Publications by authors named "Jing-Jing Ji"

17 Publications

  • Page 1 of 1

Periostin promotes arterial calcification through PPARγ-related glucose metabolism reprogramming.

Am J Physiol Heart Circ Physiol 2021 Apr 9. Epub 2021 Apr 9.

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, P.R., China.

Extracellular matrix (ECM) exerts a list of biological functions, contributing to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the functional role of periostin in vascular calcification has yet to be fully described. Ex vivo, recombinant periostin accelerated thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS), which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), recombinant periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition, and suppressed PPARγ expression. Mechanistically, recombinant periostin caused over-activation of glycolysis and mitochondrial dysfunction in VSMCs, as assessed by extracellular acidification rate (ECAR), oxygen consumption rate, and mitochondrial respiratory chain complexes activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment, and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients who underwent computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score of more than zero in patients with coronary artery calcification. There is also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification, partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.
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http://dx.doi.org/10.1152/ajpheart.01009.2020DOI Listing
April 2021

Brain-Derived Neurotrophic Factor, a New Predictor of Coronary Artery Calcification.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029621989813

Department of Cardiology, Xishan Hospital, Wuxi, People's Republic of China.

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.
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http://dx.doi.org/10.1177/1076029621989813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863173PMC
February 2021

Protective role of serpina3c as a novel thrombin inhibitor against atherosclerosis in mice.

Clin Sci (Lond) 2021 Feb;135(3):447-463

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China.

Abnormal vascular smooth muscle cell (VSMC) proliferation is a critical step in the development of atherosclerosis. Serpina3c is a serine protease inhibitor (serpin) that plays a key role in metabolic diseases. The present study aimed to investigate the role of serpina3c in atherosclerosis and regulation of VSMC proliferation and possible mechanisms. Serpina3c is down-regulated during high-fat diet (HFD)-induced atherosclerosis. An Apoe-/-/serpina3c-/--double-knockout mouse model was used to determine the role of serpina3c in atherosclerosis after HFD for 12 weeks. Compared with Apoe-/- mice, the Apoe-/-/serpina3c-/- mice developed more severe atherosclerosis, and the number of VSMCs and macrophages in aortic plaques was significantly increased. The present study revealed serpina3c as a novel thrombin inhibitor that suppressed thrombin activity. In circulating plasma, thrombin activity was high in the Apoe-/-/serpina3c-/- mice, compared with Apoe-/- mice. Immunofluorescence staining showed thrombin and serpina3c colocalization in the liver and aortic cusp. In addition, inhibition of thrombin by dabigatran in serpina3c-/- mice reduced neointima lesion formation due to partial carotid artery ligation. Moreover, an in vitro study confirmed that thrombin activity was also decreased by serpina3c protein, supernatant and cell lysate that overexpressed serpina3c. The results of experiments showed that serpina3c negatively regulated VSMC proliferation in culture. The possible mechanism may involve serpina3c inhibition of ERK1/2 and JNK signaling in thrombin/PAR-1 system-mediated VSMC proliferation. Our results highlight a protective role for serpina3c as a novel thrombin inhibitor in the development of atherosclerosis, with serpina3c conferring protection through the thrombin/PAR-1 system to negatively regulate VSMC proliferation through ERK1/2 and JNK signaling.
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http://dx.doi.org/10.1042/CS20201235DOI Listing
February 2021

LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files.

Brief Bioinform 2020 Oct 30. Epub 2020 Oct 30.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University.

The triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming. Here, we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from variant call format files. It is time and memory saving. In a test dataset with 100 SNPs from 60 000 subjects, it was at least 10.60 times faster and used only 0.03-13.33% of physical memory as compared with other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g. association P-values) and genomic region annotations. It can also compress the SVG files with a large number of SNPs and support subgroup analysis. This fast and convenient tool will facilitate the visualization of LD and haplotype blocks for geneticists.
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http://dx.doi.org/10.1093/bib/bbaa227DOI Listing
October 2020

Serpina3c protects against high-fat diet-induced pancreatic dysfunction through the JNK-related pathway.

Cell Signal 2020 11 20;75:109745. Epub 2020 Aug 20.

Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China. Electronic address:

Background: Serpina3 is a member of the serine protease inhibitor family and is involved in the inflammatory response. In this study, we investigated the effect of Serpina3c on pancreatic function in hypercholesterolemic mice.

