Retraction Note to: Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine‑induced hepatic cancer via knock‑down oxidative stress and inflammation

Inflammopharmacology -     

Transient apical ballooning: sheep in wolves' garb

Takotsubo cardiomyopathy is a unique acute cardiac syndrome characterized by typical ischemic chest symptoms, an elevated ST segment on the electrocardiogram, and elevated cardiac disease markers. It is often misdiagnosed as acute myocardial infarction. Coronary angiography usually shows no evidence of obstructive atherosclerotic coronary artery disease. Left ventriculography and echocardiography reveal a peculiar regional systolic dysfunction with akinesis of the midventricle and apex and compensatory hyperkinesis of the basal ventricular segments. This syndrome has been shown to have a distinct temporal relationship with intense emotional stressors, and is characterized by an excellent clinical recovery when appropriate conservative measures are taken during the acute phase of the illness. In this review, we highlight the proposed pathophysiology and clinical manifestations of this recognized reversible form of myocardial failure.     

From the Cover: Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue

Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.The regional distribution and morphology of adipose tissue (AT) are strong predictors of metabolic disease (1–3). Excess lipid deposition in visceral AT (VAT; adipose associated with visceral organs) is associated with increased susceptibility to insulin resistance and type 2 diabetes (4), whereas expansion of subcutaneous AT (SAT; adipose between muscle and skin) is associated with reduced risk for metabolic disease and is even protective against hyperglycemia and dyslipidemia (4–7). In turn, hypertrophic AT morphology (few large adipocytes) is associated with insulin resistance and AT dysfunction, whereas hyperplastic AT morphology (many small adipocytes) is associated with improved metabolic parameters (4, 7–9). Therefore, the identification of factors that regulate regional distribution and AT morphology could lead to new therapies to treat metabolic disease.Genome-wide association studies have implicated the PLEXIN D1 (PLXND1) locus in waist:hip ratio (a measurement of regional AT distribution) and type 2 diabetes (10). However, a role for Plxnd1 in AT morphology, distribution, and metabolism is unknown. Plxnd1 is a transmembrane receptor that controls the migration, proliferation, and survival of diverse cell types (11). Mutation of Plxnd1 in mouse and zebrafish leads to hypervascularization in many tissues (12, 13), and vascular endothelial cell Plxnd1 modulates extracellular matrix (ECM) synthesis and composition by regulating the collagen receptor, β1-integrin (14). In turn, ECM provides a supportive microenvironment for AT growth and function (15). For example, type V collagens regulate collagen fiber assembly, geometry, and strength (16, 17), are up-regulated during adipogenesis, and can stimulate adipocyte differentiation in vitro (18–20). However, the role of type V collagens during in vivo AT growth is unknown.In this study, we use genetic analysis and in vivo imaging of lipid deposition dynamics in zebrafish to assess the role of Plxnd1 in AT morphology and body fat distribution. Previous studies have shown that zebrafish adipocytes and AT are morphologically, molecularly, and functionally homologous to mammalian white AT (21–26), and like mammals, zebrafish adipocytes accumulate a large cytoplasmic lipid droplet (LD) that facilitates the in vivo identification of adipocytes by fluorescent lipophilic dyes (21, 22, 24–26). Here we determine in zebrafish that Plxnd1 functions through Col5a1 to exert a VAT-specific effect on adipose growth and morphology, resulting in altered body fat distribution and improved insulin sensitivity. In accord, molecular and physiological assessments in humans support a conserved role for PLXND1 in regulation of VAT morphology and insulin sensitivity.     

New approaches under development: cardiovascular embryology applied to heart disease

Despite many innovative advances in cardiology over the past 50 years, heart disease remains a major killer. The steady progress that continues to be made in diagnostics and therapeutics is offset by the cardiovascular consequences of the growing epidemics of obesity and diabetes. Truly innovative approaches on the horizon have been greatly influenced by new insights in cardiovascular development. In particular, research in stem cell biology, the cardiomyocyte lineage, and the interactions of the myocardium and epicardium have opened the door to new approaches for healing the injured heart.     

An efficient,mild and metal free l-proline catalyzed construction of fused pyrimidines under microwave conditions in water

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described. Fused pyrimidines have been synthesized under mild reaction conditions using l-proline. The protocol has been performed rapidly and efficiently in water under metal free conditions. Heterocyclic derivatives have been synthesized using the present methodology and avoid the use of hazardous solvents over conventional organic solvents. A proposed mechanism could be established for three component reactions. The present study reveals the first case in which l-proline has been explored as a homogeneous catalyst in the synthesis of fused pyrimidines in water under microwave irradiation. This synthesis involves simple workup and acceptable efficiency. The most notable feature of this protocol is the ability of the catalyst to influence asymmetric induction in the reaction.

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described.     

Chemoprotective potential of Coccinia indica against cyclophosphamide-induced toxicity

Objective:

Although cyclophosphamide (CP), an alkylating agent, is used in the treatment of cancer owing to its broad-spectrum efficacy, its metabolites exhibit severe undesired toxicities in normal cells. The present study was aimed to investigate the chemoprotective potential of Coccinia indica against CP-induced oxidative stress, genotoxicity, and hepatotoxicity.

Materials and Methods:

Rodents were orally pre-treated with Coccinia indica extract (200, 400, and 600 mg/kg) for five consecutive days. On 5th day, these animals were injected with CP (50 mg/kg i.p) and sacrificed after 24 hrs. for the evaluation of oxidative stress, hepatotoxicity, micronucleus formation, and chromosomal aberrations.

