Probing relaxation dynamics of a cationic lipid based non-viral carrier: a time-resolved fluorescence study

Lipid vesicles composed of cationic dioctadecyldimethylammonium bromide (DODAB) and neutral 1-monooleoyl-rac-glycerol (MO) are promising non-viral carriers of nucleic acids for delivery into cells. Among them, higher cell transfection efficiency was displayed by DODAB-rich vesicles than those enriched with MO. Structural relaxation of these mixed lipid vesicles plays a key role in their cell transfection efficiency because structural organization of the DODAB-rich vesicles are different from that of the MO-rich vesicles. Polarization-gated anisotropy in conjunction with picosecond resolved emission transients of a novel fluorophore 6-acetyl-(2-((4-hydroxycyclohexyl)(methyl)amino)naphthalene) (ACYMAN) has been employed to probe relaxation dynamics in pure DODAB vesicles, and in mixed vesicles of DODAB with varying content of MO. Both orientational relaxation of ACYMAN and relaxation dynamics of its local environment are retarded significantly in mixed lipid vesicles with increasing MO content, from a mole fraction (χ_MO) of 0.2 to that of 0.8 which is consistent with increased rigidity of the MO-rich (χ_MO > 0.5) vesicles relative to the DODAB-rich (χ_MO < 0.5) vesicles. Therefore, higher structural rigidity of the MO-rich vesicles (χ_MO > 0.5) gives rise to their lower cell transfection efficiency than the more flexible DODAB-rich (χ_MO < 0.5) vesicles as observed in previous in vivo studies (Biochim. Biophys. Acta, Biomembr., 2014, 1838, 2555–2567).

Lipid vesicles composed of cationic dioctadecyldimethylammonium bromide (DODAB) and neutral 1-monooleoyl-rac-glycerol (MO) are promising non-viral carriers of nucleic acids for delivery into cells.     

Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans

Pleurotus ostreatus is one of the widely cultivated edible mushrooms. Water-soluble proteoglycan fractions from P. ostreatus mycelia were purified by alcohol-precipitation, ion exchange and followed by gel permeation (Sephadex G-100) chromatography. Three neutral fractions were found, which had polysaccharide to protein ratios 14.2, 26.4 and 18.3, respectively. These fractions were tested for in vitro and in vivo immunomodulatory and anticancer effects on Sarcoma-180-bearing mouse model. In vivo injection of proteoglycans to Sarcoma-180-bearing mice decreased the number of tumor cells and cell cycle analysis showed that most of the cells were found to be arrested in pre-G(0)/G(1) phase of cell cycle. All of the three proteoglycans elevated mouse natural killer (NK) cell cytotoxicity and stimulated macrophages to produce nitric oxide. The Fourier transform infra red (FTIR) spectra suggested the presence of beta-glycosidic bond in all the fractions. Fraction I strongly interacted with glucose/mannose-specific lectin Concanavalin A (ConA), indicating the presence of large number of terminal sugar with glucose/mannose. Thus, the three neutral proteoglycans derived from the mushroom (P. ostreatus) mycelia could be used as immunomodulators and anti cancer agents.     

Bilateral kainic acid lesions in the rat hilus induce non-linear additive mossy fiber neoinnervation

Kainic acid (KA) lesions of the rat hilus model hippocampal sclerosis and temporal lobe epilepsy. Unilateral hilar cell loss denervates the associational afferents normally projecting to the inner molecular layer (IML) granule cell dendrites, followed by ipsilateral mossy fiber (MF) sprouting. Hilar neurons also project through the hippocampal commissure to the contralateral IML. This study compared densities of IML MF sprouting following unilateral versus bilateral low dose KA lesions, using Neo-Timm stain 30 days later. Unilateral KA (0.4 μg) caused only dense ipsilateral MF sprouting. Bilateral lesions with lower doses of KA (0.1 with 0.2 or 0.3 μg) induced dense bilateral MF sprouting. However, the same low doses of KA injected unilaterally did not induce significant sprouting ipsilaterally or contralaterally. These data show that denervations of both associational and commissural afferents to the same IML dendritic zones of granule cells induce non-linear, additive bilateral MF neoinnervations.     

