Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients

Vitamin D3 deficiency, obesity, and diabetes mellitus (DM) have been shown to increase the risk of cardiovascular diseases (CVDs). However, the early detection of vascular damage in those patients is still difficult to ascertain. MicroRNAs (miRNAs) are recognized to play a critical role in initiation and pathogenesis of vascular dysfunction. Herein, we aimed to identify circulating miRNA biomarkers of vascular dysfunction as early predictors of CVDs. We have recruited 23 middle-aged Emiratis patients with the following criteria: A healthy control group with vitamin D ≥ 20ng, and BMI 1.5) in high-risk patients for CVDs vs healthy controls. Collectively, our result indicates that four specific circulating miRNA signature, may be utilized as non-invasive, diagnostic and prognostic biomarkers for early vascular damage in patients suffering from vitamin D deficiency, obesity and DM

Comparative profiling of biomarker psoralen in antioxidant active extracts of different species of genus Ficus by validated HPTLC method

Background: A simple but sensitive HPTLC method was developed for the comparative evaluation of psoralen in antioxidant active extracts of leaves of five different species of genus Ficus (Ficus carica, Ficus nitida, Ficus ingens, Ficus palmata and Ficus vasta).Materials and Methods: HPTLC studies were carried out using CAMAG HPTLC system on Glass-backed silica gel 60F254 HPTLC pre-coated plates using selected mobile phase toluene: methanol (9:1). The antioxidant activity was carried out, using DPPH free radical method.Results: Among all the five species of genus Ficus, F. palmata and F. carica exhibited comparatively good antioxidant activity in DPPH assay. The developed HPTLC method was found to give a compact spot for psoralen (Rf = 0.55±0.001) at 305 nm. The regression equation and r2 for psoralen was found to be Y= 4.516X+35.894 and 0.998. The quantification result revealed the presence of psoralen in only two species, F. carica (0.24%, w/w) and F. palmata (1.88%, w/w) which supported their supremacy for anti-oxidant potential over other species. The statistical analysis proved that the developed method was reproducible and selective.Conclusion: The developed method can be used as an important tool to assure the therapeutic dose of active ingredients in herbal formulations as well as for standardization and quality control of bulk drugs and in-process formulations. This method can also be employed for the further study of degradation kinetics and determination of psoralen in plasma and other biological fluids.Key words: Ficus species, psoralen, antioxidant, HPTLC, Validation

Synthesis of some new propanamide derivatives bearing 4- piperidinyl-1,3,4-oxadiazole, and their evaluation as promising anticancer agents

Purpose: To sequentially synthesize piperidine-4-carboxylic acid ethyl ester-appended 1,3,4-oxadiazole hybrids and to evaluate them as anticancer agents.Methods: Ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidinecarboxylate (1) was synthesized from 4- methylbenzenesulfonylchloride (a) and ethyl 4-piperidinecarboxylate (b). Compound (1) was converted into ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidine carbohydrazides (2) and 5-{1-[(4- methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) respectively. A variety of aryl amine (4a-l) were treated with 2-bromopropionylbromide to synthesize an array of propanamide (5a-l). Finally, 5-{1-[(4-methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) and propanamides (5a-l) were reacted to synthesize target compounds (6a-l). Purity compounds 6a-l was confirmed by spectroscopic techniques like (1H-NMR), (13C-NMR) and EI-MS. To determine their anticancer potential, the change in absorbance of mixture and cell line before and after incubation was determined.Results: All the compounds 6a-l were successfully synthesized in 73-85 % yield. Compounds 6h, 6j and 6e have low IC50 (±SD) values of 20.12 ± 6.20, 10.84 ± 4.2 and 24.57 ± 1.62 μM to act as strong anticancer agents relative to doxorubicin (0.92 ± 0.1 μM) used as a reference.Conclusion: The synthesized propanamide derivatives bearing 4-piperidinyl-1,3,4-oxadiazole are potential anticancer agents, but further studies, especially in vivo, are required to ascertain their therapeutic usefulness.Keywords: Ethyl isonipecotate, Propanamides, 1,3,4-Oxadiazole, Anti-cancer activit

Tuberous sclerosis with visceral leishmaniasis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment.</p> <p>Case presentation</p> <p>A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics.</p> <p>Conclusion</p> <p>The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.</p

The migration-sustainability paradox: transformations in mobile worlds

This is the final version. Available from Elsevier via the DOI in this record. Migration represents a major transformation of the lives of those involved and has been transformative of societies and economies globally. Yet models of sustainability transformations do not effectively incorporate the movement of populations. There is an apparent migration-sustainability paradox: migration plays a role as a driver of unsustainability as part of economic globalisation, yet simultaneously represents a transformative phenomenon and potential force for sustainable development. We propose criteria by which migration represents an opportunity for sustainable development: increasing aggregate well-being; reduced inequality leading to diverse social benefits; and reduced aggregate environmental burden. We detail the dimensions of the transformative potential of migration and develop a generic framework for migration-sustainability linkages based on environmental, social, and economic dimensions of sustainability, highlighting identity and social transformation dimensions of migration. Such a model overcomes the apparent paradox by explaining the role of societal mobility in achieving sustainable outcomes.Economic and Social Research Council (ESRC)European Research CouncilUniversity of Exeter European Network Fun

