmic at both temperatures, with the exception of G6Pase, Fasn, Cpt1a and Cry2, at TN. Nevertheless, the liver histology examination did not show any significant changes in response to housing temperature. Although the non-consistent trends of phase changes in each temperature, our results suggest a non-reductant role of temperature in mouse internal rhythmicity resetting. Thus, the temperature-controlled internal circadian synchronization within organs should be taken into consideration when optimizing housing temperature for mice.
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http://dx.doi.org/10.1530/JOE-20-0100DOI Listing
November 2020

Piper sarmentosum Roxb.: A review on its botany, traditional uses, phytochemistry, and pharmacological activities.

J Ethnopharmacol 2020 Dec 1;263:112897. Epub 2020 Jul 1.

Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China. Electronic address:

Ethnopharmacological Relevance: Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant widely distributed in India, Malaysia, Thailand, and the southeastern coastal areas of China including Fujian, Guangdong, and Guizhou. It has been used for centuries for the treatment of wind-cold cough, fever, rheumatism arthralgia, diarrhea dysentery, postpartum foot swelling, stomachache, toothache, diabetes, and traumatic injury.

Aims Of The Review: To critically anayze the literature for the botany, traditional uses, phytochemistry, pharmacology, toxicity, and clinical trials of P. sarmentosum in order to provide a scientific consensus for further research and discovery of potential candidate drugs.

Materials And Methods: The contents of this review were sourced from electronic databases including PubMed, SciFinder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wanfang, Chinese Scientific and Technological Periodical Database (VIP), Chinese Biomedical Database (CBM), Cochrane Controlled register of Clinical Trials, Clinical Trials. gov, and Chinese Clinical Trial Registry. Chinese medicine books published over the years were used to elucidate the traditional uses of P. sarmentosum and additional information was also collected from Yao Zhi website (https://db.yaozh.com/).

Results: Phytochemical analyses of the chemical constituents of P. sarmentosum include essential oil, alkaloids, flavonoids, lignans, and steroids. The literature supports the ethnomedicinal uses of P. sarmentosum for the treatment of cold, gastritis, and rheumatoid joint pain, and further confirms its relatively new pharmacological activities, including anti-inflammatory, antineoplastic, and antipyretic activities. Other biological roles such as anti-osteoporosis, antibacterial, antidepressant, anti-atherosclerotic, and hypoglycemic activities have also been reported. However, the methodologies employed in individual studies are limited.

Conclusions: There is convincing evidence from both in vitro and in vivo studies supporting the traditional use of P. sarmentosum and it is imperative that natural bioactive compounds are examined further. More efforts should be focused on the pharmacodynamic constituents of P. sarmentosum to provide practical basis for quality control, and additional studies are needed to understand the mechanism of their action. Further studies on the comprehensive evaluation of medicinal quality and understandings of serum chemistry, multi-target network pharmacology, and molecular docking technology of P. sarmentosum are of great importance and should be considered.
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http://dx.doi.org/10.1016/j.jep.2020.112897DOI Listing
December 2020

Endogenous circadian time genes expressions in the liver of mice under constant darkness.

BMC Genomics 2020 Mar 12;21(1):224. Epub 2020 Mar 12.

School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, China.

Background: The circadian rhythms regulate physiological functions and metabolism. Circadian Time (CT) is a unit to quantify the rhythm of endogenous circadian clock, independent of light influence. To understand the gene expression changes throughout CT, C57BL/6 J mice were maintained under constant darkness (DD) for 6 weeks, and the liver samples were collected starting at 9:00 AM (CT1), and every 4 h in a 24-h cycle (CT5, CT9, CT13, CT17 and CT21). Total RNA was extracted and subjected to RNA-Seq data (deposited as GSE 133342, L-DD). To compare gene oscillation pattern under normal light-dark condition (LD, GSE114400) and short time (2 days) dark-dark condition (S-DD, GSE70497), these data were retried from GEO database, and the trimmed mean of M-values normalization was used to normalize the three RNA-seq data followed by MetaCycle analysis.