A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus

We recently described a novel autosomal-dominant genodermatosis, termed familial chilblain lupus, and mapped its genetic locus to chromosome 3p21. Familial chilblain lupus manifests in early childhood with ulcerating acral skin lesions and is associated with arthralgias and circulating antinuclear antibodies. In this study, we report the identification of a heterozygous missense mutation (D18N) in TREX1 encoding the 3′-5′repair exonuclease 1 in affected individuals of the family with chilblain lupus. The homodimeric TREX1 is the most abundant intracellular DNase in mammalian cells. We have recently shown that TREX1 plays a role in apoptotic single-stranded DNA damage induced by the killer lymphocyte protease granzyme A. D18N affects a highly conserved amino acid residue critical for catalytic activity. Recombinant mutant TREX1 homodimers are enzymatically inactive, while wild type/mutant heterodimers show residual exonucleolytic activity, suggesting a heterozygous loss of function. Lymphoblastoid cells carrying the D18N mutation are significantly less sensitive to granzyme A-mediated cell death, suggesting a novel role for this caspase-independent form of apoptosis in the pathogenesis of familial chilblain lupus. Our findings also warrant further investigation of TREX1 in common forms of lupus erythematosus.

Rheumatological manifestations of leprosy

Rheumatological manifestations are common in leprosy. A study was conducted among 30 patients to observe the prevalence and spectrum of rheumatological manifestations in leprosy. Seventeen patients were referred from leprosy clinic from 287 consecutive leprosy cases and 13 patients presented de novo at the rheumatology clinic and later diagnosed to have leprosy. In the first group, the most common manifestation was small and large joints polyarthritis resembling rheumatoid arthritis found in 64.7% cases and in the second group tenosynovitis (38.5%) was the commonest. Rheumatoid factor was positive in 60% cases.     

Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.     

Tuning of structural and optical properties with enhanced catalytic activity in chemically synthesized Co-doped MoS2 nanosheets

Molybdenum disulfide (MoS₂) nanosheets, due to having a highly active nature, being low cost and having unique physical and chemical properties, have shown their efficacy in the catalytic reduction of nitroarenes. Doping of transition metal ions in molybdenum disulfide (MoS₂) nanosheets is a well-known strategy to enhance their catalytic efficiency for the reduction of nitroarenes, however, finding the optimum dopant amount is still a subject of ongoing research. Herein, we have synthesized few-layered cobalt (Co) doped MoS₂ nanosheets with different cobalt content (2%, 4%, 6% and 8%) through the solvothermal approach, taking sodium molybdate dihydrate (Na₂MoO₄·2H₂O), thiourea (CH₄N₂S) and cobalt acetate tetrahydrate [Co(CH₃COO)₂·4H₂O] as precursors and their catalytic performance has been affirmed by monitoring the reduction of p-nitrophenol by NaBH₄ in real time using UV-visible absorption spectroscopy. The 6% Co doped MoS₂ nanosheets have exhibited superior catalytic activity with a pseudo-first order rate constant of 3.03 × 10⁻³ s⁻¹ attributed to the abundant defects in the active edge sites having a dominant metallic 1T phase with Co ion activated defective basal planes, sulphur (S) edges, synergistic structural and electronic modulation between MoS₂ and Co ions and enhanced electron transfer assisted through redox cycling in the active sites. An attempt has also been made to study the manipulation of structural and optical properties with cobalt doping in MoS₂ nanosheets to establish a correlation between the catalytic efficiency and dopant content. This study demonstrates that proper tuning of Co doping in MoS₂ nanosheets paves the way in searching for a potential alternative of a noble metal catalyst for the catalytic reduction of nitroarenes.

The optimal cobalt (6% Co) doped MoS₂ catalyst has shown the highest catalytic activity due to the presence of abundant defects in the active edge sites, having dominant metallic 1T phase with Co ion activated defective basal planes.     

