Fusarithioamide B,a new benzamide derivative from the endophytic fungus Fusarium chlamydosporium with potent cytotoxic and antimicrobial activities

Fusarithioamide B (6), a new aminobenzamide derivative with unprecedented carbon skeleton and five known metabolites: stigmast-4-ene-3-one (1), stigmasta-4,6,8(14),22-tetraen-3-one (2), p-hydroxyacetophenone (3), tyrosol (4), and fusarithioamide A (5) were separated from Fusarium chlamydosporium EtOAc extract isolated from Anvillea garcinii (Burm.f.) DC. leaves (Asteraceae). The structure elucidation and complete assignment of the isolated metabolites were performed mainly by the aid of various NMR and MS data. Fusarithioamide B (6) has been assessed for antibacterial and antifungal activities towards various microbial strains by disc diffusion assay. It exhibited selective antifungal activity towards C. albicans (MIC 1.9?µg/ml and IZD 14.5?mm), comparing to clotrimazole (MIC 2.8?µg/ml and IZD 17.9?mm). Also, it possessed high antibacterial potential towards E. coli, B. cereus, and S. aureus compared to ciprofloxacin. Furthermore, 6 was tested for the in vitro cytotoxic effect against KB, HCT-116, BT-549, MCF-7, SKOV-3, and SK-MEL cell lines. It had selective and potent effect towards BT-549, MCF-7, SKOV-3, and HCT-116 cell lines with IC₅₀s 0.09, 0.21, 1.23, and 0.59?μM, respectively compared to doxorubicin (IC₅₀s 0.046, 0.05, 0.321, and 0.24?μM, respectively). Fusarithioamide B may provide a lead molecule for future developing of antitumor and antimicrobial agents.     

Checks and Balances between Autophagy and Inflammasomes during Infection

Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the cysteine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.     

A Peptide Based Pro-drug Disrupts Alzheimer’s Amyloid into Non-toxic Species and Reduces Aβ Induced Toxicity In Vitro

Aggregation of Amyloid β (Aβ) in the interneuronal spaces is a major etiopathological factor for onset and progression of Alzheimer’s disease (AD). Since the mechanism of aggregation is not fully understood, control and modulation of the aggregation process is a challenging task. Although, several strategies were developed for the past few decades, yet there is no proper therapeutics available. Herein, we report a peptide based pro-drug, termed as a conformational Pro-Drug peptide (PDp), which disrupts existing Aβ fibrils, but does not produce toxic soluble oligomers, through a series of spontaneous chemical reactions resulting in in situ generation of β-sheet destabilizing factors. Furthermore, PDp reduces Aβ mediated toxicity examined on an in vitro model consisting of the human neuroblastoma SH-SY5Y cells. PDp also disrupts fibrils originated from AD affected human cerebrospinal fluid. These findings will help to understand the process of amyloidogenesis better and also indicate a novel approach for therapeutically important peptide design.     

Niosomes for oral delivery of nateglinide: in situ–in vivo correlation

Niosomes have been claimed to enhance intestinal absorption and to widen the absorption window of acidic drugs. This was reported after monitoring the intestinal absorption in situ. Accordingly, the aim of this work was to investigate the effect of niosomal encapsulation on intestinal absorption and oral bioavailability of nateglinide. This was conducted with the goal of correlation between in situ intestinal absorption and in vivo availability. The drug was encapsulated into proniosomes. The niosomes resulting after hydration of proniosomes were characterized with respect to vesicle size and drug entrapment efficiency. The in situ rabbit intestinal absorption of nateglinide was monitored from its aqueous solution and niosomes. Streptozotocin was used to induce diabetes in albino rats which were then used to assess the hypoglycemic effect of nateglinide after oral administration of aqueous dispersion and niosomal systems. The prepared vesicles were in the nanoscale with the recorded size being 283?nm. The entrapment efficiency depended on the pH of the formulation. The in situ intestinal absorption reflected non-significant alteration in the membrane transport parameters of the drug after niosomal encapsulation compared with the free drug solution. In contrast, niosomes showed significant improvement in the rate and extent of the hypoglycemic effect compared with the unprocessed drug. This discrepancy can be attributed to different transport pathway for the drug after niosomal inclusion with the vesicles undergoing translymphatic transport which can minimize presystemic metabolism. However, this requires confirmatory investigations. In conclusion niosomes can enhance oral bioavailability of nateglinide with the absorption being through nontraditional pathway.     