Results: Approximate 12.1% of the genes under L-DD exhibited significant rhythmically expression. The top 5 biological processes enriched in L-DD oscillation genes were mRNA processing, aromatic compound catabolic process, mitochondrion organization, heterocycle catabolic process and cellular nitrogen compound mitotic catabolic process. The endogenous circadian rhythms of clock genes, P450 genes and lipid metabolism genes under L-DD were further compared with LD and S-DD. The oscillation patterns were similar but the period and amplitude of those oscillation genes were slightly altered. RT-qPCR confirmed the selected RNA sequence findings.

Conclusions: This is the first study to profile oscillation gene expressions under L-DD. Our data indicate that clock genes, P450 genes and lipid metabolism genes expressed rhythmically under L-DD. Light was not the necessary factor for persisting circadian rhythm but influenced the period and amplitude of oscillation genes.
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http://dx.doi.org/10.1186/s12864-020-6639-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066782PMC
March 2020

SWI/SNF complex subunit BAF60a represses hepatic ureagenesis through a crosstalk between YB-1 and PGC-1α.

Mol Metab 2020 02 20;32:85-96. Epub 2019 Dec 20.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; State key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, 211198, China. Electronic address:

Objective: Ureagenesis predominantly occurs in the liver and functions to remove ammonia, and the dysregulation of ureagenesis leads to the development of hyperammonemia. Recent studies have shown that ureagenesis is under the control of nutrient signals, but the mechanism remains elusive. Therefore, intensive investigation of the molecular mechanism underlying ureagenesis will shed some light on the pathology of metabolic diseases related to ammonia imbalance.

Methods: Mice were fasted for 24 h or fed a high-fat diet (HFD) for 16 weeks. For human evaluation, we obtained a public data set including 41 obese patients with and without hepatic steatosis. We analyzed the expression levels of hepatic BAF60a under different nutrient status. The impact of BAF60a on ureagenesis and hyperammonemia was assessed by using gain- and loss-of-function strategies. The molecular chaperons mediating the effects of BAF60a on ureagenesis were validated by molecular biological strategies.

Results: BAF60a was induced in the liver of both fasted and HFD-fed mice and was positively correlated with body mass index in obese patients. Liver-specific overexpression of BAF60a inhibited hepatic ureagenesis, leading to the increase of serum ammonia levels. Mechanistically, BAF60a repressed the transcription of Cps1, a rate-limiting enzyme, through interaction with Y-box protein 1 (YB-1) and by switching the chromatin structure of Cps1 promoter into an inhibitory state. More importantly, in response to different nutrient status, PGC-1α (as a transcriptional coactivator) and YB-1 competitively bound to BAF60a, thus selectively regulating hepatic fatty acid β-oxidation and ureagenesis.

Conclusion: The BAF60a-YB-1 axis represses hepatic ureagenesis, thereby contributing to hyperammonemia under overnutrient status. Therefore, hepatic BAF60a may be a novel therapeutic target for the treatment of overnutrient-induced urea cycle disorders and their associated diseases.
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http://dx.doi.org/10.1016/j.molmet.2019.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953711PMC
February 2020

Angptl8 mediates food-driven resetting of hepatic circadian clock in mice.

Nat Commun 2019 08 6;10(1):3518. Epub 2019 Aug 6.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, China.

Diurnal light-dark cycle resets the master clock, while timed food intake is another potent synchronizer of peripheral clocks in mammals. As the largest metabolic organ, the liver sensitively responds to the food signals and secretes hepatokines, leading to the robust regulation of metabolic and clock processes. However, it remains unknown which hepatokine mediates the food-driven resetting of the liver clock independent of the master clock. Here, we identify Angptl8 as a hepatokine that resets diurnal rhythms of hepatic clock and metabolic genes in mice. Mechanistically, the resetting function of Angptl8 is dependent on the signal relay of the membrane receptor PirB, phosphorylation of kinases and transcriptional factors, and consequently transient activation of the central clock gene Per1. Importantly, inhibition of Angptl8 signaling partially blocks food-entrained resetting of liver clock in mice. We have thus identified Angptl8 as a key regulator of the liver clock in response to food.
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http://dx.doi.org/10.1038/s41467-019-11513-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684615PMC
August 2019

Cloxiquine, a traditional antituberculosis agent, suppresses the growth and metastasis of melanoma cells through activation of PPARγ.

