Objective: Chronic pancreatitis is the consequence of multiple episodes of recurrent acute pancreatitis (RAP). We hypothesized that apigenin can minimize the sequelae of RAP by limiting acinar cells' proinflammatory signaling pathways.
Methods: AR42J acinar cells were treated in vitro with transforming growth factor β (TGF-β), apigenin, and other inhibitors.
Objectives: Transforming growth factor β (TGF-β) regulates immune and fibrotic responses of chronic pancreatitis. The bone morphogenetic protein 2 (BMP-2) antagonist gremlin is regulated by TGF-β. Parathyroid hormone-related protein (PTHrP) levels are elevated in chronic pancreatitis.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
October 2015
Chronic pancreatitis (CP) is a devastating disease with no treatments. Experimental models have been developed to reproduce the parenchyma and inflammatory responses typical of human CP. For the present study, one objective was to assess and compare the effects of pancreatic duct ligation (PDL) to those of repetitive cerulein (Cer)-induced CP in mice on pancreatic production of bone morphogenetic protein-2 (BMP2), apelin, and parathyroid hormone-related protein (PTHrP).
View Article and Find Full Text PDFCancers (Basel)
June 2015
Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP.
View Article and Find Full Text PDFColorectal carcinoma (CRC) is the third most common cancer in developed countries. A large fraction of cases are linked to chronic intestinal inflammation, with concomitant increased TNF-α release and elevated Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D receptor (VDR) expression, resulting in loss of responsiveness to the protective anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D).
View Article and Find Full Text PDFBackground: Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation, necrosis, and fibrosis. There are currently no drugs limiting pancreatic fibrosis associated with CP, and there is a definite need to fill this void in patient care.
Materials And Methods: Pancreatitis was induced in C57/BL6 mice using supraphysiologic doses of cerulein, and apigenin treatment (once daily, 50 μg per mouse by oral gavage) was initiated 1 wk into the recurrent acute pancreatitis (RAP) protocol.
Am J Physiol Gastrointest Liver Physiol
September 2014
Pancreatitis is a necroinflammatory disease with acute and chronic manifestations. Accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic pancreatitis (CP). Pancreatic parathyroid hormone-related protein (PTHrP) levels are elevated in a mouse model of cerulein-induced AP.
View Article and Find Full Text PDFParathyroid hormone-related protein (PTHrP) enhances prostate cancer (CaP) growth and metastasis in vivo. PTHrP also increases cell survival and migration, and upregulates pro-invasive integrin α6β4 expression. We used the human CaP cell lines C4-2 and PC-3 as model systems to study the mechanisms via which PTHrP regulates α6β4 levels.
View Article and Find Full Text PDFPancreatitis is a common and potentially lethal necro-inflammatory disease with both acute and chronic manifestations. Current evidence suggests that the accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic disease, which is associated with an increased risk of pancreatic cancer. While parathyroid hormone-related protein (PTHrP) exerts multiple effects in normal physiology and disease states, its function in pancreatitis has not been previously addressed.
View Article and Find Full Text PDFParathyroid hormone-related protein (PTHrP) increases the growth and osteolytic potential of prostate cancer cells, making it important to control PTHrP expression. PTHrP expression is suppressed by 1,25-dihydroxyvitamin D(3) (1,25D). The aim of this study was to identify the pathways via which 1,25D exerts these effects.
View Article and Find Full Text PDFParathyroid hormone-related protein (PTHrP) is expressed by human colon cancer tissue and cell lines. Rac1 GTPase enhances colon cancer cell migration and invasion. Here we report a positive correlation between PTHrP expression and Rac1 activity in LoVo (human colon cancer) cells.
View Article and Find Full Text PDFIn this study, we investigated the role of Trypanosoma cruzi invasion and inflammatory processes in reactive oxygen species (ROS) production in a mouse atrial cardiomyocyte line (HL-1) and primary adult rat ventricular cardiomyocytes. Cardiomyocytes were incubated with T. cruzi (Tc) trypomastigotes, Tc lysate (TcTL), or Tc secreted proteins (TcSP) for 0-72 h, and ROS were measured by amplex red assay.
