We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free ...

Endotoxin, also referred to as lipopolysaccharide (LPS), can stimulate localized or systemic inflammation via the activation of pattern recognition receptors. Additionally, endotoxin and inflammation can regulate intestinal epithelial function by altering integrity, nutrient transport and utilization. The gastrointestinal tract is a large reservoir of both Gram positive and negative bacteria, ...

Exposure to the toxic metalloid arsenic is associated with diabetes and cancer, and causes proteotoxicity and endoplasmic reticulum (ER) stress at the cellular level. Adaptive responses to ER stress are implicated in cancer and diabetes, thus understanding mechanisms of arsenic-induced ER stress may offer insights into pathogenesis. Here, we identify ...

The presence of albuminuria or proteinuria constitutes a sign of kidney damage and, together with the estimation of glomerular filtration rate, is based on the evaluation of chronic kidney disease. Proteinuria is a strong marker for progression of chronic kidney disease, and it is also a marker of increased cardiovascular ...

The blood-brain barrier (BBB) is not simply a physical barrier but a regulatory interface between the central nervous system (CNS) and immune system. The BBB both affects and is affected by the immune system and connects at many levels with the CNS, including the following: (1) the BBB transports cytokines ...

In order to perform their functions, macrophages must be activated either by Th1-type cytokines, such as interferon-gamma which is called classical activation or M1, or by Th2-type cytokines, such as IL-4, IL-10, IL-13, etc. referred as alternative activation or M2. In all of these conditions, macrophages require the uptake of ...

Cellular responses to graphene-based, nanometer-sized materials, such as carbon nanotubes and single-walled carbon nanohorns (SWNHs), have previously been studied at low-uptake levels. Here, by exploiting the availability of large quantities of SWNHs, cytotoxicity and the immunological responses induced by the abundant uptake of these structures were studied in RAW 264.7 ...

Intestinal inflammation is characterized by epithelial disruption, leading to loss of barrier function and the recruitment of immune cells, including neutrophils. Although the mechanisms are not yet completely understood, interactions between environmental and immunological factors are thought to be critical in the initiation and progression of intestinal inflammation. In recent ...

Lysosomal storage diseases (LSD) are a group of heterogeneous disorders caused by defects in lysosomal enzymes or transporters resulting in accumulation of undegraded macromolecules or metabolites. Macrophage numbers are expanded in several LSDs leading to histiocytosis of unknown pathophysiology. Here, we found that mice lacking the equilibrative nucleoside transporter 3 ...

Extracellular tonicity and volume regulation control a great number of molecular and cellular functions including: cell proliferation, apoptosis, migration, hormone and neuromediator release, gene expression, ion channel and transporter activity and metabolism. The aim of this review is to describe these effects and to determine if they are direct or ...

Mannose modified chitosan (MAN-CS) treated poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by the double emulsification method and used for FITC-OVA delivery. The effects of incubation period, NPs concentration and mannose on the uptake of NPs by macrophages were studied with a fluorescence microplate reader, flow cytometry and confocal laser ...

Because diabetic neuropathy (DN) appears to result from oxidative stress in neuronal tissues, antioxidant treatment should counteract the condition. Metallothionein (MT) and superoxide dismutase (SOD) are free-radical scavengers, but their ability to cross biological membranes is limited. Applying cell penetrating peptide technologies, we made Tat-MT and Tat-SOD constructs and tested ...

Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit(®) RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit(®) RS nanoparticles prepared by nanoprecipitation ...

OBJECTIVE: We recently reported that lowering of macrophage free intracellular iron increases expression of cholesterol efflux transporters ABCA1 and ABCG1 by reducing generation of reactive oxygen species. In this study, we explored whether reducing macrophage intracellular iron levels via pharmacological suppression of hepcidin can increase macrophage-specific expression of cholesterol efflux ...

The mammalian oviduct plays a crucial role in the preparation of gametes for fertilisation (transport and final maturation) and fertilisation itself. An increasing number of studies offers a comprehensive overview of the functions of the oviduct and its secretions, but this topic has had limited investigation in the horse. Limited ...

In this study, we report an angiopep-2 modified cationic liposome (ANG-CLP) for the efficient co-delivery of a therapeutic gene encoding the human tumour necrosis factor-related apoptosis-inducing ligand (pEGFP-hTRAIL) and paclitaxel (PTX) to glioma. The dual targeting co-delivery system (ANG-CLP/PTX/pEGFP-hTRAIL) improved uptake and gene expression not only in U87 MG cells ...

Magnetic nanoparticles are currently used for precise drug delivery and as an image contrast agent. In the present study, the potentiality of curcumin-loaded magnetic nanoparticles (Cur-MNPs) for the treatment of chronic myeloid leukemia (CML) was investigated. For active therapy, transferrin (Tf) ligand was further conjugated to Cur-MNPs, which demonstrated enhanced ...