Cell Death Dis 2019 05 28;10(6):404. Epub 2019 May 28.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.

Melanoma is one of the most aggressive skin cancers and 5-year survival rate is only 4.6% for metastatic melanoma patients. Current therapies, especially those involving clinical chemotherapy drugs, have achieved remarkable advances. However, their side effects, such as bone marrow suppression, limit the effectiveness of available pharmacological therapies. Therefore, exploring new antimelanoma drugs with less toxicity is critical for the treatment of melanoma. In the present study, we aimed to identify the antimelanoma drugs with ability to repress the proliferation of melanoma cells by using a high-content screening of FDA-approved drug libraries. We found that cloxiquine (CLQ), a traditional antituberculosic drug, exhibited strong inhibitory effects on the growth and metastasis of melanoma cells both in vivo and in vitro. In contrast, CLQ at the tested doses did not show any apparent toxicity in normal melanocytes and in the liver. At the metabolic level, treatment with CLQ decreased glycolysis, thus potentially inhibiting the "Warburg effect" in B16F10 cells. More importantly, combination of CLQ and 2-deoxyglucose (2-DG), a well-known glycolysis inhibitor, did not show a synergistic effect on the tumor growth and metastasis, indicating that inhibition of glycolysis is potentially involved in mediating CLQ's antimelanoma function. Bioinformatics analyses revealed that peroxisome proliferator-activated receptor-gamma (PPARγ) served as a potential CLQ target. Mechanistically, CLQ stimulated the transcription and nuclear contents of PPARγ. Furthermore, the specific PPARγ inhibitor GW9662 or PPARγ shRNA partially abolished the effects of CLQ. Collectively, our findings demonstrate that CLQ has a great potential in the treatment of melanoma through activation of PPARγ.
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http://dx.doi.org/10.1038/s41419-019-1644-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538643PMC
May 2019

Chronic exposure to green light aggravates high-fat diet-induced obesity and metabolic disorders in male mice.

Ecotoxicol Environ Saf 2019 Aug 15;178:94-104. Epub 2019 Apr 15.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, PR China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, PR China. Electronic address:

Light is involved in many critical physiological or biochemical processes of human beings, such as visual sensing and the production of vitamin D. Recent studies have showed that the lights of different wavelengths have a profound influence in life activities. For example, blue light promotes alertness, whereas green light (GL) induces sleep in mice. On the other hand, metabolic homeostasis is regulated by a variety of factors, including dietary habits and light exposure. Our study aims to study whether certain wavelength of light would affect metabolic status of mice. Mice were divided into normal diet-fed group and high-fat diet (HFD)-fed group, and then exposed to various colors of the light. Physiological parameters, such as body weight, food intake and water drinking were regularly measured. Glucose tolerance test and pyruvate tolerance test were simultaneously performed. After mice were humanely sacrificed, liver histology and serologic analysis were performed for detecting lipid levels. We found that GL group showed obvious glucose intolerance and increased levels of serum and liver lipid contents compared to white light group. Meanwhile, the expression levels of lipid metabolism-related genes were almost down-regulated in liver. Furthermore, melatonin receptor-1b and thyroid hormone receptor-β expression levels were significantly lowered in liver of GL-treated obese mice, suggesting that these hormone pathways may mediate the changes of lipid metabolism. Our data indicate that GL has a detrimental effect on the energy metabolism and aggravates HFD-induced obesity in mice. In addition to malnutrition, the colors of the lights also have a profound influence in the metabolic homeostasis and should be taken into consideration in the therapy of metabolic disorders.
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http://dx.doi.org/10.1016/j.ecoenv.2019.04.013DOI Listing
August 2019

In vivo gum arabic-coated tetrahydrobiopterin protects against myocardial ischemia reperfusion injury by preserving eNOS coupling.

