Hesperetin blocks poxvirus replication with a low tendency to select for drug-resistant viral variants.

In this study, we demonstrated the antiviral efficacy of hesperetin against multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus (VACV), and lumpy skin disease virus (LSDV). The time-of-addition and virus step-specific assays indicated that hesperetin reduces the levels of viral DNA, mRNA, and proteins in the target cells. Further, by immunoprecipitation (IP) of the viral RNA from BPXV-infected Vero cells and a cell-free RNA-IP assay, we demonstrated that hesperetin-induced reduction in BPXV protein synthesis is also consistent with diminished interaction between eukaryotic translation initiation factor eIF4E and the 5' cap of viral mRNA. Molecular docking and MD simulation studies were also consistent with the binding of hesperetin to the cap-binding pocket of eIF4E, adopting a conformation similar to m7GTP binding. Furthermore, in a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane and associated mortality in the chicken embryos. Most importantly, long-term culture of BPXV in the presence of hesperetin did not induce the generation of drug-resistant viral mutants. In conclusion, we, for the first time, demonstrated the antiviral activity of hesperetin against multiple poxviruses, besides providing some insights into its potential mechanisms of action.

Oxidative phosphorylation inhibitors inhibit proliferation of endometriosis cells.

In brief: Developing novel therapies to cure and manage endometriosis is a major unmet need that will benefit over 180 million women worldwide. Results from the current study suggest that inhibitors of oxidative phosphorylation may serve as novel agents for the treatment of endometriosis. Abstract: Current therapeutic strategies for endometriosis focus on symptom management and are not curative. Here, we provide evidence supporting the inhibition of oxidative phosphorylation (OXPHOS) as a novel treatment strategy for endometriosis. Additionally, we report an organotypic organ-on-a-chip luminal model for endometriosis. The OXPHOS inhibitors, curcumin, plumbagin, and the FDA-approved anti-malarial agent, atovaquone, were tested against the endometriosis cell line, 12Z, in conventional as well as the new organotypic model. The results suggest that all three compounds inhibit proliferation and cause cell death of the endometriotic cells by inhibiting OXPHOS and causing an increase in intracellular oxygen radicals. The oxidative stress mediated by curcumin, plumbagin, and atovaquone causes DNA double-strand breaks as indicated by the elevation of phospho-γH2Ax. Mitochondrial energetics shows a significant decrease in oxygen consumption in 12Z cells. These experiments also highlight differences in the mechanism of action as curcumin and plumbagin inhibit complex I whereas atovaquone blocks complexes I, II, and III. Real-time assessment of cells in the lumen model showed inhibition of migration in response to the test compounds. Additionally, using two-photon lifetime imaging, we demonstrate that the 12Z cells in the lumen show decreased redox ratio (NAD(P)H/FAD) and lower fluorescence lifetime of NAD(P)H in the treated cells confirming major metabolic changes in response to inhibition of mitochondrial electron transport. The robust chemotoxic responses observed with atovaquone suggest that this anti-malarial agent may be repurposed for the effective treatment of endometriosis.

Study on Volumetric, Compressibility and Viscometric Behavior of Cationic Surfactants (CTAB and DTAB) in Aqueous Glycyl Dipeptide: A Thermo-Acoustic Approach.

This study aims to understand how glycyl dipeptide affected the compressibility, volumetric behavior and viscometric behavior of the cationic surfactants CTAB (Cetyltrimethylammonium bromide) and DTAB (dodecyltrimethylammonium bromide). Information on solute-solute, solute-solvent, and solvent-solvent interactions has been inferred using the quantification of density (ρ), speed of sound (u) and viscosity in aqueous media containing glycyl dipeptide in the temperature range 293.15-313.15 K at an interval of 5 K. The data from the aforementioned research have been used to enumerate numerous volumetric and compressibility metrics that aid in the collection of information about the interactional behavior of the system under consideration. The study suggests that CTAB interacts strongly compared to DTAB with dipeptide, and it also significantly dehydrates glycyl dipeptide. The difference in water-water interactions caused by the loss of hydrophobic hydration of the surfactant molecules upon the addition of cationic surfactants may be the cause of the variation in determined parameters with surfactant concentration. Consideration of the structural rearrangement of molecules that may occur in the system has been used to explain the results of viscosity and computed factors related to viscosity. The patterns of competitive intermolecular interactions in the ternary (dipeptide + water + surfactant) system have been used to analyze the trends of all the parameters. The study may be helpful to understand the stability and structural changes in protein-surfactant systems mediated through various interactions that may be present in the system.