The psychoactive substance of cannabis Δ9-tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells

Background

Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function.

Epidemiological characterization of serotype group B Streptococci neonatal infections associated with interleukin-6 level as a sensitive parameter for the early diagnosis

Group B streptococcal infection (Streptococcus agalactiae) is one of the leading causes of life-threatening disease in the early neonatal period, resulting in sepsis, pneumonia, and meningitis. During invasive infections, an excessive release of pro-inflammatory cytokine, such as interleukin-6 (IL-6), thus IL-6 gene is significant, as a diagnostic marker of systemic infection of the newborns. The present study aimed to describe the epidemiology diagnostic of GBS disease in neonatal by phenotypic and genotypic methods. Nine hundred and ninety-six samples were taken at Maternity and Children Hospital, Jeddah, Saudi Arabia for a period of one year (2011–2012). Results indicated that out of 217 infected samples, twenty (9.23.0%) were positive for group B Streptococci bacteria. This study also shows that female infants are more susceptible than males. The level of IL-6 was higher in mothers above 30 years. Twenty positive Streptococci group B isolates showed bands with the cylE gene primers in the border between 228 bp, 267 bp and 50 bp. Molecular detection by Real time polymerase chain reaction was also done to detect the target (Sip gene) encoding the Sip surface immunogenic protein. Specific primers and TaqMan probe were chosen for this purpose. A Real-time PCR method targeting the sip gene of GBS in neonates after delivery has been evaluated.     

Impact of Prenatal and Postnatal Treatment of Sodium Fluoride and Aluminum Chloride on Some Hormonal and Sensorimotor Aspects in Rats

In most communities, there is a constant exposure to environmental pollutants with probable negative impact on the development of the nervous system. Among these pollutants are the sodium fluoride (NaF) and aluminum chloride (AlCl₃) which may represent a real threat to the proper functioning of the brain. This study comprises two fundamentally different strategies; in the first one, pregnant rats were administered a daily dose of NaF (0.15 g /L) or AlCl₃ (500 mg/L) in the drinking water either separately or in combination with each other from day 6 of gestation until just after weaning. In the second approach, the male rats born to mothers exposed to the pollutants were divided into two groups. In the first, rats were continued to be treated with the same pollutants administered to them in the drinking water at the same dose level until the age of 70 days. The rats of the second group were supplied with drinking water without either one of the pollutants for a similar period of time. The rats exposed to NaF separately or in combination with AlCl₃ during the prenatal life and subsequently through the postnatal stages exhibited disturbance in the locomotor activities. This was concomitant with alterations in plasma, PTH, ACTH, and estradiol levels. Additionally, the serum levels of LH and testosterone were altered in the two groups treated with sodium fluoride during the prenatal and up to the weaning periods or in the group which continued to have the NaF until day 70 after birth.     

Foliar application of the triterpene derivative 24-methylen-elemo-lanosta-8,24-dien-3-one alleviates salt toxicity in grapevine

This work focused on the effect triterpene derivative 24-methylen-elemo-lanosta-8,24-dien-3-one (F3) on the induction of salt stress tolerance of the Moroccan grapevine cv. “Doukkali”. Hardwood cuttings of the grapevine from a homogeneous plant material collected in the field were grown in hydroponic medium under different salt concentrations and treated with 50 or 100 µg ml^?1 of F3. Salt stress affected several physiological and biochemical parameters including relative water content, chlorophyll a and b content, peroxidase, and polyphenol oxidase activities, which decreased along with time. Meanwhile, proline, proteins, soluble sugars, H₂O₂, and carotenoid content, as well as phenolic compound content increased, suggesting an evidence of tolerance of this local variety to salinity. An exogenous supply of the triterpenic product increased all these parameters under normal conditions. In addition, F3 at low dose was found to be successful in lowering Na⁺ content and alleviating the inhibitory effects of salt stress on relative water content as well as on chlorophyll a and b.