Life Sci 2019 Feb 19;219:294-302. Epub 2019 Jan 19.

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Key Laboratory of Organ Transplantation, Ministry of Education, China; NHC Key Laboratory of Organ Transplantation, China; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, China.

Aims: Exogenous tetrahydrobiopterin (BH), an indispensable cofactor of endothelial nitric oxide synthase (eNOS), supplementation has been proved to be of advantage to improve cardiovascular function. Nevertheless, due to its highly redox-sensitive and easy to be oxidized, there is an urgent need to develop an appropriate BH4 formulation for clinical therapy. Gum Arabic (GA) has been considered as an alternative biopolymer for the stabilization and coating of drugs. The effects of GA on protecting BH from being oxidized were investigated in a rat model of myocardial ischemia-reperfusion (I/R).

Main Methods: Rats were subjected to 60-min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic GA-coated BH supplementation (10 mg/kg, oral). Myocardial infarction, fibrotic area and left ventricle ejection fraction were correlated with cardiac BH content, eNOS protein, NOS enzyme activity, and ROS/NO generation.

Key Findings: Pretreatment of rats with GA-coated 6R-BH, 24 h before myocardial ischemia, resulted in smaller myocardial infarction, improved left ventricular function and inhibited fibrosis, correlated with maintained high levels of cardiac BH content, preserved eNOS activation and dimerization, and decreased ROS generation. However in uncoated group, 6R-BH treatment did not reduce acute and chronic myocardial I/R injury compared with control I/R rats, which was closely related with the marked loss of myocardial BH4 levels during I/R.

Significance: These findings provide evidence that in vivo pre-ischemic oral GA-coated BH administration preserves eNOS function secondary to maintaining cardiac BH content, and confers cardioprotection after I/R.
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http://dx.doi.org/10.1016/j.lfs.2019.01.026DOI Listing
February 2019

Phenotypic and genotypic characterization of antimicrobial resistance profiles in Streptococcus dysgalactiae isolated from bovine clinical mastitis in 5 provinces of China.

J Dairy Sci 2018 Apr 4;101(4):3344-3355. Epub 2018 Feb 4.

College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing 100193, P. R. China. Electronic address:

Bovine mastitis is among the most prevalent and costly diseases of dairy animals and is caused by a variety of bacterial pathogens including Streptococcus dysgalactiae. However, comprehensive studies reporting the prevalence and antimicrobial resistance profiles of S. dysgalactiae isolated from bovine mastitis are scarce. Therefore, this study was to investigate the occurrence of S. dysgalactiae associated with bovine clinical mastitis, to assess their antimicrobial resistance profiles, and to analyze the phenotypic and genotypic profiling of resistant isolates. In total, 1,180 milk samples were collected from dairy cows with clinical mastitis belonging to 74 commercial dairy herds located in 14 provinces of China from January 2014 to May 2016. Overall S. dysgalactiae isolates were recovered from 88 (7.5%) of the mastitic milk samples. The antimicrobial susceptibility of these isolates was tested against 8 antimicrobial agents by using minimum inhibitory concentrations. Results showed that 82 (93.2%) isolates expressed resistance to more than one antimicrobial agent. Antimicrobial resistance was highest against kanamycin (89.8%), sulfonamide (83.0%), and streptomycin (58.0%), which can be attributed to the intrinsic resistance for most of Streptococcus spp. against those antimicrobial substances. Strikingly, 30 (34.1%) and 12 (13.6%) isolates were found resistant to cephalexin and ceftriaxone, respectively. BlaTEM, ermB, and tetM were the most prevalent resistance genes. All isolates carried at least one of all tested resistance genes. Also, 1.1, 12.5, 18.2, 36.4, and 31.8% of isolates were positive for at least one tested resistance gene in 1, 2, 3, 4, or 5 classes of antimicrobials. Survival analysis showed a significant association between ermB and survival of the S. dysgalactiae isolates at increasing erythromycin concentrations. No other statistically significant associations were observed between the phenotypic and genotypic resistance profiles. This study concludes a considerable prevalence of S. dysgalactiae associated with bovine mastitis in dairy herds of China and these isolates exhibited high resistance rates to tested antimicrobials, coupled with high occurrence of resistance genes. Both the prevalence of S. dysgalactiae and their antimicrobial resistance profiles strongly varied among dairy herds, demonstrating the need for antimicrobial susceptibility surveillance at the herd level to ensure optimal therapeutic results.
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http://dx.doi.org/10.3168/jds.2017-14031DOI Listing
April 2018