Volumetric, Compressibility and Viscometric Approach to Study the Interactional Behaviour of Sodium Cholate and Sodium Deoxycholate in Aqueous Glycyl Glycine.

Viscosity, speed of sound (u), and density (ρ) have been measured in aqueous glycyl glycine solution over a temperature range from 293.15 to 313.15 K with a 5 K interlude to evaluate the volumetric and compressibility properties of bio-surfactants, namely sodium cholate (NaC; 1-20 mmol∙kg-1) and sodium deoxycholate (NaDC; 1-10 mmol∙kg-1). Density and viscosity findings provide information on both solute-solute and solute-solvent types of interactions. Many other metrics, such as apparent molar adiabatic compression (κS,φ), isentropic compressibility (κS), and apparent molar volume (Vφ), have been calculated from speed of sound and density measurements, utilising experimental data. The results show that the zwitterionic end group in the glycyl glycine strongly interacts with NaDC and NaC, promoting its micellization. Since the addition of glycyl glycine causes the bio-surfactant molecules to lose their hydrophobic hydration, the observed concentration-dependent changes in apparent molar volume and apparent molar adiabatic compression are likely attributable to changes in water-water interactions. Viscous relaxation time (τ) increases significantly with a rise in bio-surfactant concentration and decreases with increasing temperature, which may be because of structural relaxation processes resulting from molecular rearrangement. All of the estimated parameters have been analysed for their trends with regard to the different patterns of intermolecular interaction present in an aqueous glycyl glycine solution and bio-surfactant system.

Conductometric and Fluorescence Probe Analysis to Investigate the Interaction between Bioactive Peptide and Bile Salts: A Micellar State Study.

The present work deals with the micellar state study of sodium cholate and sodium deoxycholate in the aqueous solution of a bioactive peptide, namely glycyl dipeptide, having different concentrations through conductivity and fluorescence methods at different temperatures. The data obtained from conductivity is plotted against the concentration of Bile salts, and CMC (critical micelle concentration) values are calculated. The results realized have been elucidated with reference to Glycyl dipeptide-bile salts hydrophobic/hydrophilic interactions existing in solution. In addition, the CMC values converted to mole fraction (Xcmc) values have been used to evaluate the standard thermodynamic factors of micellization viz., enthalpy H, free energy ΔGm0, and entropy (ΔSm0) which extract information regarding thermodynamic feasibility of micellar state, energy alteration, and the assorted interactions established in the existing (bile salts-water-glycyl dipeptide) system. Furthermore, the pyrene fluorescence spectrum has also been utilized to study the change in micro polarity induced by the interactions of bile salts with glycyl dipeptide and the aggregation action of bile salts. The decrease in modification in the ratio of intensities of first and third peaks i.e., (I1/I3) for the pyrene molecules in aqueous bile salts solution by the addition of dipeptide, demonstrates that the micelle polarity is affected by glycyl dipeptide. This ratio has also been utilized to determine CMC values for the studied system, and the results have been found to be in good correlation with observations made in conductivity studies.

Scaffolds the backbone of tissue engineering: Advancements in use of polyhydroxyalkanoates (PHA).

Our body is built to heal from inside out naturally but wide-ranging medical conditions necessitate the need for artificial assistance, and therefore, something that can assist the body to heal wounds and damaged tissues quickly and efficiently is of utmost importance. Tissue engineering technology helps to regenerate new tissue to replace the diseased or injured one. The technology uses biodegradable porous three-dimensional scaffolds for mimicking the structure and functions of the natural extracellular matrix. The material and design of scaffolds are critical areas of biomaterial research. Biomaterial-based three-dimensional structures have been the most promising material to serve as scaffolds for seeding cells, both in vivo and in vitro. One such material is polyhydroxyalkanoates (PHAs) which are thermoplastic biopolyesters that are highly suitable for this purpose due to their enhanced biocompatibility, biodegradability, thermo-processability, diverse mechanical properties, non-toxicity and natural origin. Moreover, they have tremendous possibilities of customization through biological physical and chemical modification as well as blending with other materials. They are being used for several tissue engineering applications such as bone graft substitute, cardiovascular patches, stents, for nerve repair and in implantology as valves and sutures. The present review overviews usage of a multitude of PHA-based biomaterials for a wide range of tissue engineering applications, based on their properties suitable for the specific applications.

Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats.

