Regnase-1 plays an essential role in maintaining skin immune homeostasis via regulation of chemokine expression.

Regnase-1 is an endoribonuclease that regulates the stability of target genes. Here, we investigated whether Regnase-1 plays a regulatory role in the pathophysiology of atopic dermatitis, a chronic inflammatory skin disease. Regnase-1 levels were decreased in skin and serum of atopic dermatitis patients and mice.

Role of Energy Metabolism in the Progression of Neuroblastoma.

Neuroblastoma is a common childhood cancer possessing a significant risk of death. This solid tumor manifests variable clinical behaviors ranging from spontaneous regression to widespread metastatic disease. The lack of promising treatments calls for new research approaches which can enhance the understanding of the molecular background of neuroblastoma.

The cAMP Inducers Modify -Acetylaspartate Metabolism in Wistar Rat Brain.

Neuronal -acetylaspartate production appears in the presence of aspartate -acetyltransferase (NAT8L) and binds acetyl groups from acetyl-CoA with aspartic acid. Further -acetylaspartate pathways are still being elucidated, although they seem to involve neuron-glia crosstalk. Together with -acetylaspartate, NAT8L takes part in oligoglia and astroglia cell maturation, myelin production, and dopamine-dependent brain signaling.

Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the -Acetylaspartate Network in Wistar Rat Brain Cells.

The -acetylaspartate network begins in neurons with -acetylaspartate production catalyzed by aspartate -acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in -acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the -acetylaspartate network.

The Impact of Acetyl-CoA and Aspartate Shortages on the N-Acetylaspartate Level in Different Models of Cholinergic Neurons.

N-acetylaspartate is produced by neuronal aspartate N-acetyltransferase (NAT8L) from acetyl-CoA and aspartate. In cholinergic neurons, acetyl-CoA is also utilized in the mitochondrial tricarboxylic acid cycle and in acetylcholine production pathways. While aspartate has to be shared with the malate-aspartate shuttle, another mitochondrial machinery together with the tricarboxylic acid cycle supports the electron transport chain turnover.

Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas.

The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of and mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples.

A data mining paradigm for identifying key factors in biological processes using gene expression data.

A large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery.

The Level of expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors.

Background/aim: Currently, it has been proposed that combination of 5-fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in colon cancer. Our study aimed to investigate an impact of TWIST1 silencing on the sensitivity of cancer cells to 5FU and selected MAPK inhibitors.

Materials And Methods: The suppression of TWIST1 expression in human colon cancer HT29 and HCT116 cell lines was achieved by transduction with lentiviral vector carrying the TWIST1 silencing sequence (pLL3.

Purinergic signaling in B cells.

Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes.

Overexpression of ID1 reverses the repression of human dental pulp stem cells differentiation induced by TWIST1 silencing.

Unlabelled: Multiple studies showed that the cessation of TWIST1 expression is the prerequisite for osteoblasts' maturation. However, recent reports revealed that the function of TWIST1 is different in the dental pulp stem cells (DPSCs), where a high level of TWIST1 expression promoted DPSCs' differentiation. The aim of the study was to investigate the impact of TWIST1 and ID1 on the differentiation process in the human DPSCs.

Gene expression profile of collagen types, osteopontin in the tympanic membrane of patients with tympanosclerosis.

Background: Tympanosclerosis is a pathological process involving the middle ear. The hallmark of this disease is the formation of calcium deposits. In the submucosal layer, as well as in the right layer of the tympanic membrane, the calcium deposits result in a significant increase in the activity of fibroblasts and deposition of collagen fibers.

Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil.

Adjuvant chemotherapy with 5-fluorouracil remains the basic treatment for patients with advanced colorectal carcinoma. The major obstacle in successful treatment is the ability of CRC cells to acquire chemoresistance. Here we examined the impact of ID1 silencing on the sensitivity of CRC cells to 5-FU.

