Результаты поиска

Implementation of fatty acid carriers to skin irritation and the epidermal barrier.

Acute perturbations are followed by barrier repair and enhanced lipid synthesis, as well as cellular fatty acid trafficking, yet irritation of the skin may be induced by repeat disturbance of barrier function. Recently, new insights in cellular fatty acid transport and metabolism have evolved with respect to skin irritation and barrier disturbances: (1) Employing sodium dodecyl sulfate, skin irritation is accompanied by the induction of an epidermal (E) cytosolic fatty acid binding protein (FABP) associated with enhanced barrier repair. Whether E-FABP contributes to the water barrier function

CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation.

Adenosine A(2A) receptor agonists may be important regulators of inflammation. The aim of this study was to investigate the effects of CGS 21680 (0.1mg/kgi.p.), an agonist of the adenosine (A(2A)) receptor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterised by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of nitric oxide (NO), cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased expression of

Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic mice.

Caspase-8, the proximal enzyme in the death-induction pathway of the TNF/nerve growth factor receptor family, is activated upon juxtaposition of its molecules within the receptor complexes and is then self-processed. Caspase-8 also contributes to the regulation of cell survival and growth, but little is known about the similarities or the differences between the mechanisms of these nonapoptotic functions and of the enzyme's apoptotic activity. In this study, we report that in bacterial artificial chromosome-transgenic mice, in which the aspartate residue upstream of the initial self-processing

Differentiation of naive CTL to effector and memory CTL: correlation of effector function with phenotype and cell division.

Phenotypically and functionally, the early steps of T cell differentiation are not well characterized. In addition, the effector T cell stage shares several phenotypic characteristics with memory T cells, which has made the analysis of T cell memory difficult. In this study, we have investigated in vitro and in vivo the differentiation of naive CTL into effector and memory CTL as a function of cell division using lymphocytic choriomeningitis virus-specific TCR-transgenic spleen cells labeled with the vital dye carboxyfluorescein diacetate, succinimidyl ester. The following major points emerged

Gamma-Delta Phenotypic Evolution in Mycosis Fungoides With CD30-Positive Cutaneous Progression.

CD30-positive large-cell proliferations arising in patients with mycosis fungoides can be diagnostically challenging, particularly when they show variable T-cell receptor expression or gamma/delta (γδ) phenotype. We present two cases of mycosis fungoides (MF) with CD30-positive large cell transformation (LCT)/progression exhibiting γδ T-cell phenotypic evolution. Case 1, a 50-year-old woman, initially presented with hyperpigmented patches and papulonodular lesions showing epidermotropic small-cell MF alongside dermal CD30-positive large cells with a γδ phenotype. Over ten years, she developed

Biomarkers for Diagnosis of Acute Tubulointerstitial Nephritis.

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury among patients who require a kidney biopsy. ATIN is an in … cell expressed and secreted, monocyte chemoattractant protein-1, soluble IL-2 receptor alpha, IL-5, Fas receptor, and others. Imaging studies that reflect kidney inflammation have also been investigated. This review highlights the limitations of currently available tests for ATIN, the biomarkers currently under investigation, and the challenges associated with …

Chlorogenic Acid and its Isomers Attenuate NAFLD by Mitigating Lipid Accumulation in Oleic Acid-Induced HepG2 Cells and High-Fat Diet- Fed Zebrafish.

Chlorogenic acid (Chl), isochlorogenic acid A (Isochl A), and isochlorogenic acid B (Isochl B) are naturally occurring phenolic compounds, which have been shown to exert a regulatory effect on lipid metabolism. However, the mechanism underlying this effect remains unclear. Herein, we investigated the inhibitory effects and underlying mechanisms of these three phenolic compounds on oleic acid (OA)-induced HepG2 cells and high-fat diet (HFD)-fed zebrafish. Lipid accumulation and triacylglycerol levels increased in OA-induced cells, which was attenuated by Chl, Isochl A, and Isochl B. Moreover, t

Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.

Retinal neurodegenerative diseases, including hypertensive retinopathy, involve progressive damage to retinal neurons, leading to visual impairment. In this study, we investigated the pathological mechanisms underlying retinal neurodegeneration in spontaneously hypertensive rats (SHR), using Wistar Kyoto (WKY) rats as normotensive controls. We observed that SHR exhibited significantly higher blood pressure and decreased retinal thickness, indicating retinal neurodegeneration. Molecular tests including quantitative real-time polymerase chain reaction, immunoblot, and immunofluorescent staining

IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results.

BACKGROUND: The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys. METHOD: Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an ex vivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle adminis

Chimeric Antigen Receptor T Cell Therapy and Its Significance in Multiple Myeloma.

Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. After the introduction of chimeric antigen receptor (CAR) T cell therapy, promising results have been evidenced. In this therapy, T cells are derived from the patient and modified in-vitr

Совпадение в полном тексте источника
… The trimerization of the Fas receptor explains the Fas/FasL axis where the Fas ligand causes the activation of caspase 8. Caspase 8 is vital in the formation of caspase 3, a cell death mediator. …

Evaluation of hypocholesterolemic effect of oleuropein in cholesterol-fed rats.

Oleuropein, which is the major compound of olive leaves, has been reported to exert several pharmacological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. The objective of this study was to evaluate the effect of oleuropein on adiponectin level in high cholesterol diet (HCD) induced obesity in rat and the molecular mechanism underlying its activation. Our results showed that orally administered oleuropein (50 mg/kg) by gavage for 8 weeks decreased the body weight, adipose tissue mass and triglyceride and attenuated steatosis in liver. Moreover, the effect

In utero programming of later adiposity: the role of fetal growth restriction.

Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all

TNF-alpha decreases ABCA1 expression and attenuates HDL cholesterol efflux in the human intestinal cell line Caco-2.

HDL cholesterol levels are decreased in Crohn's disease, a tumor necrosis factor-alpha (TNF-alpha)-driven chronic inflammatory condition involving the gastrointestinal tract. ATP-binding cassette transporter A1 (ABCA1), one of several liver X receptor (LXR) target genes, is a cell surface transporter that mediates the rate-controlling step in HDL synthesis. The regulation of ABCA1 and HDL cholesterol efflux by TNF-alpha was investigated in the human intestinal cell line Caco-2. In response to cholesterol micelles or T0901317, an LXR nonsterol agonist, TNF-alpha decreased the basolateral efflux

Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis.

Insulin is a potent adipogenic hormone that triggers the induction of a series of transcription factors and specific proteins governing the differentiation of preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl-terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin signaling and adipogenesis. Uchl3(-/-) mice had less visceral white adipose tissue compared with wild-type mice. In vitro adipogenesis experiments revealed that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3(-/-) mice had impaired ability to differentiate into mature adipoc

Intravenous immunoglobulin preparations and autoimmune disorders: mechanisms of action.

Intravenous immunoglobulins (IVIg) have been used as a substitutive treatment for primary and secondary humoral immune deficiencies for seve … ment of pathogenic autoantibodies clearance, modulation of soluble products, apoptosis blockade via Fas receptor and administration of soluble products which could interfere with the immune response. Both IVIg structure, as well as its obtention from pooled human plasma donors, seem to play an important role in IVIg immunomodulatory properties. Thus, the objec …

Legionella pneumophila induces apoptosis via the mitochondrial death pathway.

Legionella pneumophila has been shown to induce apoptosis within macrophages, monocytic cell lines and alveolar epithelial cells. The mechanisms and significance of L. pneumophila-associated apoptosis are not well understood. It has been speculated that L. pneumophila may induce apoptosis through ligation of death receptors by bacterial surface components or by secreted bacterial factors. Translocation of apoptotic factor(s) through the Dot/Icm secretion machinery followed by direct activation of caspases within the cytosol is discussed as another possible mechanism of apoptosis induction by L

Danshen-Chuanxiong-Honghua ameliorates neurological function and inflammation in traumatic brain injury in rats via modulating Ghrelin/GHSR.

ETHNOPHARMACOLOGICAL RELEVANCE: Guanxin II, proposed by Chen Keji (National master of traditional Chinese medicine), possesses neuroprotective effect. Interestingly, its simplified prescription Danshen-Chuanxiong-Honghua (DCH) can also clinically ameliorate cerebral impairment and improve spatial cognitive deficits, similar to the function of original formula. AIM OF THE STUDY: We aimed to elucidate the rationality of DCH's natural existence, qualitatively identify DCH-derived phytochemicals, thereby to validate cerebral protective effect, and expose the potential mechanism of DCH and its mai

Enhanced T cell apoptosis in common variable immunodeficiency: negative role of the fas/fasligand system and of the Bcl-2 family proteins and possible role of TNF-RS.

CVI is a primary immunodeficiency characterized by a failure of B cell differentiation associated with an array of T cell defects, such as enhanced T cell apoptosis. In this study we investigated the mechanisms underlying CVI enhanced T cell death. We analysed both the expression of Fas using flow cytometry techniques and the expression of FasL mRNA using RT-PCR in CVI T cells. We could not find any significant differences between CVI and normal subjects with regard to Fas expression, although there was a subgroup of CVI patients with very high Fas expression which was accompanied by an up-reg

Ruminant Trans Fatty Acid Intake Modulates Inflammation Pathways in the Adipose Tissue Transcriptome of C57BL/6 Mice.

SCOPE: The study aims to analyze transcriptomic profiles in adipose tissues postconsumption of elaidic acid (EA; trans-18:1n-9) and trans-palmitoleic acid (TPA; trans-16:1n-7), elucidating their different effects on inflammation and glucose metabolism. METHODS AND RESULTS: Twenty C57BL/6 mice are divided into four groups. Each group receives one of the following formulations in drinking water: lecithin nanovesicles, nanovesicles containing either lecithin with EA or TPA (86:14 w/w), or water (control) for 28 days with a regular fat diet (18% calories from fat). Total RNA is extracted, and pai

Enhancing antitumor efficacy of chimeric antigen receptor T cells through constitutive CD40L expression.

Adoptive cell therapy with genetically modified T cells expressing a chimeric antigen receptor (CAR) is a promising therapy for patients with B-cell acute lymphoblastic leukemia. However, CAR-modified T cells (CAR T cells) have mostly failed in patients with solid tumors or low-grade B-cell malignancies including chronic lymphocytic leukemia with bulky lymph node involvement. Herein, we enhance the antitumor efficacy of CAR T cells through the constitutive expression of CD40 ligand (CD40L, CD154). T cells genetically modified to constitutively express CD40L (CD40L-modified T cells) demonstrate