Utility of HEART Pathway in Identifying Low-Risk Chest Pain in Emergency Department

BackgroundChest pain is a common presenting symptom in the emergency department (ED). The HEART (history, electroencephalogram [ECG], age, risk factors, and troponin I) score, with addition of troponin at 3 h, helps to determine appropriate risk stratification of the patients.ObjectiveThis study evaluated the utility of the HEART pathway as a decision aid designed for risk stratification of patients with acute-onset chest pain for early and safe disposition.MethodsThis was a prospective observational study done in a tertiary care center. Focused history, 12-lead ECG, and baseline troponin I level on arrival and at hour 3 were recorded. Subjects were classified as low risk (HEART score 0–3) or high risk (HEART score ≥ 4). Patients with a HEART score of 0–3 with negative troponin I at 3 h were discharged and were followed up for major adverse cardiac events (MACEs) within 30 days of ED presentation.ResultsA total of 250 patients were screened for the study, of which 151 were included for the final analysis. One hundred and two patients (68%) were male and 54% of patients were younger than 45 years. HEART scores of 0 (n = 16), 1 (n = 43), 2 (n = 44), and 3 (n = 48) were observed. There was only 1 MACE (0.7%) in 30 days after ED discharge in the study population. The mean length of ED stay in the low-risk group was 4.5 h.ConclusionsLow-risk patients, as per the HEART pathway, can be discharged safely from the ED, which reduces ED stay and health care resource use.     

Correction: Split-anion solvent extraction of light rare earths from concentrated chloride aqueous solutions to nitrate organic ionic liquids

Correction for ‘Split-anion solvent extraction of light rare earths from concentrated chloride aqueous solutions to nitrate organic ionic liquids’ by Mercedes Regadío et al., RSC Adv., 2018, 8, 34754–34763, DOI: 10.1039/c8ra06055j.

The authors regret that an incorrect figure caption was given for Fig. 5. The correct version is presented below.Open in a separate windowFig. 5Viscosity as a function of the temperature and the organic phase composition: (1) after loading 39 g L⁻¹ of REE in 20 v% Cy923 in [C101][NO₃], (2) pure [C101][NO₃], (3) 20 v% Cy923 in [C101][NO₃] and (4) pure Cy923.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Melatonin accelerates maturation inducing hormone (MIH): induced oocyte maturation in carps

The present communication is an attempt to demonstrate the influence of melatonin on the action of maturation inducing hormone (MIH) on the maturation of oocytes in carps. The oocytes from gravid female major carp Labeo rohita were isolated and incubated separately in Medium 199 containing (a) only MIH (1 microg/ml), (b) only melatonin (at concentrations of 50, 100 or 500 pg/ml), and (c) both melatonin and MIH, but at different time intervals. In the latter group, melatonin was added to the incubating medium either (i) 4 h before addition of MIH, (ii) 2 h before addition of MIH, (iii) co-administered with MIH (0 h interval) or (iv) 2 h after addition of MIH. In each case, oocytes were further incubated for 4, 8, 12 or 16 h post- administration of MIH, and the effects of treatment on oocyte maturation were evaluated by considering the rate (%) of germinal vesicle breakdown (GVBD). Incubation of oocytes in a medium containing only melatonin did not result in GVBD of any oocyte. Nearly all the oocytes underwent GVBD when incubated with MIH for 16 h. Administration of melatonin along with MIH (at 0 h interval) or 2 h after addition of MIH did not result in any significant change in the rate of GVBD compared to that in a medium containing only MIH. However, it was quite interesting to observe that incubation of oocytes with melatonin especially 4 h prior to addition of MIH in the medium, led to an accelerated rate of GVBD in the oocytes. Experiments with the oocytes of another major carp Cyprinus carpio following an identical schedule depicted similar results except a difference in the optimum melatonin dose. In L. rohita, 50 pg/ml melatonin had maximum acceleratory effect on MIH-induced GVBD of oocytes, while it was 100 pg/ml in C. carpio. Further study revealed that pre-incubation with melatonin accelerates the action of MIH on the formation of a complex of two proteins (MPF), a regulatory component called cyclin B and the catalytic component protein kinase known as cyclin-dependent kinase, Cdk1. Densitometric analysis of the immunoblot data collected from the melatonin pre-treated MIH incubated oocytes showed that cyclin B level continued to increase even after 4 h of incubation, and reached the peak after 12 h. Moreover, determination of H1 kinase activity as an indicator of MPF activity in oocytes revealed that melatonin pre-incubation considerably increased MIH stimulation of histone H1 phosphorylation as compared to MIH alone. Thus, the present study demonstrates for the first time that prior incubation with melatonin accelerates the action of MIH on carp oocyte maturation.