Altered Expression of Genes Encoding Cornulin and Repetin in Atopic Dermatitis.

Background: It is assumed that beside alterations in the filaggrin gene (FLG), disturbances within genes encoding other cornified envelope proteins are also involved in atopic dermatitis (AD). To identify new potential markers of AD, we studied the polymorphisms of genes encoding repetin (RPTN), cornulin (CRNN), and their expression in the skin of AD patients.

Methods: Polymorphisms in CRNN (rs941934), RPTN (rs284544, rs28441202, rs3001978, and rs12117644), and FLG mutations (R2447X, S3247X) were analyzed by TaqMan genotyping assay and by PCR-RFLP in the blood samples of 159 AD patients and 108 healthy subjects.

Suppression of TWIST1 enhances the sensitivity of colon cancer cells to 5-fluorouracil.

The 5-fluorouracil (5FU)-based adjuvant chemotherapy improves the survival of patients with colorectal cancer, however the main obstacle affecting its effectiveness is a drug resistance. Our study aimed to investigate the impact of TWIST1 silencing on the sensitivity of cancer cells to 5FU. The suppression of TWIST1 expression in human colon cancer HT29 and HCT116 cell lines was achieved by transduction with lentiviral vector carrying the TWIST1 silencing sequence (pLL3.

Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype.

Changes in the expression of cornified envelope (CE) proteins are thought to affect the development and course of atopic dermatitis (AD). The aim of this study was to examine the expression level of CE proteins in order to identify new molecular markers of the AD phenotype. Expression levels of CE proteins were evaluated in the skin of patients with AD (38 biopsies) and healthy subjects (26 biopsies).

Association of a Single Nucleotide Polymorphism in a Late Cornified Envelope-like Proline-rich 1 Gene (LELP1) with Atopic Dermatitis.

There is some evidence that genes involved in the pathogenesis of atopic dermatitis, in addition to the filaggrin (FLG) gene, may be located at chromosome region 1q21. The aim of this study was to examine the association of single nucleotide polymorphisms in the region of the late cornified envelope-like proline-rich 1 (LELP1), hornerin (HRNR) and FLG genes with the course and risk of atopic dermatitis. Single nucleotide polymorphisms and mutations were genotyped by PCR restriction fragment length polymorphism and real-time PCR in a group of 152 patients with atopic dermatitis and 104 healthy volunteers.

AβPP-Transgenic 2576 Mice Mimic Cell Type-Specific Aspects of Acetyl-CoA-Linked Metabolic Deficits in Alzheimer's Disease.

The pyruvate-derived acetyl-CoA is a principal direct precursor substrate for bulk energy synthesis in the brain. Deficits of pyruvate dehydrogenase in the neocortex are common features of Alzheimer's disease and other age-related encephalopathies in humans. Therefore, amyloid-β overload in brains of diverse transgenic Alzheimer's disease model animals was investigated as one of neurotoxic compounds responsible for pyruvate dehydrogenase inhibition yielding deficits of cholinergic neurotransmission and cognitive functions.

Differentiation of high-risk stage I and II colon tumors based on evaluation of CAV1 gene expression.

Background: Several molecular markers are currently being investigated for their prognostic or predictive value in colorectal cancer. One of the genes proposed, as a potential molecular marker in CRC is CAV1.

Methods: The level of CAV1 expression was investigated in low-stage (I and II TNM) colon cancers using Real-Time PCR and immunohistochemistry.

Retinoic acid as a therapeutic option in Alzheimer's disease: a focus on cholinergic restoration.

Retinoic acid is a potent cell differentiating factor, which through its nuclear receptors affects a vast range of promoter sites in brain neuronal and glial cells in every step of embryonic and postnatal life. Its capacities, facilitating maturation of neurotransmitter phenotype in different groups of neurons, pave the way for its application as a potential therapeutic agent in neurodegenerative diseases including Alzheimer's disease. Retinoic acid was found to exert particularly strong enhancing effects on acetylcholine transmitter functions in brain cholinergic neurons, loss of which is tightly linked to the development of cognitive and memory deficits in course of different cholinergic encephalopathies.

