Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins

<p>Abstract</p> <p>Background</p> <p>Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-β, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-β signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of <it>TGF-β, Col I</it>, <it>Col III</it>, <it>Col IV</it>, or <it>PAI-1 </it>in liver fibrosis secondary to bile duct injury (BDI).</p> <p>Results</p> <p>Serum TGF-β concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (<it>P </it>< 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-β concentration, Col I and Col III expression, and the amount of fibrosis.</p> <p>Conclusion</p> <p>We found augmented serum concentration of TGF-β and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in <it>Smad7 </it>expression did not inhibit the expression of <it>TGF-β, collagens</it>, and <it>PAI-1</it>. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-β concentration and Smad7 mRNA expression.</p

A drug-resistant leprosy case detected by DNA sequence analysis from a relapsed Mexican leprosy patient.

A skin biopsy sample was obtained from a relapsed lepromatous leprosy patient from the central area of Mexico. Genes associated with resistance to anti-leprosy drugs were analyzed by DNA sequence assay. A single nucleotide substitution was found at codon 53 (ACC-->GCC) in the folP gene, which is known to confer dapsone resistance. No mutations in the rpoB and gyrA, which indicate resistance to rifampicin and fluoroquinoles, were detected. This is the first reported case of dapsone resistant leprosy in Mexico in which the cause of the resistance is shown at genomic level. Evaluation of drug resistance by identifying known mutations in these genes by PCR is simple and reliable. Testing for resistance to anti-leprosy drugs should be performed in relapses or intractable cases for a better outcome

Cytokines: Sensors of the nervous system

The central nervous system (CNS) and the immune system share multiple chemical messengers ranging from small molecules, such as corticotropin-releasing factor (CRF) to large proteins, such as cytokines and growth factors. The immune system is capable of sending signals to the brain through an elaborate system of bi-directional communication. These signals induce responses to the damage caused by viruses, bacteria, parasites and molecules, such as the damage associated molecular pattern molecules (DAMP). The blood-brain barrier prevents the entry of antibodies, complement factors, immune cells and cytokines into the interior of brain parenchyma. Notably, cells of the CNS lack CCR5, B cells, dendritic cells and activated macrophages in a homeostatic state. This organization diminishes immune responses in the brain. It has now been demonstrated that CNS is permanently under the control and surveillance of activated macrophages and dendritic cells, as well as Th cells that are located in the meninges and choroid plexus. These strategic areas can safeguard ventricular and subarachnoid compartments. There are multiple anatomo-physiological connections between the CNS, immune system and autonomous nervous system (ANS) via the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). Cytokines are mediators of intra-and extracellular communications which serve as powerful regulators of neuropeptidergic systems. They maintain neuroendocrine homeostasis, and are involved in responses to stress and depression. Chemokines and prostaglandins (PGs) are essential to generate a powerful response from the immune system. Some of the cytokines involved include TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-12, IL-15, IL-19, IL-18, IL-33 and interferon type I (IFN-β and IFN-α) and type-II (IFN-γ). These molecules act as potent modulators of responses in the neuroendocrine system. In this chapter we review interactions between the immune system and nervous system. © 2012 by Nova Science Publishers, Inc. All rights reserved

Cytokines: Sensors of the nervous system

The central nervous system (CNS) and the immune system share multiple chemical messengers ranging from small molecules, such as corticotropin-releasing factor (CRF) to large proteins, such as cytokines and growth factors. The immune system is capable of sending signals to the brain through an elaborate system of bi-directional communication. These signals induce responses to the damage caused by viruses, bacteria, parasites and molecules, such as the damage associated molecular pattern molecules (DAMP). The blood-brain barrier prevents the entry of antibodies, complement factors, immune cells and cytokines into the interior of brain parenchyma. Notably, cells of the CNS lack CCR5, B cells, dendritic cells and activated macrophages in a homeostatic state. This organization diminishes immune responses in the brain. It has now been demonstrated that CNS is permanently under the control and surveillance of activated macrophages and dendritic cells, as well as Th cells that are located in the meninges and choroid plexus. These strategic areas can safeguard ventricular and subarachnoid compartments. There are multiple anatomo-physiological connections between the CNS, immune system and autonomous nervous system (ANS) via the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). Cytokines are mediators of intra-and extracellular communications which serve as powerful regulators of neuropeptidergic systems. They maintain neuroendocrine homeostasis, and are involved in responses to stress and depression. Chemokines and prostaglandins (PGs) are essential to generate a powerful response from the immune system. Some of the cytokines involved include TNF-?, IL-1, IL-4, IL-6, IL-10, IL-12, IL-15, IL-19, IL-18, IL-33 and interferon type I (IFN-? and IFN-?) and type-II (IFN-?). These molecules act as potent modulators of responses in the neuroendocrine system. In this chapter we review interactions between the immune system and nervous system. 2012 by Nova Science Publishers, Inc. All rights reserved

A drug-resistant leprosy case detected by DNA sequence analysis from a relapsed Mexican leprosy patient.