To analyse the hypothesis as to whether there is a functional relationship between human cationic amino acid transporters (hCATs, y(+) transporter, the main transporter of l-arginine and l-lysine) and human β-defensin (important components of immune function) production on the ocular surface, arginase and nitrate monoxide synthase (NOS), enzymes that compete ...

Significant progress is being made concerning the development of oligonucleotides as therapeutic agents. Studies with antisense, siRNA, and other forms of oligonucleotides have shown promise in cellular and animal models and in some clinical studies. Nonetheless our understanding of how oligonucleotides function in cells and tissues is really quite limited. ...

Legionella pneumophila, the causative agent of Legionnaires' disease, infects and replicates in macrophages and amoebas. Following internalization, L. pneumophila resides in a vacuole structure called Legionella-containing vacuole (LCV). The LCV escapes from the endocytic maturation process and avoids fusion with the lysosome, a hallmark of Legionella pathogenesis. Interference with the ...

Cyanobacterial microcystins (MCs) represent a toxin group with >100 variants, requiring active uptake into cells via organic anion transporting polypeptides, in order to irreversibly inhibit serine/threonine-specific protein phosphatases. MCs are a human health hazard with repeated occurrences of severe poisonings. In the well known human MC intoxication in Caruaru, Brazil ...

Long-term exposure to pharmacological agents can select for cells that overexpress efflux transporters. We previously showed that mouse J774 macrophages cultivated for a prolonged period of time with toxic concentrations of the fluoroquinolone ciprofloxacin overexpress the efflux transporter Mrp4 and display a reduced accumulation of this antibiotic, but no change ...

RNA interference (RNAi) is an important part of the cell's defenses against viruses and other foreign genes. Moreover, the biotechnological exploitation of RNAi offers therapeutic potential for a range of diseases for which drugs are currently unavailable. Unfortunately, the small interfering RNAs (siRNAs) that are central to RNAi in the ...

Polyethylenimine (PEI) is one of the most effective and widely used cationic macromolecules in experimental gene transfer/therapy protocols. However, the further clinical application of PEI is largely impeded by its cytotoxicity. Here we performed a fundamental investigation on the mechanism of PEI-induced cytotoxicity in both hepatic and nephritic cell lines. ...

This study assessed changes in phagocyte function and activation of the sympatho-adrenal medullary and hypothalamo-pituitary adrenal axes of beluga whales (Delphinapterus leucas) in response to translocation and introduction to a novel social environment. Transported belugas exhibited increases in epinephrine (E), norepinephrine (NE), and cortisol levels in response to the translocation ...

BACKGROUND: Multicellular organisms regulate the uptake of calories, trace elements, and other nutrients by complex feedback mechanisms. In the case of iron, the body senses internal iron stores, iron requirements for hematopoiesis, and inflammatory status, and regulates iron uptake by modulating the uptake of dietary iron from the intestine. Both ...

ABSTRACT: We review the current literature on the molecular mechanisms involved in the pathogenesis of acute kidney injury induced by plasma mediators released by mechanical ventilation. A comprehensive literature search in the PubMed database was performed and articles were identified that showed increased plasma levels of mediators where the increase ...

In some settings increasing high density lipoprotein (HDL) levels has been associated with a reduction in experimental atherosclerosis. This has been most clearly seen in apolipoprotein A-I (apoA-I) transgenic mice or in animals infused with HDL or its apolipoproteins. A major mechanism by which these treatments are thought to delay ...

The blood-brain barrier (BBB) provides a vast interface for cytokines to affect CNS function. The BBB is a target for therapeutic intervention. It is essential, therefore, to understand how cytokines interact with each other at the level of the BBB and how secondary signals modulate CNS functions beyond the BBB. ...

The antitumor agent 11β (CAS # 865070-37-7), consisting of a DNA damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. ...

There is evidence that long chain n-3 PUFA (such as from fish oils) provide atheroprotection through, in part, changes in macrophage function although it has not been fully determined whether these n-3 PUFA target cellular mechanisms that control macrophage foam cell formation. Therefore, we investigated whether the n-3 PUFA, EPA ...

Bioflavonoids are of considerable interest to human health as these serve as antioxidant and anticancer agents. Although epidemiological and experimental studies suggest that luteolin, a natural bioflavonoid, exhibits chemopreventive properties, its effectiveness as an antiproliferative agent against multidrug resistant (MDR) cancers is unclear. We thus assessed the antiproliferative effects of ...

Type I class A macrophage scavenger receptor (SR)-AI plays an important role in foam cell formation and in apoptosis in atherosclerosis, however the mechanism remains unclear. Therefore, we generated a pEGFP-C1-SR-AI plasmid construct for transient transfection of 293T human embryonic kidney cells and observed if SR-AI expression led: (i) to ...

Fluoroquinolones enter eukaryotic cells but the correlation between cellular accumulation and activity remains poorly established. Gemifloxacin is known to accumulate to a larger extent than most other fluoroquinolones in tissues. Using murine J774 macrophages and human THP-1 monocytes, we show that gemifloxacin accumulates more than ciprofloxacin and even moxifloxacin. Whilst ...