BACKGROUND: Berberine is a natural plant alkaloid and has been reported to possess anti-inflammatory activity. However, berberine's poor bioavailability and low solubility have limited its clinical applicability. Nanoencapsulation of berberine using a suitable carrier can be a promising strategy to improve its efficacy. Therefore, this study aimed to produce berberine-loaded gum nanocomplexes to evaluate their therapeutic effects in a carrageenan-induced rat model. METHODS: Berberine-loaded gum nanocomplexes were prepared by the ionic complexation between the negative charges of the gums (tragacanth and acacia gum) using a cross-linker for loading cationic berberine and their anti-inflammatory activity was evaluated against carrageenan-induced paw edema in rats. ELISA and qRT-PCR were employed to measure the concentration and mRNA expression level of inflammatory mediators in plasma and paw tissue, respectively. RESULTS: Berberine nanocomplexes were characterized for particle size (219.5 nm), zeta potential by the dynamic light scattering (DLS), and for entrapment efficiency (93.2%) Infrared spectroscopy affirmed the loading of berberine in gum nanocomplexes. Transmission electron microscopy of formulation showed the spherical shape of nanocomplexes and small particle size (100-150 nm). Pretreatment of rats with berberine nanocomplexes significantly reduced the paw edema in inflamed rat paws, decreased the production of nitrite and TNF-α in plasma and repressed the mRNA expression levels of TNF-α and IL-1ß in paw tissue in comparison to berberine per se treated rats. CONCLUSION: The obtained berberine-loaded gum nanocomplexes produced a better anti-inflammatory effect as compared to berberine alone and hence can be used as an efficient candidate in the treatment of inflammation. The schematic representation of the preparation of the preparation of berberine-loaded tragacanth/acacia gum nanocomplexes and the evaluation in vivo for anti-inflammatory effects.

Antecedent Metabolic Health and Metformin (ANTHEM) Aging Study: Rationale and Study Design for a Randomized Controlled Trial.

The antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans. While there is extensive epidemiological support for the health benefits of metformin in patient populations, it is not clear if these protective effects apply to those free of age-related disease. Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise. Those who entered the study as insulin-sensitive had no change to detrimental effects while those who were insulin-resistant had positive changes. The objective of this clinical trial is to determine if (a) antecedent metabolic health and (b) skeletal muscle mitochondrial remodeling and function mediate the positive or detrimental effects of metformin monotherapy, independent of exercise, on the metabolism and biology of aging. In a randomized, double-blind clinical trial, adults free of chronic disease (n = 148, 40-75 years old) are stratified as either insulin-sensitive or resistant based on homeostatic model assessment of insulin resistance (≤2.2 or ≥2.5) and take 1 500 mg/day of metformin or placebo for 12 weeks. Hyperinsulinemic-euglycemic clamps and skeletal muscle biopsies are performed before and after 12 weeks to assess primary outcomes of peripheral insulin sensitivity and mitochondrial remodeling and function. Findings from this trial will identify clinical characteristics and cellular mechanisms involved in modulating the effectiveness of metformin treatment to target aging that could inform larger Phase 3 clinical trials aimed at testing aging as a treatment indication for metformin. Clinical Trials Registration Number: NCT04264897.

State of Art Manufacturing and Producing Nanocellulose from Agricultural Waste: A Review.

This review article aims to identify current research areas in nanocellulose production from various agricultural waste materials. In the arena of sustainable materials, nano-sized cellulosic materials have achieved great curiosity from scientists and researchers. Nanocellulose is embellished with some remarkable properties like biodegradability, renewability, low density, low weight, high strength and high stiffness. Nanocellulose is a versatile material and show pertinence towards variety of applications such as heavy metals, pharmaceuticals, medicines, textiles, barrier, reinforcing polymers etc. This review is an effective tool to introduce numerous agricultural waste materials used for the extraction of different forms of nanocellulose viz. cellulose nanofibres and cellulose nanocrystals. The most common preparation methods of nanocellulose are oxidation, high pressure homogenization, refining, electrospinning, steam explosion, acid hydrolysis, enzymatic hydrolysis etc. This review emphasize upon acid hydrolysis as one of the most prominent approach to synthesize nanocellulose by utilizing agricultural waste. This strategy to materialize nanocellulose provides an outlook for the future perspectives in overcoming the global issues like stubble burning, curbing air pollution etc. in a facile manner.

Assessment of Antibacterial Activity of Biosynthesised ZnO Nanoparticles Against Xanthomonas axonopodis pv. malvacearum Causing Bacterial Blight in Cotton.