View Article and Find Full Text PDFParathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissues and cancer cell lines. PTHrP enhances tumor cell growth and metastasis in vivo and up-regulates proinvasive integrin alpha6beta4 expression in vitro. Hallmarks of malignant tumor cells include resistance to apoptosis and anchorage-independent cell growth.
View Article and Find Full Text PDFParathyroid hormone-related protein (PTHrP) plays a major role in prostate carcinoma progression and bone metastasis. Once prostate cancers become androgen-independent, treatment options become limited. Vitamin D analogues represent a potentially valuable class of agents in this clinical context.
View Article and Find Full Text PDFTrypanosoma cruzi is the etiologic agent of Chagas' disease, a major health problem in Latin America and an emerging infectious disease in the United States. Previously, we screened a T. cruzi sequence database by a computational-bioinformatic approach and identified antigens that exhibited the characteristics of good vaccine candidates.
View Article and Find Full Text PDFIn this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium.
View Article and Find Full Text PDFWe used 5 diagnostic tests in a cross-sectional investigation of the prevalence of Trypanosoma cruzi in Tejupilco municipality, State of Mexico, Mexico. Our findings showed a substantial prevalence of immunoglobulin G (IgG) and IgM antibodies to T. cruzi in human (n = 293, IgG 2.
View Article and Find Full Text PDFExpert Rev Vaccines
December 2005
The clinically relevant pathognomonic consequences of human infection by Trypanosoma cruzi are dilation and hypertrophy of the left ventricle walls and thinning of the apex. The major complications and debilitating evolutionary outcomes of chronic infection include ventricular fibrillation, thromboembolism and congestive heart failure. American trypanosomiasis (Chagas disease) poses serious public healthcare and budgetary concerns.
View Article and Find Full Text PDFThere is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stress-induced injuries that may contribute to disease progression. Pathogen invasion- and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete.
View Article and Find Full Text PDFTrypanosoma cruzi, a protozoan parasite, is the causative agent for Chagas' disease, which poses serious public health problem in Latin America. The two drugs available for the treatment of this disease are effective only against recent infections and are toxic. Dihydrofolate reductase (DHFR) has a proven track record as a drug target.
View Article and Find Full Text PDFGlycosylphosphatidylinositol (GPI)-anchored proteins are abundantly expressed in the infective and intracellular stages of Trypanosoma cruzi and are recognized as antigenic targets by both the humoral and cellular arms of the immune system. Previously, we demonstrated the efficacy of genes encoding GPI-anchored proteins in eliciting partially protective immunity to T. cruzi infection and disease, suggesting their utility as vaccine candidates.
View Article and Find Full Text PDFIn this study, we evaluated the activities of respiratory chain complexes and oxidative phosphorylation (OXPHOS) capacity of the heart to gain insights into the pathological significance of mitochondrial dysfunction in chagasic cardiomyopathy (CCM). In a murine model of Trypanosoma cruzi infection, biochemical and histochemical analysis of the cardiac mitochondria revealed deficiency of the respiratory chain complexes (CI-CV) in infected mice; the inhibition of CI activity was more pronounced in the acute infection phase, CIII was constitutively repressed throughout the infection and disease phase, and the CV defects appeared in chronic phase only. A substantial decline in cardiac mtDNA content (54-60%) and mitochondria-encoded transcripts (50-65%) with disease development indicated that the alterations in mtDNA contribute to the quantitative deficiencies in respiratory chain activity in chagasic hearts.
View Article and Find Full Text PDFCardiac hypertrophy and remodelling in chagasic disease might be associated with mitochondrial dysfunction. In the present study, we characterized the cardiac metabolic responses to Trypanosoma cruzi infection and progressive disease severity using a custom-designed mitoarray (mitochondrial function-related gene array). Mitoarrays consisting of known, well-characterized mitochondrial function-related cDNAs were hybridized with 32P-labelled cDNA probes generated from the myocardium of mice during immediate early, acute and chronic phases of infection and disease development.
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