The apoptotic phenomena observed in tissues which are subdued to ischemia and then to technical therapeutics of perfusion keep causing serious problems in the patient's clinical recovery. Then, they constitute a challenge to resolve. The objective of this work is to discuss the intracellular mechanisms that lead cells to apoptosis ...

Purpose. Simple sphingolipids control crucial cellular processes in several cell types. We demonstrated that sphingolipids such as ceramide, sphingosine and sphingosine-1-phosphate are key mediators in the regulation of survival, differentiation and proliferation of retina photoreceptors. Ceramide-1-phosphate (C1P) regulates growth and survival in several cell types; however, little is known concerning ...

Quantum dots (QDs) are nanoparticles with strong fluorescent emission and are novel tools used in biomedical applications, but the toxicity and mechanism of cellular uptake are poorly understood. QD655-COOH (negative charge, 18 nm) consist of a cadmium/selenide core and a zinc sulfide shell with a carboxylic acid coating with an ...

Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cells. The present review is focused ...

The objective was to investigate measures of cellular innate immune responses among calm and temperamental Brahman bulls in response to handling and transportation. Sixteen Brahman bulls (344±37d of age; 271.6±45.5kg BW) classified as either calm (n=8) or temperamental (n=8) were loaded onto a trailer, transported for 4h to a novel ...

Administration of the proinflammatory molecule lipopolysaccharide (LPS) alters transport rates for many peptides across the blood-brain barrier (BBB). We and others have previously shown that effects of LPS on BBB transport are highly dependent on the injection paradigm used, and timing of the study. Cytokine expression in both brain and ...

Toll-like receptor-7 (TLR7) and 9, innate immune sensors for microbial RNA or DNA, have been implicated in autoimmunity. Upon activation, TLR7 and 9 are transported from the endoplasmic reticulum (ER) to endolysosomes for nucleic acid sensing by an ER-resident protein, Unc93B1. Little is known, however, about a role for sensor ...

Aims: While numerous studies have reported on nanoparticle uptake by phagocytic cells, the mechanisms of this uptake are poorly understood. A metastudy of research focusing on biological particulate matter has postulated that nanoparticles cannot be phagocytosed and therefore must enter cells via pinocytosis. The purpose of this study was to ...

Background: It has been demonstrated that phosphate uptake through the type III sodium-dependent phosphate co-transporter, Pit-1, induced apoptosis of aortic vascular smooth muscle cells and endothelial cells in vitro. However, the apoptotic effects of high phosphate (HP) level in human peritoneal mesothelial cells (HPMCs) are not known. Methods: To examine ...

Vaccine adjuvants stimulate the innate immune system and determine the outcome of the immune response induced. A better understanding of their action is therefore crucial to the development of new and safer vaccines. Monophosphoryl lipid A (MPL), a 'detoxified' version of lipolysaccharide, is a promising new adjuvant component in human ...

Chelerythrine, formerly identified as a protein kinase C inhibitor, has also been shown to inhibit the anti-apoptotic Bcl-2 family proteins. However, recent studies have now demonstrated that chelerythrine can induce the loss of mitochondrial membrane potential (ΔΨ(m)), a membrane permeability transition (MPT), and the subsequent activation of the mitochondrial apoptotic ...

BACKGROUND: Murine basophils can contribute to the T(H)2 polarization of the immune response by providing rapidly large amounts of IL-4, which suggests that pharmacologic downregulation of this cytokine might provide a strategy to attenuate pathologies associated with excessive production. OBJECTIVE: We examined a number of physiological and pharmacologic ligands of ...

Polyamines are organic polycations expressed by all living organisms, which are known to play an essential role in cell proliferation and differentiation. Recent studies revealed their involvement also in cell contractility and migration and in programmed cell death. These processes are known to contribute to restenosis, a pathophysiological process occurring ...

Dendritic cells (DC) are professional antigen-presenting cells that have the ability to detect infectious materials; antigens to T lymphocytes, and serve as a bridge between innate and adaptive immunities. DC express the ATP-binding cassette transporters P-glycoprotein (P-gp). P-gp is a 170-kDa transmembrane protein encoded by the mdr-1 gene, a member ...

BACKGROUND: Immunomodulation by probiotic microorganisms has become a topic of increasing interest in food microbiology. Polysaccharides are broadly used in the food industry as gelling, thickening, stabilizing, or emulsifying agents. Some probiotics such as lactic acid bacteria also produce exopolysaccharides that stimulate macrophage production of cytokines. The aim of this ...

Burkholderia pseudomallei, a causative agent of melioidosis, is a Gram-negative facultative intracellular bacterium that can survive and multiply in macrophages. Previously, we demonstrated that B. pseudomallei failed to activate gene expression downstream of the MyD88-independent pathway, particularly the expression of beta interferon (IFN-β) and inducible nitric oxide synthase (iNOS), leading ...