Cotton (Gossypium hirsutum L.), is an important fibre and oilseed crop of the world. India in particular has the largest area under cotton cultivation and around 60% proportion in the raw fibre textile industry is contributed by cotton alone. Cotton is affected by many diseases (bacterial blights, fungal leafspots, mildew) and pests (white flies, bollworms, aphids etc.). The bacterial blight disease caused by Xanthomonas axonopodis pv. malvacearum is considered as one of the most devastating one that cause huge losses in production every year. Due to systemic spread of this bacterial infection, combating this disease is slightly challenging. Spray of toxic chemicals like endosulfan, streptocycline and dimethoate is a common practice in fields but these chemicals are unable to control the disease spread substantially. Nanotechnology is a newly emerging technology that is being extensively exploited in the agriculture sector these days. Past studies have reported the antimicrobial effect of various metallic nanoparticles including zinc oxide nanoparticles which is known to possess antibacterial potential against both gram +ve and gram -ve bacteria. Based upon this, synthesis of ZnO nanoparticles was carried out using Morus alba plant leaf extract and the nanoparticles were characterised in detail using scanning electron microscopy, atomic force microscopy, X-ray diffraction analysis, electron dispersive X-ray spectroscopy study etc. The zinc oxide nanoparticles were found crystalline in nature and the size ranged between 10-50 nanometers. The efficacy of these nanoparticles was checked against Xanthomonas axonopodis pv. malvacearum under in vitro conditions and found to be very effective in controlling the bacterial spread in comparison to streptomycin that was used as control. Our results suggest that ZnO nanoparticles can be used as an effective antibacterial agent to control bacterial blight disease of cotton.

In Vitro Antifungal and Antibacterial Effects of Biosynthesized Zinc Oxide Nanoparticles Against Selected Pathogenic and Non-Pathogenic Strains.

We have developed a simple, robust environment-friendly and efficient method for ZnO nanoparticles biosynthesis using Dalbergia sissoo fresh leaf extract. Before using these nanoparticles for antimicrobial assay, a detailed characterization was performed using techniques like Ultraviolet/Visible (UV/Vis) spectroscopy, Particle size analysis (PSA), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), atomic force microscopy (AFM),Transmission electron microscopy (TEM) etc. The average size of biosynthesized ZnO nanoparticles was around 30 nm and they were pure and crystalline by nature. The effectiveness of these biosynthesized nanoparticles were checked against both pathogenic and non-pathogenic microbes. A total of eight bacterial strains-Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Klebsilla pneumoniae, Staphylococcus aureus, Streptococcus entericus, Bacillus cereus, Pantoea cypripedii and three fungal strains-Candida albicans, Aspergilus niger and Aspergilus flavus were studied to have a clear view of the spectrum of ZnO nanoparticles anti-microbial activity. The effectiveness of biosynthesized ZnO nanoparticles against the microbes was found to be better than the standard reference antibiotics used (streptomycin, chloramphenicol and rifampicin). The results seem to be very promising and can be used for some practical applications of ZnO nanoparticles in nearfuture.

Utilization of Agricultural Waste from Paddy (Rice) Fields for the Synthesis of Nanocellulose.

Nanotechnology is an interdisciplinary science with multifold applications in various fields. Nanocellulose is an emerging sustainable material possessing marvellous features. It has broad range of prospects in several research areas especially in agriculture sector. This study aims at utilization of agricultural waste of rice (Oryza sativa) from paddy fields viz. rice husk and rice stem into novel commodities i.e., cellulose nanofibres and cellulose nanocrystals. Chemo-mechanical treatment was adopted for successful extraction of cellulose nanofibres from rice stem and cellulose nanocrystals from rice husk. Morphological investigations were accomplished by different microscopic techniques such as atomic force microscopy, scanning electron microscopy and transmission electron microscopy. Fourier transform infrared spectroscopy was employed for identification of attached functional groups. X-ray diffraction study revealed the crystallinity of the synthesized nanocellulose. Thermogravimetric analysis showed the decomposition and degradation of obtained cellulose nanofibres and cellulose nanocrystals. Transmission electron microscopy depicted 50 nm diameter range of cellulose nanofibres of rice stem and atomic force microscopy illustrated 76.77 nm diameter of cellulose nanocrystals of rice husk.

Increased mitochondrial oxygen consumption in adult survivors of preterm birth.