Results:

We found that the CP significantly increased malondialdehyde (MDA) and decreased catalase and glutathione (GSH) levels in brain, and it was significantly reversed by Coccinia indica extract (400 and 600 mg/kg). Further, pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly and dose-dependently reduced micronuclei formation and incidence of aberrant cells. We also found that the CP-induced increase in the serum biomarker enzymes like alkaline phosphatase (ALP), alkaline aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly reduced by Coccinia indica extract.

Conclusion:

Thus, the present results indicate the protective effect of Coccinia indica extract against CP-induced oxidative stress, genotoxicity, as well as hepatotoxicity.KEY WORDS: Coccinia indica, cyclophosphamide, genotoxicity, oxidative stress     

Morphology and innervation of the teleost physostome swim bladders and their functional evolution in non-teleostean lineages

Swim bladders and lungs are homologous structures. Phylogenetically ancient actinopterygian fish such as Cladistians (Polypteriformes), Ginglymods (Lepisosteids) and lungfish have primitive lungs that have evolved in the Paleozoic freshwater earliest gnathostomes as an adaptation to hypoxic stress. Here we investigated the structure and the role of autonomic nerves in the physostome swim bladder of the cyprinid goldfish (Carassius auratus) and the respiratory bladder of lepisosteids: the longnose gar and the spotted gar (Lepisosteus osseus and L. oculatus) to demonstrate that these organs have different innervation patterns that are responsible for controlling different functional aspects. The goldfish swim bladder is a richly innervated organ mainly controlled by cholinergic and adrenergic innervation also involving the presence of non-adrenergic non-cholinergic (NANC) neurotransmitters (nNOS, VIP, 5-HT and SP), suggesting a simple model for the regulation of the swim bladder system. The pattern of the autonomic innervation of the trabecular muscle of the Lepisosteus respiratory bladder is basically similar to that of the tetrapod lung with overlapping of both muscle architecture and control nerve patterns. These autonomic control elements do not exist in the bladders of the two species studied since they have very different physiological roles. The ontogenetic origin of the pulmonoid swim bladder (PSB) of garfishes may help understand how the expression of these autonomic control substances in the trabecular muscle is regulated including their interaction with the corpuscular cells in the respiratory epithelium of this bimodal air-breathing fish.     

Multiscale observations of CO2, 13CO2, and pollutants at Four Corners for emission verification and attribution

There is a pressing need to verify air pollutant and greenhouse gas emissions from anthropogenic fossil energy sources to enforce current and future regulations. We demonstrate the feasibility of using simultaneous remote sensing observations of column abundances of CO₂, CO, and NO₂ to inform and verify emission inventories. We report, to our knowledge, the first ever simultaneous column enhancements in CO₂ (3–10 ppm) and NO₂ (1–3 Dobson Units), and evidence of δ¹³CO₂ depletion in an urban region with two large coal-fired power plants with distinct scrubbing technologies that have resulted in ∆NO_x/∆CO₂ emission ratios that differ by a factor of two. Ground-based total atmospheric column trace gas abundances change synchronously and correlate well with simultaneous in situ point measurements during plume interceptions. Emission ratios of ∆NO_x/∆CO₂ and ∆SO₂/∆CO₂ derived from in situ atmospheric observations agree with those reported by in-stack monitors. Forward simulations using in-stack emissions agree with remote column CO₂ and NO₂ plume observations after fine scale adjustments. Both observed and simulated column ∆NO₂/∆CO₂ ratios indicate that a large fraction (70–75%) of the region is polluted. We demonstrate that the column emission ratios of ∆NO₂/∆CO₂ can resolve changes from day-to-day variation in sources with distinct emission factors (clean and dirty power plants, urban, and fires). We apportion these sources by using NO₂, SO₂, and CO as signatures. Our high-frequency remote sensing observations of CO₂ and coemitted pollutants offer promise for the verification of power plant emission factors and abatement technologies from ground and space.Trace gas [nitrogen oxides (NO_x), sulfur dioxide (SO₂), and carbon monoxide (CO)] and carbon dioxide (CO₂) emissions from anthropogenic fossil energy production are major contributors to air pollution and global warming. Under the Clean Air Act, in the United States these emissions are considered a threat to public health and welfare and are regulated by the Environmental Protection Agency (EPA). Although reporting requirements for air pollutants are well established, they are still under development for CO₂. Reported inventories of CO₂ and pollutant gases are calculated for specific activities using emission factors that depend on fuel composition, combustion efficiency, and scrubbing methods. These bottom–up inventories are subject to significant uncertainties and manipulations (1). Alternatively, atmospheric observations offer an independent top–down method to verify emissions of pollutant trace gases that have low atmospheric background levels and exhibit large and distinct increases near various combustion sources. For example, satellite observations of NO₂ have been used to evaluate regional and local emissions (2), but they are only useful for trend analysis, because their large observational footprint can underestimate NO₂. In contrast, background levels of CO₂ are high with significant variability, making source attribution and verification by direct CO₂ measurements elusive (3), limiting our ability to develop an effective global climate treaty or carbon-trading scheme (4). We postulate that measurements of coemitted trace gases and isotopic composition can be used to isolate anthropogenic CO₂ emissions and identify contributions from specific sectors with distinct composition (trace gas-to-CO₂ emission ratios, ER_X = X/CO₂, or isotopic ratio ¹³CO₂/¹²CO₂). We hypothesize that remote column trace gas measurements over large scales, which are less sensitive to small-scale variability from meteorology than in situ point surface measurements, can provide a more precise method for identifying trends in emissions and emission factors (5). We evaluate this method by using extensive ground-based in situ and remote observations, and forward modeling using reported in-stack emissions at a site with large power plant emissions of CO₂ and pollutants.