A skin biopsy sample was obtained from a relapsed lepromatous leprosy patient from the central area of Mexico. Genes associated with resistance to anti-leprosy drugs were analyzed by DNA sequence assay. A single nucleotide substitution was found at codon 53 (ACC-->GCC) in the folP gene, which is known to confer dapsone resistance. No mutations in the rpoB and gyrA, which indicate resistance to rifampicin and fluoroquinoles, were detected. This is the first reported case of dapsone resistant leprosy in Mexico in which the cause of the resistance is shown at genomic level. Evaluation of drug resistance by identifying known mutations in these genes by PCR is simple and reliable. Testing for resistance to anti-leprosy drugs should be performed in relapses or intractable cases for a better outcome

The 3'UTR 1188A/C polymorphism of IL-12p40 is not associated with susceptibility for developing plaque psoriasis in Mestizo population from western Mexico

Obesity is a world health problem that increases the risk for developing type 2 diabetes, cardiovascular disease, fatty liver, and some types of cancer. In postmenopausal women, it represents an important risk factor for the development of breast cancer (BC). Leptin is an adipokine that is secreted by fatty tissue, and high leptin levels are observed both in mouse models of obesity and in obese subjects. High levels of leptin promote the proliferation and progression of various types of cancer, including BC. This review provides a general overview of the biology of leptin, important laboratory studies, and animal and clinical models that have provided evidence for an active role of leptin in the proliferation, progression, and survival of mammary tumors. Finally, this review addresses the most recent studies on the use of leptin receptor antagonists as a novel therapeutic treatment for BC. " Copyright 2013, Mary Ann Liebert, Inc. 2013.",,,,,,"10.1089/jir.2012.0168",,,"http://hdl.handle.net/20.500.12104/45039","http://www.scopus.com/inward/record.url?eid=2-s2.0-84890087045&partnerID=40&md5=4e42411dab3840f78c5b7e7e0e64872

The biology of leptin and its implications in breast cancer: A general view

Obesity is a world health problem that increases the risk for developing type 2 diabetes, cardiovascular disease, fatty liver, and some types of cancer. In postmenopausal women, it represents an important risk factor for the development of breast cancer (BC). Leptin is an adipokine that is secreted by fatty tissue, and high leptin levels are observed both in mouse models of obesity and in obese subjects. High levels of leptin promote the proliferation and progression of various types of cancer, including BC. This review provides a general overview of the biology of leptin, important laboratory studies, and animal and clinical models that have provided evidence for an active role of leptin in the proliferation, progression, and survival of mammary tumors. Finally, this review addresses the most recent studies on the use of leptin receptor antagonists as a novel therapeutic treatment for BC. © Copyright 2013, Mary Ann Liebert, Inc. 2013

Various genotypes of Mycobacterium leprae from Mexico reveal distinct geographic distribution

Objective: To classify Mycobacterium leprae isolates from multiple areas in Mexico based on variable number of tandem repeats of 6 base within the rpoT gene and three single nucleotide polymorphism (SNP), and to analyse their geographic distribution in the context of the origin of leprosy in Mexico. Results: Analysis for rpoT genotyping of 64 samples collected in the west and southwestern areas revealed that 46 isolates were of the 4 copy type and 18 isolates were of the 3 copy type. All samples from the eastern coastal area (n = 24) and from the Yucatan peninsula (n = 12) were of the 3 copy type. Six isolates from the west and southwestern area were SNP-type 1, 13 isolates were SNP-type 2 and 45 isolates were SNP-type 3. Nineteen of 24 isolates from the eastern coastal area were SNP-type 3 and one was SNP-type 4. Seven isolates from the Yucatan peninsula were SNP-type 3 and one was SNP-type 4. Conclusion: The difference of the proportion of each genotype between the western areas and the eastern areas indicated the expansion of leprosy through different paths in Mexico. © Lepra

Various genotypes of Mycobacterium leprae from Mexico reveal distinct geographic distribution

Objective: To classify Mycobacterium leprae isolates from multiple areas in Mexico based on variable number of tandem repeats of 6 base within the rpoT gene and three single nucleotide polymorphism (SNP), and to analyse their geographic distribution in the context of the origin of leprosy in Mexico. Results: Analysis for rpoT genotyping of 64 samples collected in the west and southwestern areas revealed that 46 isolates were of the 4 copy type and 18 isolates were of the 3 copy type. All samples from the eastern coastal area (n = 24) and from the Yucatan peninsula (n = 12) were of the 3 copy type. Six isolates from the west and southwestern area were SNP-type 1, 13 isolates were SNP-type 2 and 45 isolates were SNP-type 3. Nineteen of 24 isolates from the eastern coastal area were SNP-type 3 and one was SNP-type 4. Seven isolates from the Yucatan peninsula were SNP-type 3 and one was SNP-type 4. Conclusion: The difference of the proportion of each genotype between the western areas and the eastern areas indicated the expansion of leprosy through different paths in Mexico. � Lepra