BACKGROUND: Premature birth affects roughly 10% of live births and is associated with long-term increased risk for multiple comorbidities. Although many comorbidities are associated with increased oxidative stress, the potential late impact of extreme premature birth on mitochondrial function has not previously been assessed. We hypothesized that mitochondrial function would be impaired in adult survivors of premature birth. METHODS: Mitochondrial function in peripheral blood mononuclear cells from young adults born moderately to extremely preterm was measured using a Seahorse XF Analyzer at baseline and in response to acute oxidative stress, and compared to age-matched term-born adults. Adult pulmonary function was also obtained. RESULTS: Young adults born preterm (average gestational age 29 weeks) had increased mitochondrial oxygen consumption at baseline, particularly with respect to basal and non-ATP-linked respiration. Maximal and spare capacities were also higher, even in response to acute oxidative stress. Lung function was lower in adults born preterm, and the degree of airflow obstruction correlated only modestly with mitochondrial function. CONCLUSIONS: In conclusion, adults born preterm have higher basal and non-ATP-linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm. IMPACT: Adults born preterm have higher maximal but also higher basal and non-ATP-linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm. Prior studies demonstrate a link between perinatal mitochondrial function and risk for development of bronchopulmonary dysplasia. Here, maximal mitochondrial respiration correlates modestly with adult lung function. Peripheral blood mononuclear cell mitochondrial function may be a biomarker of both early lung function and late cardiometabolic risk after preterm birth.

Estrogen receptor-α prevents right ventricular diastolic dysfunction and fibrosis in female rats.

Although women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Estrogen receptor-α (ERα) has been identified as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains poorly understood. We hypothesized that loss of functional ERα removes female protection from adverse remodeling and is permissive for the development of a maladapted RV phenotype. Male and female rats with a loss-of-function mutation in ERα (ERαMut) and wild-type (WT) littermates underwent RV pressure overload by pulmonary artery banding (PAB). At 10 wk post-PAB, WT and ERαMut demonstrated RV hypertrophy. Analysis of RV pressure waveforms demonstrated RV-pulmonary vascular uncoupling and diastolic dysfunction in female, but not male, ERαMut PAB rats. Similarly, female, but not male, ERαMut exhibited increased RV fibrosis, comprised primarily of thick collagen fibers. There was an increased protein expression ratio of TIMP metallopeptidase inhibitor 1 (Timp1) to matrix metalloproteinase 9 (Mmp9) in female ERαMut compared with WT PAB rats, suggesting less collagen degradation. RNA-sequencing in female WT and ERαMut RV revealed kallikrein-related peptidase 10 (Klk10) and Jun Proto-Oncogene (Jun) as possible mediators of female RV protection during PAB. In summary, ERα in females is protective against RV-pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. ERα appears to be dispensable for RV adaptation in males. ERα may be a mediator of superior RV adaptation in female patients with PAH.NEW & NOTEWORTHY Using a novel loss-of-function mutation in estrogen receptor-α (ERα), we demonstrate that female, but not male, ERα mutant rats display right ventricular (RV)-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload, indicating a sex-dependent role of ERα in protecting against adverse RV remodeling. TIMP metallopeptidase inhibitor 1 (Timp1), matrix metalloproteinase 9 (Mmp9), kallikrein-related peptidase 10 (Klk10), and Jun Proto-Oncogene (Jun) were identified as potential mediators in ERα-regulated pathways in RV pressure overload.

Removal of Pb (II) from aqueous solution using nanoadsorbent of Oryza sativa husk: Isotherm, kinetic and thermodynamic studies.

This research focus on the removal of Pb (II) ions from aqueous solution by adsorption process using nanoadsorbent developed from agricultural waste Oryza sativa husk (OSH). Surface morphology of nanoadsorbent was analyzed by FE-SEM, elemental composition by EDX and size by AFM. Attachment of functional groups on nanoadsorbent was determined by FTIR. The effect of pH, dose, contact time, initial concentration and temperature were investigated. Optimum adsorption of lead at pH 8, contact time 70 min at 60 °C temperature with 0.6 g/50 mL nanoadsorbent dose obeyed pseudo second order kinetic model with R2 0.996. Pb (II) adsorption was analyzed by Freundlich, Langmuir and Temkin models. Freundlich isotherm model with correlation coefficient R2 0.999 was best fitted. Thermodynamic parameters anticipated the adsorption process to be endothermic and spontaneous. Post adsorption elution was carried out successfully. Results demonstrate that OSH is a low cost and eco-friendly choice for Pb (II) remediation.

