The Protective Effect of L-carnitine on Ionizing Radiation-induced Free Oxygen Radicals

Ionizing radiation is known to generate reactive oxygen species (ROS) that can be removed by antioxidants.  L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain  fatty acids to produce energy. Furthermore it has been shown that L-carnitine is an antioxidant which has  a scavenger effect on ROS and a stabilizing effect on damaged cell membranes. The aim of the study was  to evaluate the potential protective effect of L-carnitine on radiation-induced free radicals in hamsters. Lcarnitine  was given by gavage at a dose of 50 mg/kg for 15 consecutive days before irradiation with a single  dose of 8 Gy. 24 h after radiation exposure, the hamsters were sacrificed and samples were taken from  blood and tissues, and the biochemical and histopatological determinations were carried out. In the irradiated  group, there were significant increases in plasma and liver malondialdehyde (MDA) with marked  reduction in glutathione (GSH) levels in the liver, compared with controls. In red blood cells, superoxide  dismutase (SOD) and catalase activities were also reduced. All these effects were reversed by L-carnitine.  In conclusion, L-carnitine with its antioxidant and free radical scavenging properties could play a modulatory  role against the cellular damage produced by free radicals induced by ionizing radiation.

Nanoengineering of a Negative-Index Binary-Staircase Lens for the Optics Regime

We show that a binary-staircase optical element can be engineered to exhibit an effective negative index of refraction, thereby expanding the range of optical properties theoretically available for future optoelectronic devices. The mechanism for achieving a negative-index lens is based on exploiting the periodicity of the surface corrugation. By designing and nanofabricating a plano-concave binary-staircase lens in the InP/InGaAsP platform, we have experimentally demonstrated at 1.55 microns that such negative-index concave lenses can focus plane waves. The beam propagation in the lens was studied experimentally and was in excellent agreement with the three-dimensional finite-difference time-domain numerical simulations.Comment: 4 pages, 4 figure

Surface plasmon resonance fiber sensor for real-time and label-free monitoring of cellular behavior

This paper reports on the application of an optical fiber biosensor for real-time analysis of cellular behavior. Our findings illustrate that a fiber sensor fabricated from a traditional telecommunication fiber can be integrated into conventional cell culture equipment and used for real-time and label-free monitoring of cellular responses to chemical stimuli. The sensing mechanism used for the measurement of cellular responses is based on the excitation of surface plasmon resonance (SPR) on the surface of the optical fiber. In this proof of concept study, the sensor was utilized to investigate the influence of a number of different stimuli on cells-we tested the effects of trypsin, serum and sodium azide. These stimuli induced detachment of cells from the sensor surface, uptake of serum and inhibition of cellular metabolism, accordingly. The effects of different stimuli were confirmed with alamar blue assay, phase contrast and fluorescence microscopy. The results indicated that the fiber biosensor can be successfully utilized for real-time and label-free monitoring of cellular response in the first 30. min following the introduction of a stimulus. Furthermore, we demonstrated that the optical fiber biosensors can be easily regenerated for repeated use, proving this platform as a versatile and cost-effective sensing tool

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. HCT is a definitive cure for DADA2 with > 95% survival

Healing Potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.

<p>Abstract</p> <p>Background</p> <p>The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, <it>Picrorhiza kurroa </it>in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE₂) and EGF during the process.</p> <p>Methods</p> <p>Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of <it>P. kurroa </it>rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. × 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1^stand 3^rdday of ulceration. The stomach tissues of the mice were used for the biochemical analysis.</p> <p>Results</p> <p>The macroscopic indices revealed maximum ulceration on the 3^rdday after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (<it>P </it>< 0.01), and 76.3% respectively (<it>P </it>< 0.001), compared to the untreated ulcerated mice.</p> <p>Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, <it>P </it>< 0.05) and protein carbonyl (37.7%, <it>P </it>< 0.001), and increased mucin (42.2%, <it>P </it>< 0.01), mucosal PGE₂(21.4%, <it>P </it>< 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, <it>P </it>< 0.05), EGF (149.0%, <it>P </it>< 0.001) and VEGF (56.9%, <it>P </it>< 0.01). Omez reduced the TBARS (29.4%, <it>P </it>< 0.05), and protein carbonyl (38.9%, <it>P </it>< 0.001), and increased mucin (38.3%, <it>P </it>< 0.01), without altering the other parameters significantly.</p> <p>Conclusion</p> <p>PK (20 mg/kg, p. o. × 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.</p

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)

Hematopoietic cell transplantation cures adenosine deaminase 2 deficiency: report on 30 patients

Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-alpha) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.Transplantation and immunomodulatio

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field