Methods: To investigate the role of Serpina3c in hyperlipidaemia, Serpina3c knockout mice were bred with Apoe-knockout mice (on a C57BL/6 background) to generate heterozygous Serpina3c-Apoe double knockout (Serpina3c/Apoe) mice and were then bred to obtain homozygotes. C57BL/6, Serpina3c, Apoe, and ApoeSerpina3c mice were fed normal chow, and Apoe and ApoeSerpina3c mice were fed a high-fat diet (HFD). After feeding for 3 months, the mice were monitored for body weight, blood glucose, glucose tolerance, and insulin tolerance test (ITT). ELISA and immunohistochemistry were used to detect insulin levels and glucagon expression. Immunohistochemical staining for macrophages in the pancreas was also performed. Western blot analysis was performed on pancreatic tissues to detect the protein levels of insulin-associated molecules, the metalloproteinase MMP2, the tissue inhibitor TIMP2 and components of the JNK-related pathway.

Results: Blood glucose levels, glucose tolerance, and ITT were not significantly different among the groups. Serpina3c knockout resulted in blood lipid abnormalities in mice under HFD conditions. Insulin secretion was decreased in ApoeSerpina3c mice compared with Apoe mice under normal chow conditions. In addition, ApoeSerpina3c mice exhibited increased insulin and glucagon secretion and expression after three months of HFD feeding, but insulin secretion was decreased in ApoeSerpina3c mice compared with Apoe mice after the fifth month of HFD feeding. Serpina3c knockout increased MMP2 protein levels, whereas TIMP2 levels in the pancreas were decreased. Furthermore, Serpina3c knockout significantly upregulated the number of macrophages in the pancreas under HFD conditions. The JNK/AKT/FOXO1/PDX-1 axis was found to be involved in Serpina3c-regulated insulin secretion.

Conclusion: These novel findings show that Serpina3c could play a protective role in insulin secretion partly through the JNK-related pathway under HFD conditions.
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http://dx.doi.org/10.1016/j.cellsig.2020.109745DOI Listing
November 2020

Thymosin α1 therapy in critically ill patients with COVID-19: A multicenter retrospective cohort study.

Int Immunopharmacol 2020 Nov 6;88:106873. Epub 2020 Aug 6.

Trauma Research Center, Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General Hospital, Beijing 100048, China. Electronic address:

Background: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients.

Methods: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification.

Results: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa0/FiO (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×10/L, neutrophil >5.3×10/L, lymphocyte < 0.73 × 10/L, PaO/FiO < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7.

Conclusion: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.
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http://dx.doi.org/10.1016/j.intimp.2020.106873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409727PMC
November 2020

Risk factors for long-term prognosis of hepatocellular carcinoma patients after anatomic hepatectomy.

World J Clin Cases 2020 Feb;8(4):713-722

Department of Anesthesiology, Drum Tower Hospital Affiliated with the Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.

Background: The risk factors for patients with major postoperative complications immediately after liver resection have been identified; however, the intermediate and long-term prognoses for these patients have yet to be determined.

Aim: To evaluate the factors responsible for the long-term recurrence-free survival rate in patients with hepatocellular carcinoma (HCC) following anatomic hepatectomy.

Methods: We performed a retrospective analysis of 74 patients with HCC who underwent precise anatomic hepatectomy at our institution from January 2013 to December 2015. The observational endpoints for this study were the tumor recurrence or death of the HCC patients. The overall follow-up duration was three years. The recurrence-free survival curves were plotted by the Kaplan-Meier method and were analyzed by the log-rank test. The value of each variable for predicting prognosis was assessed multivariate Cox proportional hazards regression analysis.

Results: The 1-year and 3-year recurrence-free survival rates of HCC patients were 68.92% and 55.41%, respectively, following anatomic liver resection. The results showed that the 3-year recurrence-free survival rate in HCC patients was closely related to preoperative cirrhosis, jaundice level, tumor stage, maximal tumor diameter, complications of diabetes mellitus, frequency of intraoperative hypotensive episodes, estimated blood loss (EBL), blood transfusion, fluid infusion, and postoperative infection ( < 0.1). Based on multivariate analysis, preoperative cirrhosis, tumor stage, intraoperative hypotension, and EBL were identified to be predictors of 3-year recurrence-free survival in HCC patients undergoing anatomic hepatectomy ( < 0.05).

