Ellagic acid regulates hyperglycemic state through modulation of pancreatic IL-6 and TNF- α immunoexpression

BackgroundType 2 diabetes (T2DM) is a chronic metabolic disorder. Although therapeutic pharmaceutical agents continue to advance, herbal medicines are potential complementary treatments for the promotion of glucose homeostasis, with minimal adverse effects. Conventionally, ellagic acid (EA) has been utilized for the therapy of a range of pathologies owing to its anti-inflammatory and anti-diabetic actions.ObjectiveThe aim of this study is to determine the activity of EA on serum α-amylase and lipase titers, and on pancreatic tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and interleukin-6 (IL-6) concentrations using the streptozocin-induced T2DM rodent model.MethodsEA extract synthesized from fresh strawberry fruit was employed for therapy. 50 adults male Wistar rats were randomized into either control, EA, diabetic, co-treated or post- treated cohorts.ResultsEA diminished fasting blood glucose levels, altered lipase, amylase, IL-6, PCNA and TNF- α expression and enhanced islet cell renewal, insulin, and immunoreactivities.ConclusionInflammatory indicators are elevated in the presence of T2DM. Extract of EA has overall tissue reparative and safeguarding properties, as indicated by the augmented β- cell population and enhanced glucose homeostasis. Thus, EA may be an innovative treatment approach for the maintenance of normoglycemia in individuals with T2DM.     

Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via Nanostructured Lipid Carrier (NLC) Formulation

Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but unfortunately with poor bioavailability. Aiming to improve its poor oral bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by high-speed homogenization followed by ultrasonication and evaluated in vitro. Bioavailability and pharmacodynamic studies were also performed. The resultant NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system which consequently produced larger particle size and polydispersity index, smaller zeta potential values, and lower short-term (30 days) physical stability than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6?±?5% and 96.2?±?1.6%. TQ AUC_0–t values were higher in animals treated with NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12, respectively) higher than TQ suspension, indicating bioavailability enhancement by NLC formulation. Hepatoprotective effects of F12 showed significant (P?<?0.05) decrease in both serum alanine amino transferase and aspartate amino transferase to reach 305.0?±?24.88 and 304.7?±?23.55 U/ml, respectively, when compared with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P?<?0.05) decline of malondialdehyde and elevation of reduced glutatione. This improvement was also confirmed histopathologically.     

Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design,synthesis, molecular docking studies and ADMET prediction

Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.     

Isolation and characterization of acetonitrile utilizing bacteria

Summary Bacteria utilizing high concentrations of acetonitrile as the sole carbon source were isolated and identified asChromobacterium sp. andPseudomonas aeruginosa. Maximum growth was attained after 96 h of incubation andP. aeruginosa grew slightly faster thanChromobacterium sp. The strains were able to grow and oxidize acetonitrile at concentrations as high as 600 mM. However, higher concentrations inhibited growth and oxygen uptake. Degradation studies with (¹⁴C)acetonitrile indicated 57% of acetonitrile was degraded byPseudomonas aeruginosa as compared to 43% byChromobacterium. The isolates utilized different nitrile compounds as carbon substrates.     

Pervasive gene conversion in chromosomal inversion heterozygotes

Chromosomal inversions shape recombination landscapes, and species differing by inversions may exhibit reduced gene flow in these regions of the genome. Though single crossovers within inversions are not usually recovered from inversion heterozygotes, the recombination barrier imposed by inversions is nuanced by noncrossover gene conversion. Here, we provide a genomewide empirical analysis of gene conversion rates both within species and in species hybrids. We estimate that gene conversion occurs at a rate of 1 × 10^–5 to 2.5 × 10^–5 converted sites per bp per generation in experimental crosses within Drosophila pseudoobscura and between D. pseudoobscura and its naturally hybridizing sister species D. persimilis. This analysis is the first direct empirical assessment of gene conversion rates within inversions of a species hybrid. Our data show that gene conversion rates in interspecies hybrids are at least as high as within‐species estimates of gene conversion rates, and gene conversion occurs regularly within and around inverted regions of species hybrids, even near inversion breakpoints. We also found that several gene conversion events appeared to be mitotic rather than meiotic in origin. Finally, we observed that gene conversion rates are higher in regions of lower local sequence divergence, yet our observed gene conversion rates in more divergent inverted regions were at least as high as in less divergent collinear regions. Given our observed high rates of gene conversion despite the sequence differentiation between species, especially in inverted regions, gene conversion has the potential to reduce the efficacy of inversions as barriers to recombination over evolutionary time.     