The Migration-Sustainability Paradox: Transformations in Mobile Worlds

Migration represents a major transformation of the lives of those involved and has been transformative of societies and economies globally. Yet models of sustainability transformations do not effectively incorporate the movement of populations. There is an apparent migration-sustainability paradox: migration plays a role as a driver of unsustainability as part of economic globalisation, yet simultaneously represents a transformative phenomenon and potential force for sustainable development. We propose criteria by which migration represents an opportunity for sustainable development: increasing aggregate well-being; reduced inequality leading to diverse social benefits; and reduced aggregate environmental burden. We detail the dimensions of the transformative potential of migration and develop a generic framework for migration-sustainability linkages based on environmental, social, and economic dimensions of sustainability, highlighting identity and social transformation dimensions of migration. Such a model overcomes the apparent paradox by explaining the role of societal mobility in achieving sustainable outcomes

Blackcurrants: A Nutrient-Rich Source for the Development of Functional Foods for Improved Athletic Performance

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordBlackcurrants are nutrient-rich fruits with a significant amount of bioactive compounds including vitamin C and polyphenols, especially anthocyanins. The high phytochemical content of blackcurrants promotes this fruit to become a valuable functional food ingredient with varying health-promoting activities targeting different consumers including athletes. Athletes experience oxidative stress during intense exercise, which can result in inflammation and reduced exercise performance. Antioxidants such as vitamin C and polyphenols can restore the regular oxidative status of the body. Blackcurrant supplementation has shown potential ergogenic activity to improve athlete performance during high-intensity training. Clinical trials have evaluated the effectiveness of blackcurrant supplementation on exercise performance, fat oxidation, blood lactate levels, muscle fatigue, and cardiac output. Due to the rich nutritional value of blackcurrants, they can be a potential candidate for the development of functional foods targeted at the improved performance of athletes. Blackcurrants can be used as ingredients to develop functional beverages and snacks for athletes as well as gluten-free products for celiac athletes.Blackcurrant is rich in bioactive compounds that can help improve athletic performance. It can be considered a potential bioactive ingredient to develop functional foods for athletes

Structural studies of Schiff-base [2 + 2] macrocycles derived from 2,2′-oxydianiline and the ROP capability of their organoaluminium complexes

The molecular structures of a number of solvates of the [2 + 2] Schiff-base macrocycles {[2-(OH)-5-(R)-C6H2-1,3-(CH)2][O(2-C6H4N)2]}2 (R = Me L1H2, tBu L2H2, Cl L3H2), formed by reacting 2,6-dicarboxy-4-R-phenol with 2,2′-oxydianiline (2-aminophenylether), (2-NH2C6H4)2O, have been determined. Reaction of LnH2 with two equivalents of AlR′3 (R′ = Me, Et) afforded dinuclear alkylaluminium complexes [(AlR′2)2L1–3] (R = R′ = Me (1), R = tBu, R′ = Me (2), R = Cl, R′ = Me (3), R = Me, R′ = Et (4), R = tBu, R′ = Et (5), R = Cl, R′ = Et (6)). For comparative studies, reactions of two equivalents of AlR′3 (R′ = Me, Et) with the macrocycle derived from 2,2′-ethylenedianiline and 2,6-dicarboxy-R-phenols (R = Me L4H2, tBu L5H2) were conducted; the complexes [(AlMe)(AlMe2)L5]·2¼MeCN (7·2¼MeCN) and [(AlEt2)2L4] (8) were isolated. Use of limited AlEt3 with L3H2 or L5H2 afforded mononuclear bis(macrocyclic) complexes [Al(L3)(L3H)]·4toluene (9·4toluene) and [Al(L5)(L5H)]·5MeCN (10·5MeCN), respectively. Use of four equivalents of AlR′3 led to transfer of alkyl groups and isolation of the complexes [(AlR′2)4L1′–3′] (R = L2′, R′ = Me (11); L3′, R′ = Me (12); L1′, R′ = Et (13); L2′, R′ = Et (14); L3′, R′ = Et (15)), where L1′–3′ is the macrocycle resulting from double alkyl transfer to imine, namely {[2-(O)-5-(R)C6H2-1-(CH)-3-C(R′)H][(O)(2-(N)-2′-C6H4N)2]}2. Molecular structures of complexes 7·2¼MeCN, 8, 9·4toluene, 10·5MeCN and 11·1¾toluene·1¼hexane are reported. These complexes act as catalysts for the ring opening polymerisation (ROP) of ε-caprolactone and rac-lactide; high conversions were achieved over 30 min at 80 °C for ε-caprolactone, and 110 °C over 12 h for rac-lactide

Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records

Background: Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored.Methods: Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and adjusted effect of the variants on statin efficacy.Results: Around 9,401 statin users met study inclusion criteria, of whom 8,843 were first prescribed simvastatin or atorvastatin. The average difference in post-treatment compared to pre-treatment non-HDL-cholesterol was 1.45 (+/- 1.04) mmol/L. In adjusted analyses, only two variants, one in the gene ATP-binding cassette transporter B1 (ABCB1; rs1045642), and one in leukocyte immunoglobulin like receptor B5 (LILRB5; rs12975366), were associated with statin efficacy. In ABCB1, homozygous carriers of the C allele at rs1045642 had 0.06mmol/L better absolute reduction in non-HDL-cholesterol than carriers of the T allele (95% CI: 0.01, 0.1). In LILRB5 (rs12975366), carriers of the C allele had 0.04mmol/L better absolute reduction compared to those homozygous for the T allele (95% CI: 0.004, 0.08). When combined into a two-variant risk score, individuals with both the rs1045642-CC genotype and the rs12975366-TC or CC genotype had a 0.11mmol/L greater absolute reduction in non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI: 0.05, 0.16; pConclusion: We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users.</p