Characteristics and genetic diversity of multi-drug resistant extended-spectrum beta-lactamase (ESBL)-producing isolated from bovine mastitis.

Oncotarget 2017 Oct 4;8(52):90144-90163. Epub 2017 Oct 4.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China.

A characterization of the drug resistance profiles, identification of PCR-based replicon typing, and multilocus sequence typing (MLST) and analysis of 46 ESBL-producing from cows with mastitis are described. All multidrug-resistant isolates of various phylogenetic groups (A = 31, B1= 3, B2 = 2, D = 10) were ESBL-producers of genotypes CTX-M-15 (29), CTX-M-55 (4), CTX-M-14 (4), CTX-M-3 (1), CTX-M-1 (1), TEM (22) and SHV (8) that were found on conjugative plasmids of diverse incompatibility groups (primarily IncF). Transconjugation experiments indicated successful (100%) trans-conjugation, which was verified phenotypically and genotypically. A total of 28 sequence types (ST) were identified, with 10% of isolates being ST410, and 9 other ST that were assigned arbitrary numbers, reflecting the degree of diversity. Multilocus sequence analysis revealed two lineages, a dominant and a small lineage. Split-decomposition showed intraspecies recombination clearly contributed in genetic recombination generating genotypic diversity among the isolates, and a lack of interspecies recombination. This coherent analysis on genetic structure of multidrug-resistant pathogenic population isolated from mastitic-milk weaponized with resistance elements from a large, rapidly developing country will be a helpful contribution for epidemiology and surveillance of drug resistance patterns, and understanding their global diversity.
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http://dx.doi.org/10.18632/oncotarget.21496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685738PMC
October 2017

Incidence of clinical mastitis and distribution of pathogens on large Chinese dairy farms.

J Dairy Sci 2017 Jun 21;100(6):4797-4806. Epub 2017 Apr 21.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China. Electronic address:

Knowledge of the incidence of clinical mastitis (CM) and the distribution of pathogens involved is essential for development of prevention and control programs as well as treatment protocols. No country-wide study on the incidence of CM and the distribution of pathogens involved has been conducted in China. Core objectives of this study were, therefore, to determine the cumulative incidence of CM and the distribution of pathogens causing CM on large Chinese (>500 cows) dairy farms. In addition, associations between the distribution of CM pathogens and bedding materials and seasonal factors were also investigated. Bacterial culture was done on a total of 3,288 CM quarter milk samples from 161 dairy herds (located in 21 provinces) between March 2014 and September 2016. Additional data, including geographical region of herds, herd size, bedding types, and number of CM cases during the last month, were also recorded. Mean cumulative incidence of CM was 3.3 cases per 100 cows per month (range = 1.7 to 8.1). The most frequently isolated pathogens were Escherichia coli (14.4%), Klebsiella spp. (13.0%), coagulase-negative staphylococci (11.3%), Streptococcus dysgalactiae (10.5%), and Staphylococcus aureus (10.2%). Streptococcus agalactiae was isolated from 2.8% of CM samples, whereas Streptococcus uberis were isolated from 2.1% of samples, and 15.8% of 3,288 samples were culture-negative. Coagulase-negative staphylococci, E. coli, and other Enterobacter spp. were more frequently isolated in the northwest than the northeast or south of China. Streptococcus dysgalactiae, other streptococci, and Strep. agalactiae were more frequently isolated in winter (October-March), whereas E. coli and Klebsiella spp. were mostly isolated in summer (April-September). Streptococcus dysgalactiae was more often isolated from CM cases of herds using sand bedding, whereas Klebsiella spp. and other streptococci were more common in herds using organic bedding. The incidence of CM and distribution of pathogens differed among herds and better mastitis management is needed. Furthermore, geography, bedding materials, and season should be included when designing mastitis control and prevention schemes for Chinese dairies.
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http://dx.doi.org/10.3168/jds.2016-12334DOI Listing
June 2017

Characteristics of Aerococcus viridans isolated from bovine subclinical mastitis and its effect on milk SCC, yield, and composition.