Bimodal right ventricular dysfunction after postnatal hyperoxia exposure: implications for the preterm heart.

Rats exposed to postnatal hyperoxia develop right ventricular (RV) dysfunction, mild pulmonary hypertension, and dysregulated cardiac mitochondrial biogenesis when aged to one year, with the degree of cardiac dysfunction and pulmonary hypertension similar to that previously described in young adults born preterm. Here, we sought to understand the impact of postnatal hyperoxia exposure on RV hemodynamic and mitochondrial function across the life span. In Methods, pups from timed-pregnant Sprague-Dawley rats were randomized to normoxia or hyperoxia [fraction of inspired oxygen (FIO2), 0.85] exposure for the first 14 days of life, a commonly used model of chronic lung disease of prematurity. RV hemodynamic and mitochondrial function were assessed by invasive measurement of RV pressure-volume loops and by high-resolution respirometry at postnatal day 21 (P21), P90, and P365. In Results, at P21, hyperoxia-exposed rats demonstrated severe pulmonary hypertension and RV dysfunction, accompanied by depressed mitochondrial oxidative capacity. However, significant upregulation of mitochondrial biogenesis at P21 as well as improved afterload led to complete RV hemodynamic and mitochondrial recovery at P90. Mitochondrial DNA mutations were significantly higher by P90 and associated with significant late RV mitochondrial and hemodynamic dysfunction at P365. In conclusion, there appears to be a "honeymoon period" where cardiac hemodynamic and mitochondrial function normalizes following postnatal hyperoxia exposure, only to decline again with ongoing aging. This finding may have significant implications if a long-term pulmonary vascular screening program were to be developed for children or adults with a history of severe prematurity. Further investigation into the mechanisms of recovery are warranted.NEW & NOTEWORTHY Premature birth is associated with increased risk for cardiac dysfunction and failure throughout life. Here, we identify bimodal right ventricular dysfunction after postnatal hyperoxia exposure. Mitochondrial biogenesis serves as an early adaptive feature promoting recovery of cardiac hemodynamic and mitochondrial function. However, the accumulation of mitochondrial DNA mutations results in late mitochondrial and right ventricular dysfunction. This bimodal right ventricular dysfunction may have important implications for the development of screening programs in the preterm population.

In vitro anti-inflammatory and antioxidant potential of thymol loaded bipolymeric (tragacanth gum/chitosan) nanocarrier.

Thymol is a natural bioactive agent which possesses various medicinal properties like antimicrobial, antifungal, anti-inflammatory, anticancer etc. and has been widely used in traditional medicine and food industries. It is eco-friendly, cheap, nontoxic and has been granted generally recognized as safe (GRAS) notation by USFDA. Its use is somewhat muted due to drawbacks like lesser bioavailability, comparatively poor solubility and low susceptibility to oxidation. In the present work, nanoformulation of thymol was prepared by ionic complexation of tragacanth gum and chitosan. Chitosan of different concentrations was used to obtain desired particle size and encapsulation efficiency. It was noted that a ratio of 1:2 (tragacanth gum:chitosan) yielded a minimum particle size along with higher encapsulation efficiency. Morphology of these optimized nanoparticles was found to be spherical using TEM. These particles were found in the size range of 150-200 nm. Further comparative study of the prepared nanoformulation and thymol for antioxidant and anti-inflammatory efficacy was done using DPPH method and HRBC (Human red blood cell) stabilization method. The results suggested an increase in both anti-inflammatory and antioxidant activity of thymol nanoformulation. This study will open up new avenues for application in the field of food and pharmaceutical industries.

Correction: An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

Correction for 'An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling' by Santosh Kumari et al., Org. Biomol. Chem., 2018, 16, 3220-3228.

An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

An efficient, one-pot Cu-catalyzed tandem synthesis of fluorescent 1-benzyl-2-phenyl-1,2-dihydro-5H-chromeno[4,3-d]pyrimidin-5-ones from 4-chloro-3-formylcoumarin and benzylamines was developed by in situ intramolecular cross-dehydrogenative C(sp3)-N bond formation in moderate-to-good yields under ligand-free ambient conditions. This synthesis was easily scalable, and the generality of the substrates was established. These coumarin-fused pyrimidines exhibited interesting photo-physical properties and high quantum yields, and would be potential candidates for facilitating suitable studies in medicinal chemistry and materials science.

Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways.

Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium.