Search Our Scientific Publications & Authors

Cancer Res 2020 12 28;80(24):5491-5501. Epub 2020 Oct 28.

Max Planck Institute for Molecular Genetics, Berlin, Germany.

Chromophobe renal cell carcinoma (chRCC) accounts for approximately 5% of all renal cancers and around 30% of chRCC cases have mutations in . chRCC is poorly supported by microvessels and has markably lower glucose uptake than clear cell RCC and papillary RCC. Currently, the metabolic status and mechanisms by which this tumor adapts to nutrient-poor microenvironments remain to be investigated. Read More

Circ Arrhythm Electrophysiol 2020 08 12;13(8):e008296. Epub 2020 Jul 12.

Department of Medicine (M.D.M., L.H., A.S., A.M., S.P., M.Z., I.B.d.S., M.G.B., J.R., D.D.), Rush University Medical Center.

Background: Epidemiological studies have established obesity as an independent risk factor for atrial fibrillation (AF), but the underlying pathophysiological mechanisms remain unclear. Reduced cardiac sodium channel expression is a known causal mechanism in AF. We hypothesized that obesity decreases Nav1. Read More

Int J Oncol 2020 Jun 20;56(6):1373-1386. Epub 2020 Mar 20.

Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.

Despite enormous scientific advancements in cancer treatment, there is a need for research to combat cancer, particularly bladder cancer. Drugs once proved to be effective in treating bladder cancer have shown reduced efficacy; hence, the cancer recurrence rate is increasing. To overcome this situation, several strategies have been considered, including the development of novel active drugs or modification of existing therapeutic regimens by combining two or more existing drugs. Read More

Hypertension 2020 02 16;75(2):383-392. Epub 2019 Dec 16.

From the Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland (E.J., R.N., P.S., T.J.G., M.S.).

High blood pressure is a risk factor for cardiovascular diseases. Ang II (angiotensin II), a key pro-hypertensive hormone, mediates target organ consequences such as endothelial dysfunction and cardiac hypertrophy. S1P (sphingosine-1-phosphate), produced by Sphk1 (sphingosine kinase 1), plays a pivotal role in the pathogenesis of hypertension and downstream organ damage, as it controls vascular tone and regulates cardiac remodeling. Read More

Food Chem Toxicol 2019 Apr 3;126:303-312. Epub 2019 Mar 3.

Shanghai Institute of Hematology and State Key Laboratory of Medical Genomics, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Rui-jin Road II, Shanghai, 200025, China. Electronic address:

With the introduction of arsenic trioxide and all-trans retinoic acid, the prognosis of acute promyelocytic leukemia has greatly improved. However, all-trans retinoic acid resistance is still unresolved in acute promyelocytic leukemia relapsed patients. In this study, the clinical achievable concentration of 7-hydroxystaurosporine synergized with all-trans retinoic acid to induce terminal differentiation in all-trans retinoic acid resistant acute promyelocytic leukemia cell lines. Read More

Redox Biol 2019 04 21;22:101149. Epub 2019 Feb 21.

Department of Biliary and Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis characterized by its insensitivity to chemotherapy. Emerging evidence indicates that cytoprotective antioxidation is involved in drug resistance of various cancers; however, the underlying molecular mechanisms remain obscure. Here, we demonstrated that atypical protein kinase Cι (aPKCι) mediated reactive oxygen species (ROS) inhibition in a kinase-independent manner, which played a crucial role in tumorigenesis and chemoresistance. Read More

Front Immunol 2018 18;9:2036. Epub 2018 Sep 18.

Pulmonary Division, Faculty of Medicine, Centre de recherche du CHUS and Université de Sherbrooke, Sherbrooke, QC, Canada.

Neutrophils are known to extrude decondensed chromatin, thus forming NETs (neutrophil extracellular traps). These structures immobilize pathogens, thereby preventing their spreading, and are also adorned with antimicrobial molecules. NETs can also influence pathogenesis in chronic inflammation, autoimmunity, and cancer. Read More

Mol Cell Proteomics 2018 12 14;17(12):2434-2447. Epub 2018 Sep 14.

Department of Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612. Electronic address:

Lung cancer is associated with high prevalence and mortality, and despite significant successes with targeted drugs in genomically defined subsets of lung cancer and immunotherapy, the majority of patients currently does not benefit from these therapies. Through a targeted drug screen, we found the recently approved multi-kinase inhibitor midostaurin to have potent activity in several lung cancer cells independent of its intended target, PKC, or a specific genomic marker. To determine the underlying mechanism of action we applied a layered functional proteomics approach and a new data integration method. Read More

PLoS One 2018 5;13(6):e0197362. Epub 2018 Jun 5.

Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, United States of America.

Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR). Read More

Biopharm Drug Dispos 2018 Feb 30;39(2):99-115. Epub 2018 Jan 30.

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada, M5S 3M2.

The vitamin D-deficient model, established in the C57BL/6 mouse after 8 weeks of feeding vitamin D-deficient diets in the absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and a reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. However, there was no change in plasma calcium and phosphate levels. Appraisal of the liver revealed an up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency. Read More

Shock 2018 10;50(4):493-499

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular calcium ([Ca]i) transient that is important for various neutrophil biological functions, e.g. Read More

World J Gastroenterol 2017 Aug;23(29):5313-5323

Hyun Jung Kim, Byung Joo Kim, Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea.

Aim: To investigate the effects of a water extract of Hwangryunhaedok-tang (HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal (ICCs).

Methods: We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an anti-c-kit antibody. Read More

Cancer Res 2017 09 28;77(18):4745-4754. Epub 2017 Jul 28.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.

In prostate cancer, androgen deprivation therapy (ADT) enhances the cytotoxic effects of radiotherapy. This effect is associated with weakening of the DNA damage response (DDR) normally supported by the androgen receptor. As a significant number of patients will fail combined ADT and radiotherapy, we hypothesized that DDR may be driven by androgen receptor splice variants (ARV) induced by ADT. Read More

J Biol Chem 2017 07 24;292(29):12100-12110. Epub 2017 May 24.

Department of Hypertension and Nephrology, Hanover Medical School, 30625 Hanover, Germany. Electronic address:

Kidney disease has been linked to dysregulated signaling via PKC in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. Read More

Mol Biol Cell 2017 Jul 11;28(13):1792-1803. Epub 2017 May 11.

Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Read More

Mol Pharm 2017 06 24;14(6):2147-2157. Epub 2017 May 24.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University , 3584 CG Utrecht, The Netherlands.

The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Read More

Biochim Biophys Acta Gen Subj 2017 Apr 24;1861(4):922-935. Epub 2017 Jan 24.

Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address:

Background: Chelerythrine is widely used as a broad range protein kinase C (PKC) inhibitor, but there is controversy about its inhibitory effect. Moreover, it has been shown to exert PKC-independent effects on non-neuronal cells.

Methods: In this study we investigated possible off-target effects of chelerythrine on cultured cortical rodent neurons and a neuronal cell line. Read More

Psychopharmacology (Berl) 2017 Feb 28;234(4):681-694. Epub 2016 Dec 28.

Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814-4799, USA.

The roles of group I metabotropic glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) and mGluR5, in regulating synaptic plasticity and metaplasticity in the basolateral amygdala (BLA) remain unclear. The present study examined mGluR1- and mGluR5-mediated synaptic plasticity in the BLA and their respective signaling mechanisms. Bath application of the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG) (20 μM), directly suppressed basal fEPSPs (84. Read More

Allergy 2017 Jul 12;72(7):1061-1072. Epub 2017 Jan 12.

Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Biberach, Germany.

Background: Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. Read More

Mol Cell Endocrinol 2017 02 24;442:32-39. Epub 2016 Nov 24.

INRS-Institut Armand-Frappier, 531, Boul. des Prairies, Laval, QC, H7V 1B7, Canada; BioMed Research Centre, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, QC, H3C 3P8, Canada; Center for Interdisciplinary Research on Well-Being, Health, Society and Environment (CINBIOSE), Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, QC, H3C 3P8, Canada. Electronic address:

The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis. Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) receptor/PKC signaling pathway. Norfluoxetine decreased estrogen secretion in the feto-placental co-culture and competitively inhibited catalytic CYP19 activity in BeWo cells. Read More

Neuroscience 2017 01 5;340:384-397. Epub 2016 Nov 5.

Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

The p75 neurotrophin receptor (p75) and its activation of the sphingomyelin signaling cascade are essential for mechanical hypersensitivity resulting from locally injected nerve growth factor (NGF). Here the roles of the same effectors, and of the tropomyosin receptor kinase A (TrkA) receptor, are evaluated for thermal hyperalgesia from NGF. Sensitivity of rat hind paw plantar skin to thermal stimulation after local sub-cutaneous injection of NGF (500ng) was measured by the latency for paw withdrawal (PWL) from a radiant heat source. Read More

Chin J Physiol 2016 Oct;59(5):268-275

Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.

NPC15199 is a synthesized compound that inhibits inflammation in some models. However, whether NPC15199 affects Ca²⁺ homeostasis in human gastric cancer is unclear. This study examined the effect of NPC15199 on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) and viability in SCM1 human gastric cancer cells. Read More

J Neurosci Res 2017 04 21;95(4):1079-1090. Epub 2016 Aug 21.

Psychology Department, Arizona State University, Tempe, Arizona.

Type 5 metabotropic glutamate receptors (mGluR5) activate protein kinase C (PKC) via coupling to G protein signaling. We have previously demonstrated that the epsilon isoform of PKC (PKCɛ) is a critical downstream target of mGluR5 in regulating behavioral and biochemical responses to alcohol. Recent evidence suggests that PKC-mediated phosphorylation of mGluR5 can lead to receptor desensitization and internalization. Read More

Neuroscience 2016 09 30;332:53-60. Epub 2016 Jun 30.

Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address:

Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. Read More

J Recept Signal Transduct Res 2016 Oct 20;36(5):435-44. Epub 2015 Dec 20.

a Laboratory of Hypertension , Research Center in Biological Science, Institute of Exact and Biological Sciences, Federal University of Ouro Preto , Ouro Preto , Brazil .

Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Read More

Pulm Pharmacol Ther 2015 Apr 12;31:55-62. Epub 2015 Feb 12.

Pulmonary, Critical Care, Sleep & Allergy Division of the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA; VA Nebraska-Western Iowa Healthcare System, Research Service and the University of Nebraska Medical Center Pulmonary, Critical Care, Sleep & Allergy Division of the Department of Internal Medicine, Omaha, NE 68198, USA; Department of Environmental, Agricultural, and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address:

Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Read More

Neuropharmacology 2015 Jun 3;93:80-93. Epub 2015 Feb 3.

Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address:

By activating their receptors (OX1R and OX2R) orexin-A/B regulate wake/sleeping states, feeding behaviors, but the function of these peptides in the retina remains unknown. Using patch-clamp recordings and calcium imaging in rat isolated retinal cells, we demonstrated that orexin-A suppressed α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-preferring receptor-mediated currents (AMPA-preferring currents) in ganglion cells (GCs) through OX1R, but potentiated those in amacrine cells (ACs) through OX2R. Consistently, in rat retinal slices orexin-A suppressed light-evoked AMPA-preferring receptor-mediated excitatory postsynaptic currents in GCs, but potentiated those in ACs. Read More

Glia 2015 May 28;63(5):877-93. Epub 2015 Jan 28.

Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.

D-serine is a coagonist of N-methyl-d-aspartate (NMDA) subtype of glutamate receptor and plays a role in regulating activity-dependent synaptic plasticity. In this study, we examined the mechanism by which extracellular ATP triggers the release of d-serine from astrocytes and discovered a novel Ca(2+) -independent release mechanism mediated by P2X7 receptors (P2X7 R). Using [(3) H] d-serine, which was loaded into astrocytes via the neutral amino acid transporter 2 (ASCT2), we observed that ATP and a potent P2X7 R agonist, 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate (BzATP), stimulated [(3) H]D-serine release and that were abolished by P2X7 R selective antagonists and by shRNAs, whereas enhanced by removal of intracellular or extracellular Ca(2+) . Read More

Sheng Li Xue Bao 2014 Dec;66(6):647-57

Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan 430062, China; Department of Pharmacology, Hubei University of Science and Technology, Xianning 437100, China.

A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. Read More

Biochem Cell Biol 2015 Feb 13;93(1):83-93. Epub 2014 Oct 13.

a Laboratory of Hypertesion, Research Center in Biological Science (NUPEB), Institute of Exact and Biological Sciences (ICEB), Federal University of Ouro Preto (UFOP), Campus Morro do Cruzeiro, 35400-000 Ouro Preto, Minas Gerais, Brazil.

Mineralocorticoid receptor (MR) antagonists of aldosterone (spironolactone and eplerenone) display beneficial effects in the treatment of cardiopathies; however, many of these responses are independent of this antagonism. The mechanisms of action of these drugs are not well known; few studies have comparatively evaluated whether eplerenone as well as spironolactone display cardioprotective effects independent of the blockade of aldosterone. To study these mechanisms, which lead to cardioprotective responses, and to evaluate comparatively their effects in vitro, we have evaluated the proliferative effect of spironolactone and eplerenone in primary culture of cardiomyocytes and fibroblasts of neonatal Wistar rats in the presence and absence of aldosterone. Read More