Disturbance-dependent Yellow-legged Gull (Larus michahellis) predation on Larid chicks decreases with chick age

Predation is one of the key factors shaping the dynamics of animal populations. In birds, nest loss due to predation can be a significant cause of low reproductive success. Ground-nesting birds are among the bird groups most susceptible to predation, mainly because their nests are easily accessible to a broad suite of potential predators. For these birds, anthropogenic disturbances can generate changes in nest predation risk by altering their antipredator behaviour and also by altering the behaviour of the predator species, i.e. the predator becoming much more aware of predation opportunities due to frequent disturbances and/or motivated to repeat predation attempts when some are successful. To date, most previous studies investigating this have focused on a single effect, either predation or disturbance, on chick survival. It remains unknown how the risk of predation with and without disturbance varies with chick age. In this study, we used behavioural observations to assess how the interaction between predators and disturbance affects predation risk in chicks and how this interacts with chick age. Specifically, we investigated the effect of disturbance caused by humans and stray dogs on the predation of Slender-billed Gull Chroicocephalus genei chicks by Yellow-legged Gulls Larus michahellis, and whether this depended on the age of the chicks. Our results revealed that disturbance had a significant positive effect on predation measures of Slender-billed Gull chicks by Yellow-legged Gulls, but that this effect was mediated both by disturbance type and the age of chicks. Stray dogs entering the colony had a stronger disturbance effect on chicks than passing humans, increasing predation risk by Yellow-legged Gulls. Our results also showed that chick age interacts with disturbance type to determine the predation risk. This is probably mediated by chicks' capacity to escape predation by gathering in a single large crèche that runs into the water when disturbed. To preserve Slender-billed Gull colonies in one of its few remaining breeding sites in Tunisia, and as gulls tend to react even when the disturbance occurs relatively far from the colonies, it is crucial to (1) restrict human access to dikes and islets where large colonies breed and (2) construct artificial islets attractive to gulls and inaccessible to stray dogs.     

Malyngamide 4, a new lipopeptide from the Red Sea marine cyanobacterium Moorea producens (formerly Lyngbya majuscula)

In our continuing effort to discover new drug leads from Red Sea marine organisms, a sample of the marine cyanobacterium Moorea producens (previously Lyngbya majuscula) was investigated. Bioassay-directed purification of a tumor cell-growth inhibitory fraction of the organic extract of the Red Sea cyanobacterium afforded a new compound, malyngamide 4 (1), together with five previously reported compounds, malyngamide A (2) and B (3), (S)-7-methoxytetradec-4(E)-enoic acid (lyngbic acid, 4), aplysiatoxin (5) and debromoaplysiatoxin (6). Assignment of the planar structures of these compounds was based on extensive analysis of one- and two-dimensional NMR spectra and high-resolution mass spectrometric data. The isolated compounds were evaluated for their inhibitory activity against three cancer cell lines. In addition, the antibacterial activity of the compounds against Mycobacterium tuberculosis H₃₇Rv ATCC 27294 (H₃₇Rv) was evaluated. Lyngbic acid (4) was the most active against M. tuberculosis, while malyngamides 4 (1) and B (3) moderately inhibited the cancer cell lines. The other compounds were deemed inactive at the test concentrations.     

Emerging perspectives in store-operated Ca2+ entry: roles of Orai, Stim and TRP

Depletion of intracellular Ca2+ stores induces Ca2+ influx across the plasma membrane through store-operated channels (SOCs). This store-operated Ca2+ influx is important for the replenishment of the Ca2+ stores, and is also involved in many signaling processes by virtue of the ability of intracellular Ca2+ to act as a second messenger. For many years, the molecular identities of particular SOCs, as well as the signaling mechanisms by which these channels are activated, have been elusive. Recently, however, the mammalian proteins STIM1 and Orai1 were shown to be necessary for the activation of store-operated Ca2+ entry in a variety of mammalian cells. Here we present molecular, pharmacological, and electrophysiological properties of SOCs, with particular focus on the roles that STIM1 and Orai1 may play in the signaling processes that regulate various pathways of store-operated entry.     

The Clinical Characteristics and Pathological Patterns of Postinfectious Glomerulonephritis in HIV-Infected Patients

Background

Postinfectious glomerulonephritis (PIGN), a form of immune complex GN, is not well-defined in HIV-infected patients. This study characterizes PIGN in this patients’ population and determine the impact of histopathological patterns on renal outcome and mortality.

Methods

HIV-infected patients with PIGN from September 1998 to July 2013 were identified. Archived slides were reviewed by a blinded renal pathologist, classified into acute, persistent and healed PIGN. Groups were compared using Wilcoxon rank-sum and Fisher’s exact test. Survival analyses were performed to determine association of histopathological pattern with renal outcome and mortality.

Results

Seventy-two HIV-infected predominantly African American males were identified with PIGN. Median (interquartile range) age and creatinine at the time of renal biopsy was 48 years (41, 53) and 2.5 mg/dl (1.5, 4.9) respectively. Only 2 (3%) had acute PIGN, 42 (58%) had persistent PIGN and 28 (39%) had healed PIGN. Three patients (4%) had IgA-dominant PIGN. Only 46% of the patients had confirmed positive cultures with Staphylococcus the most common infectious agent. During a median follow up of 17 months, the pathological pattern had no impact on renal outcome (P = 0.95). Overall mortality was high occurring in 14 patients (19%); patients with healed PIGN had significantly increased mortality (P = 0.05).

Conclusion

In HIV-infected patients, Staphylococcus is the most common cause of PIGN. Renal outcome was not influenced by the histopathological pattern but those with healed PIGN had greater mortality which was potentially due to a confounder not accounted for in the study.