Differential effects of lipopolysaccharide on energy metabolism in murine microglial N9 and cholinergic SN56 neuronal cells.

There are significant differences between acetyl-CoA and ATP levels, enzymes of acetyl-CoA metabolism, and toll-like receptor 4 contents in non-activated microglial N9 and non-differentiated cholinergic SN56 neuroblastoma cells. Exposition of N9 cells to lipopolysaccharide caused concentration-dependent several-fold increases of nitrogen oxide synthesis, accompanied by inhibition of pyruvate dehydrogenase complex, aconitase, and α-ketoglutarate dehydrogenase complex activities, and by nearly proportional depletion of acetyl-CoA, but by relatively smaller losses in ATP content and cell viability (about 5%). On the contrary, SN56 cells appeared to be insensitive to direct exposition to high concentration of lipopolysaccharide.

Altered response of fibroblasts from human tympanosclerotic membrane to interacting mast cells: implication for tissue remodeling.

Several lines of evidence suggest that a tympanosclerotic (TMS) lesion often develops secondary to acute and chronic otitis media. Histological findings indicate that fibroblasts and inflammatory cells, including mast cells, play a key role in the tympanosclerotic plaque formation. However, details on the functional characteristics of tympanosclerotic fibroblasts (Fs(TMS)) are scanty.

Intracellular redistribution of acetyl-CoA, the pivotal point in differential susceptibility of cholinergic neurons and glial cells to neurodegenerative signals.

Intramitochondrial decarboxylation of glucose-derived pyruvate by PDHC (pyruvate dehydrogenase complex) is a principal source of acetyl-CoA, for mitochondrial energy production and cytoplasmic synthetic pathways in all types of brain cells. The inhibition of PDHC, ACO (aconitase) and KDHC (ketoglutarate dehydrogenase complex) activities by neurodegenerative signals such as aluminium, zinc, amyloid β-peptide, excess nitric oxide (NO) or thiamine pyrophosphate deficits resulted in much deeper losses of viability, acetyl-CoA and ATP in differentiated cholinergic neuronal cells than in non-differentiated cholinergic, and cultured microglial or astroglial cell lines. In addition, in cholinergic cells, such conditions caused inhibition of ACh (acetylcholine) synthesis and its quantal release.

Expression of TNF-α, OPG, IL-1β and the presence of the measles virus RNA in the stapes of the patients with otosclerosis.

Persistent measles virus infections play a crucial role in the pathomechanism of otosclerosis. The study was undertaken to investigate the role of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and osteoprotegerin (OPG) in otosclerotic bone remodeling and to assess the relation of TNF-α, OPG and IL-1β expression levels in otosclerotic stape footplates to the occurrence of measles virus infection. 61 patients with otosclerosis were treated surgically.

Morphological alterations in the tympanic membrane affected by tympanosclerosis: ultrastructural study.

The ultrastructure of tympanoslerotic tissue, surgically excised from patients, has been studied with particular reference to the morphological changes of the connective tissue components and mineralization. Detailed analysis revealed the combination of degenerative and fibroplastic alterations, especially in the circular fibrous layer of the thickened lamina propria. In the biological material in this study the authors recognized different stages of calcium plaque development with discrete, moderate, and severe degree of mineralization.

Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases.

Glucose-derived pyruvate is a principal source of acetyl-CoA in all brain cells, through pyruvate dehydogenase complex (PDHC) reaction. Cholinergic neurons like neurons of other transmitter systems and glial cells, utilize acetyl-CoA for energy production in mitochondria and diverse synthetic pathways in their extramitochondrial compartments. However, cholinergic neurons require additional amounts of acetyl-CoA for acetylcholine synthesis in their cytoplasmic compartment to maintain their transmitter functions.