Trop Anim Health Prod 2017 Apr 20;49(4):843-849. Epub 2017 Mar 20.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, 100193, Beijing, People's Republic of China.

Aerococcus viridians (A. viridans), an environmental Gram-positive bacterium, has been documented to be associated with bovine mastitis. However, its exact role in bovine mastitis and the changes it brings about in milk characteristics are not yet known. The objectives of the current study were to describe the antibiotic resistance of A. viridans from bovine mastitis as well as the correlation between existence of this pathogen in udders and the somatic cell counts (SCC), daily milk yield, and composition of individual cow. One-year sampling for subclinical mastitis composite milk was conducted based on monthly DHI data from September 2013 to August 2014, in a commercial herd located in Beijing, China. All samples were cultured and pathogens were identified using microbiology method. A. viridians isolates were further identified by API identification system and 16S ribosomal RNA (rRNA) sequencing method. Kirby-Bauer disk diffusion method was used to test the antibiotic resistance of A. viridians against kinds of antimicrobial substance. SCC, milk yield, and milk composition data were from monthly Dairy Herd Improvement (DHI) results. Results showed that a total of 279 (16.67%) A. viridans isolates were identified from among 1674 bacterial isolates cultured from milk samples with high SCC. The incidence of mastitis caused by A. viridans was the highest (48-53%) during the summer season. Majority of the isolates were susceptible to most of antimicrobial compounds tested, especially to β-lactams, but were found to be resistant (50-90%) to aminoglycosides, sulfonamides, and tetracycline. The average SCC of the A. viridans infected cows was significantly higher (1000.0 × 10 cells/mL) (P < 0.01) as compared to healthy cows (72.4 × 10 cells/mL) and daily milk yield decreased (P > 0.05) by 1.86 kg/day. Reductions were also observed in fat content (P > 0.05), lactose (P < 0.01), and total solids (P > 0.05), whereas protein content increased significantly (P < 0.01) in milk samples of cows infected with A. viridans. The results of this study suggest that A. viridans could be considered as an emerging aetiological agent of bovine subclinical mastitis wherein it exerts an effect on SCC, milk yield, and composition.
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http://dx.doi.org/10.1007/s11250-017-1271-2DOI Listing
April 2017

The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2.

Mol Cells 2017 Feb 21;40(2):109-116. Epub 2017 Feb 21.

Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, P. R. China.

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase ( < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 ( < 0.05). We successfully identified integrins α2, α3, α6, β1, and β4 in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle ( < 0.05). Further analysis indicated that integrin α2, α6, and β1 were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.
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http://dx.doi.org/10.14348/molcells.2017.2207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339501PMC
February 2017

ESBL-Producing from Cows Suffering Mastitis in China Contain Clinical Class 1 Integrons with CTX-M Linked to IS.

Front Microbiol 2016 30;7:1931. Epub 2016 Nov 30.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University Beijing, China.