Conclusion: Tumor stage and preoperative cirrhosis adversely affect the recurrence-free survival rate in HCC patients following anatomic hepatectomy. The long-term recurrence-free survival rate of patients with HCC is closely related to intraoperative hypotension and EBL.
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http://dx.doi.org/10.12998/wjcc.v8.i4.713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052543PMC
February 2020

Diversity of Antimicrobial Peptides in Three Partially Sympatric Frog Species in Northeast Asia and Implications for Evolution.

Genes (Basel) 2020 02 1;11(2). Epub 2020 Feb 1.

Department of Physiology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that play an essential role in innate immunity across taxa from invertebrates to vertebrates. The evolution system of AMP system has not been well explained in the literature. In this study, we cloned and sequenced AMP transcriptomes of three frog species, namely Rana dybowskii, Rana amurensis, and Pelophylax nigromaculatus, which are partially sympatric in northeast Asia, but show different habitat preferences. We found that each species contained 7 to 14 families of AMPs and the diversity was higher in species with a large geographic range and greater habitat variation. All AMPs are phylogenetically related but not associated with the speciation process. Most AMP genes were under negative selection. We propose that the diversification and addition of novel functions and improvement of antimicrobial efficiency are facilitated by the expansion of family members and numbers. We also documented significant negative correlation of net charges and numbers of amino acid residues between the propiece and mature peptide segments. This supports the Net Charge Balance Hypothesis. We propose the Cut Point Sliding Hypothesis as a novel diversification mechanism to explain the correlation in lengths of the two segments.
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http://dx.doi.org/10.3390/genes11020158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073735PMC
February 2020

Promising hen egg-derived proteins/peptides (EDPs) for food engineering, natural products and precision medicines.

Res Vet Sci 2020 Feb 28;128:153-161. Epub 2019 Nov 28.

College of Life Sciences and Food Engineering, Affiliated Hospital, College of Medicine, Hebei University of Engineering, Handan 056002/056021, PR China. Electronic address:

Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.
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http://dx.doi.org/10.1016/j.rvsc.2019.11.011DOI Listing
February 2020

Discovering myeloid cell heterogeneity in the lung by means of next generation sequencing.

Mil Med Res 2019 10 25;6(1):33. Epub 2019 Oct 25.

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

The lung plays a vital role in maintaining homeostasis, as it is responsible for the exchange of oxygen and carbon dioxide. Pulmonary homeostasis is maintained by a network of tissue-resident cells, including epithelial cells, endothelial cells and leukocytes. Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung. Recently developed unbiased next generation sequencing (NGS) has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge. New phenotypes and distinct gene signatures have been identified, and these new findings enhance the diagnosis and treatment of lung diseases. Here, we present a review of the new NGS findings on myeloid cells in lung development, homeostasis, and lung diseases, including acute lung injury (ALI), lung fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer.
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http://dx.doi.org/10.1186/s40779-019-0222-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814050PMC
October 2019

Lactate accelerates calcification in VSMCs through suppression of BNIP3-mediated mitophagy.

Cell Signal 2019 06 6;58:53-64. Epub 2019 Mar 6.

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, PR China. Electronic address:

Arterial media calcification is one of the major complications of diabetes mellitus, which is related to oxidative stress and apoptosis. Mitophagy is a special regulation of mitochondrial homeostasis and takes control of intracellular ROS generation and apoptotic pathways. High circulating levels of lactate usually accompanies diabetes. The potential link between lactate, mitophagy and vascular calcification is investigated in this study. Lactate treatment accelerated VSMC calcification, evaluated by measuring the calcium content, ALP activity, RUNX2, BMP-2 protein levels, and Alizarin red S staining. Lactate exposure caused excessive intracellular ROS generation and VSMC apoptosis. Lactate also impaired mitochondrial function, determined by mPTP opening rate, mitochondrial membrane potential and mitochondrial biogenesis markers. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection for autophagy flux revealed that lactate blocked autophagy flux. LC3-II co-staining with LAMP-1 and autophagosome quantification revealed lactate inhibited autophagy. Furthermore, lactate inhibited mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, LC3-II colocalization with BNIP3 and TEM assays. In addition, BNIP3-mediated mitophagy played a protective role against VSMC calcification in the presence of lactate. This study suggests that lactate accelerates osteoblastic phenotype transition of VSMC and calcium deposition partly through the BNIP3-mediated mitophagy deficiency induced oxidative stress and apoptosis.
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http://dx.doi.org/10.1016/j.cellsig.2019.03.006DOI Listing
June 2019

Calpain-2 protects against heat stress-induced cardiomyocyte apoptosis and heart dysfunction by blocking p38 mitogen-activated protein kinase activation.