The prevalence of pathogenic multi-drug resistant (MDR) extended-spectrum β-lactamase (ESBL)-producing is rapidly increasing, becoming a global concern. In a veterinary context, ESBL-producing are mostly reported in poultry and pigs. Here, we report on the prevalence and characterize ESBL-producing isolated from diverse dairy farms in China. Overall, 36 (23.53%) out of 153 isolates from mastitic milk samples ( = 1252) were confirmed as ESBL-producers by double-disc synergy testing and PCR. Nucleotide analysis of PCR amplicons revealed that was the predominant ESBL gene detected in 28 (77.78%) isolates, with being the major (78.57%) allele encoding for ESBLs. Also, 20 (55.56%) and 6 (16.67%) of the ESBL isolates were carrying and genes, respectively, in singlet or in combination. The majority of these isolates belonged to phylo-group A (69.44%) and D (16.67%). Strikingly, all these isolates were found to be MDR showing high resistance to cephalosporins including the fourth generation cefepime and common non β-lactams. Additionally, class 1 integrons () were found in 30 (83.33%) isolates. Analysis of the class 1 integrons variable regions indicated that they were carrying up to five different gene cassettes conferring resistance to various drugs with a predominant combination of genes in tandem, conferring resistance to aminoglycosides and trimethoprim. However, no ESBL encoding genes were found in the cassettes. Interestingly, 22 (66.11%) of the ESBL isolates were also carrying insertion sequence common region 1 (IS) which was found to be associated with most of the CTX-M genes. Altogether, the current study reports on the high prevalence of ESBL-positive , particularly CTX-M-15, carrying clinical class 1 integrons and IS elements are likely indicative of their rapid and wider dissemination, posing threats to veterinary and public health. To the best of our knowledge, this is the first comprehensive study to report on the alarming high occurrence of ESBL-producing from mastitic cows in China.
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http://dx.doi.org/10.3389/fmicb.2016.01931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127808PMC
November 2016

An Investigation of the Innate Immune Response in Bovine Mammary Epithelial Cells Challenged by Prototheca zopfii.

Mycopathologia 2016 Dec 24;181(11-12):823-832. Epub 2016 Aug 24.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China.

Prototheca zopfii is an important bovine mastitis pathogen, which could result in severe mammary infection. However, the innate immune response in bovine mastitis associated with P. zopfii was not clear. Therefore, the aim of this study is to investigate in vitro innate immune responses implicated by P. zopfii. Bovine mammary epithelial cells (bMECs) were infected with 5.0 × 10 cells/ml P. zopfii genotypes I and II independently, and the mRNA expression of TLR-2, TLR-4, TNF-α, IL-1β, IL-8, NOD-1, NOD-2 and β-defensin-5 was determined by real-time polymerase chain reaction (RT-PCR) over a time course of 1, 3, 6, 12 and 24 h. The detection of the NF-κB p65 protein in nucleus and cytoplasm of infected bMECs over the same time course was evaluated. Results showed that P. zopfii genotype II has ability to up-regulate the expression of TLR-2, TLR-4, TNF-α, IL-1β, IL-8, NOD-1, NOD-2 and β-defensin-5 'more strongly than genotype I. Western blot results showed that when bMECs were challenged by P. zopfii genotype II, the expression of NF-κB p65 protein in the nucleus was up-regulated, while in cytoplasm it appeared to be repressed, which indicated that bMECs partly regulate the innate immune responses and inflammation by the NF-κB signaling pathway while being infected by P. zopfii genotype II. It was concluded that adhesion of genotype II was stronger than genotype I, and therefore the genotype II regulatory ability is more robust than that of the genotype I, which causes inflammation of bovine mammary tissue.
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http://dx.doi.org/10.1007/s11046-016-0053-0DOI Listing
December 2016

The role of selenium in insulin-like growth factor I receptor (IGF-IR) expression and regulation of apoptosis in mouse osteoblasts.

Chemosphere 2016 Feb 17;144:2158-64. Epub 2015 Nov 17.

College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address:

Selenium (Se) is an essential component for animals and human beings. The chemoprotective role of Se, via the regulation of the cell cycle, stimulation of apoptosis and activation of some cytokines among others, is well known; however, the comprehensive effects of Se on the expression of IGF-IR and its regulation of apoptosis have not been investigated. Thus the aim of this study was to report on the effects that different concentrations of Se extert on body weight, blood serum IGF-IR levels and histopathology in mice; and on IGF-IR expression, proliferation and apoptosis in mouse osteoblasts. In vivo experiments showed a significant decrease in body weight, serum levels of IGF-IR and prominent toxicant effects on the liver, kidney, heart and spleen following the administration of defined concentrations of Se for 30 d. However, moderate levels (0.1 mg/kg) of Se gradually improved weight and serum IGF-IR. In vitro osteoblast experiments revealed that at concentrations of 5 × 10(-6) and 10(-5) mol/L Se, MTT activity decreased in comparison with control cells. Cell cycle, TEM and caspase-3 activity supported these observations including an increase in the sub-G1 phase and notable apoptosis in osteoblasts, along with a decrease in the expression of mRNA and protein levels of IGF-IR. Moreover, the MTT activity, mRNA and protein levels of IGF-IR in osteoblasts were decreased and caspase-3 activity was increased in siRNA groups as compared with non-siRNA groups. These data suggest that Se significantly affects IGF-IR expression, and that it contributes to the proliferation and regulation of apoptosis in osteoblasts.
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http://dx.doi.org/10.1016/j.chemosphere.2015.11.003DOI Listing
February 2016

Characterization of Prototheca zopfii Genotypes Isolated from Cases of Bovine Mastitis and Cow Barns in China.

Mycopathologia 2016 Apr 8;181(3-4):185-95. Epub 2015 Oct 8.

College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, 100193, Beijing, People's Republic of China.

Protothecal mastitis, caused mostly by Prototheca zopfii (P. zopfii), is increasing in dairy herds and is being reported globally. The present study was aimed at studying the epidemiology of mastitis and at molecular characterization of P. zopfii isolates from dairy herds and their surroundings in three provinces of China using microbiological, biochemical and molecular methods, and antibiotic susceptibility tests. Samples from milk (n = 620) of mastitic cows and their barns sources (n = 410) including feces, feed, bedding materials and drinking water were analyzed. Among other pathogens recovered from mastitic milk, 84 (13.5%) of the isolates were identified as P. zopfii. All of the P. zopfii isolates recovered from milk were recognized as genotype 2, whereas 58 (73.4%) and 21 (26.6%) isolates from environmental sources were found to be P. zopfii genotypes 1 and 2, respectively. The isolates were susceptible to some antibiotics and antifungal agents, including amikacin (78.1%), streptomycin (58.5%), gentamicin (17.8%), amphotericin B (68.6%) and nystatin (64.4%). Additionally, the two genotypes displayed versatile patterns of susceptibility to different antimicrobials agents. Phylogeny of the genotypes on the basis of 18S SSU rDNA and 28S SSU rDNA was also investigated. The isolates of the two genotypes separated into different clades, and no interrelationship was observed among these as shown by phylogenetic analysis. The genotype 1 isolates from cow barn sources were non-pathogenic and may not present any risk of mastitis. We conclude that P. zopfii genotype 2 might play an important role in bovine mastitis in China.
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http://dx.doi.org/10.1007/s11046-015-9951-9DOI Listing
April 2016

In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate.

Antiviral Res 2012 Jan 23;93(1):118-25. Epub 2011 Nov 23.

School of Public Health, Jilin University, Changchun, Jilin 130021, PR China.

A structural determined heteropolytungstate, [K(4)(H(2)O)(8)Cl][K(4)(H(2)O)(4)PTi(2)W(10)O(40)]·NH(2)OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. EC(50) values were determined to be 54μM for HBeAg, 61μM for HBsAg and 2.66μM for supernatant HBV DNA, as compared to 1671, 1570, 169μM, respectively, for the commercially-available hepatitis B drug adefovir dipivoxil (ADV). Intracellular cccDNA, pgRNA and HBcAg were also found to be decreased by compound 1 in a concentration-dependent manner. Cytotoxicity results showed that compound 1 has low toxicity in HepG 2 cells with CC(50) value of 515.20μM. The results indicate that compound 1 can efficiently inhibit HBV replication in HepG 2.2.15 cells line in vitro. Additionally, compound 1 also shows high anti-SARS activity at an EC(50) of 7.08μM and toxicity with a CC(50) of 118.6μM against MDCK cells.
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http://dx.doi.org/10.1016/j.antiviral.2011.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114352PMC
January 2012
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