J Cell Physiol 2019 07 11;234(7):10761-10770. Epub 2018 Nov 11.

Department of Medicine, Critical Illness Research Center, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.

Cardiovascular dysfunction is a common complication among heatstroke patients, but its underlying mechanism is unclear. This study was designed to investigate the role of calpain-2 and its downstream signal pathway in heat stress-induced cardiomyocyte apoptosis and heart dysfunction. In cultured primary mouse neonatal cardiomyocytes (MNCs), heat stress (43°C for 2 hr) induced a heat-shock response, as indicated by upregulated heat-shock protein 27 (HSP27) expression and cellular apoptosis, as indicated by increased caspase-3 activity, DNA fragmentation and decreased cell viability. Meanwhile, heat stress decreased calpain activity, which was accompanied by downregulated calpain-2 expression and increased phosphorylation of p38, extraceIIuIar signaI-reguIated protein kinase (ERK1/2) and c-Jun N-terminaI kinase (JNK). Calpain-2 overexpression abrogated heat stress-induced apoptosis and phosphorylation of p38 and JNK, but not of ERK1/2. Blocking only p38 prevented heat stress-induced apoptosis in MNCs. In cardiac-specific calpain-2 overexpressing transgenic mice, p38 phosphorylation and cardiomyocyte apoptosis were decreased in the heart tissue of heatstroke mice, as revealed by western blot and terminal deoxynucleotidyl transferase dUTP nick end labelling assays, respectively. M-mode echocardiography also demonstrated that calpain-2 overexpression significantly improved heatstroke-induced decreases in ventricular end-diastolic volume and cardiac output. In conclusion, our study suggests that heat stress reduces calpain-2 expression, which then activates p38, leading to cardiomyocyte apoptosis and heart dysfunction.
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http://dx.doi.org/10.1002/jcp.27750DOI Listing
July 2019

Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.

Bioorg Med Chem Lett 2012 Dec 22;22(24):7351-6. Epub 2012 Oct 22.

Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.

We have synthesized and evaluated a series of novel HCV NS3 protease inhibitors with various P4 capping groups, which include urea, carbamate, methoxy-carboxamide, cyclic carbamate and amide, pyruvic amide, oxamate, oxalamide and cyanoguanidine. Most of these compounds are remarkably potent, exhibiting single-digit to sub-nanomolar activity in the enzyme assay and cell-based replicon assay. Selected compounds were also evaluated in the protease-inhibitor-resistant mutant transient replicon assay, and they were found to show quite different potency profiles against a panel of HCV protease-inhibitor-resistant mutants.
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http://dx.doi.org/10.1016/j.bmcl.2012.10.075DOI Listing
December 2012

Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants.

J Med Chem 2012 Apr 3;55(7):3021-6. Epub 2012 Apr 3.

GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA.

The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.
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http://dx.doi.org/10.1021/jm201278qDOI Listing
April 2012

Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties.

Bioorg Med Chem Lett 2011 Apr 23;21(7):2048-54. Epub 2011 Feb 23.

Anacor Pharmaceuticals, Inc, 1020 E Meadow Circle, Palo Alto, CA 94303, USA.

We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series.
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http://dx.doi.org/10.1016/j.bmcl.2011.02.006DOI Listing
April 2011

Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease.

Bioorg Med Chem Lett 2010 Dec 30;20(24):7493-7. Epub 2010 Oct 30.

Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.

HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1' region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described.
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http://dx.doi.org/10.1016/j.bmcl.2010.10.007DOI Listing
December 2010

Inhibition of lung metastasis in mice by intravascular injection of dendritic cells and natural killer cells.

Biotechnol Lett 2009 Nov 10;31(11):1709-15. Epub 2009 Jul 10.

Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 150086, 246 Xuefu Road, Nangang District, Harbin, Heilongjiang, China.

To investigate the efficacy of dendritic cells and natural killer cells in the inhibition of lung metastasis, we injected dendritic cells and natural killer cells intravascularly into mice bearing B16F10 tumour melanoma cells. This efficiently inhibited tumor growth and prolonged survival. In addition, surviving mice developed a long-lasting memory response against the original tumor when re-challenged with live tumor cells. Intravenous administration of dendritic cells and natural killer cells may be a potential way to treat lung metastasis in patients.
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http://dx.doi.org/10.1007/s10529-009-0072-8DOI Listing
November 2009