Synthesis,characterization, and anticancer evaluation of novel 4-hydrazinothiazole analogs

Single-step synthesis of novel 4-hydrazinothiazole derivatives 6a–e was achieved under mild conditions using the sequential four-components method involving isothiocyanate, aminoguanidine, carbonyl adduct, and α-haloketone derivatives. Deprotection of these hydrazinothiazoles was influenced by acylation, providing a novel group of diacylated molecular structures with a broader scope for the design of thiazolyl-containing drugs 7a and 7b . FTIR, ¹H/¹³C NMR, LC–MS spectroscopy, and CHN elemental analyses were used to study the compound chemical structures. Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human periodontal ligament fibroblast (HPDLF) cells, the 4-hydrazinothiazole derivatives were screened for cytotoxicity in an in vitro cytotoxicity investigation. The 4-hydrazinothiazole compound 6b bearing an isopropylidene-hydrazino group demonstrated strongly potent cytotoxicity against CAKI1 (IC₅₀ = 1.65 ± 0.24 μM) and A498 (IC₅₀ of 0.85 ± 0.24 μM). Furthermore, the chloroacetyl-containing thiazole compound 7a displayed efficient inhibition of growth against the test cell lines CAKI1 and A498 at low micromolar concentrations, IC₅₀ 0.78 and 0.74 μM, respectively.     

Identification of Alkaloid Compounds Arborinine and Graveoline from Ruta angustifolia (L.) Pers for their Antifungal Potential against Isocitrate lyase (ICL1) gene of Candida albicans

Mycopathologia - Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised...     

Melatonin activates the vascular elements,telocytes, and neuroimmune communication in the adrenal gland of Soay rams during the non-breeding season

Protoplasma - The adrenal glands of 15 adult Soay rams were used to study the effect of melatonin on their vascular elements and cellular organization. A significant increase in the cross-sectional...     

THE EFFECTS OF INJURY PREVENTION WARM-UP PROGRAMMES ON KNEE STRENGTH IN MALE SOCCER PLAYERS

The study investigates the effects of the 11+ and HarmoKnee injury prevention programmes on knee strength in male soccer players. Under-21-year-old players (n=36) were divided equally into: the 11+, HarmoKnee and control groups. The programmes were performed for 24 sessions (20-25 min each). The hamstrings and quadriceps strength were measured bilaterally at 60°·s^-1, 180°·s^-1 and 300°·s^-1. The concentric quadriceps peak torque (PT) of the 11+ increased by 27.7% at 300°·s^-1 in the dominant leg (p<0.05). The concentric quadriceps PT of HarmoKnee increased by 36.6%, 36.2% and 28% in the dominant leg, and by 31.3%, 31.7% and 20.05% at 60°·s^-1, 180°·s^-1 and 300°·s^-1 in the non-dominant leg respectively. In the 11+ group the concentric hamstring PT increased by 22%, 21.4% and 22.1% at 60°·s^-1, 180°·s^-1 and 300°·s^-1, respectively in the dominant leg, and by 22.3%, and 15.7% at 60°·s^-1 and 180°·s^-1, in the non-dominant leg. In the HarmoKnee group the hamstrings in the dominant leg showed an increase in PT by 32.5%, 31.3% and 14.3% at 60°·s^-1, 180°·s^-1 and 300°·s^-1, and in the non-dominant leg hamstrings PT increased by 21.1% and 19.3% at 60°·s^-1 and 180°·s^-1 respectively. The concentric hamstrings strength was significantly different between the 11+ and control groups in the dominant (p=0.01) and non-dominant legs (p=0.02). The HarmoKnee programme enhanced the concentric strength of quadriceps. The 11+ and HarmoKnee programmes are useful warm-up protocols for improving concentric hamstring strength in young professional male soccer players. The 11+ programme is more advantageous for its greater concentric hamstring strength improvement compared to the HarmoKnee programme.     

O-Heterocyclic Embeurekols from Embellisia eureka,an Endophyte of Cladanthus arabicus

Three new polyketides (-)-1 , (+)-1 , and 2 ) were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of (-)-1 , (+)-1 , and 2 were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD analysis, and the modified Mosher method. Chirality 25:250–256, 2013. © 2013 Wiley Periodicals, Inc.     

Interactive effects of excessive potassium and Mg deficiency on safflower

In the present work, separate and combined effects of excessive potassium and magnesium deficiency on safflower (Carthamus tinctorius) were studied. Four treatments were considered: C (control treatment: complete medium containing 1.5 mM Mg), +KCl (excessive potassium treatment: complete medium added with 60 mM KCl), ?Mg (Mg-deficient treatment: containing 0.1 mM Mg), and DS (double stress treatment: Mg-deficient medium (0.1 mM Mg) added with 60 mM KCl. Excessive potassium effect on plant growth was more pronounced than that of Mg deficiency. The two stresses impaired differently plant organs; KCl application affected more roots than shoots, whereas Mg deficiency reduced only leaf biomass. Gas exchange and pigment concentrations and patterns were severely impaired by KCl and mainly by interactive effects of the two stresses. This led to obvious lipid peroxidation and electrolyte leakage. Mg deficiency did not induce lipid peroxidation and electrolyte leakage, but as applied with excessive potassium, it doubled the effect of the latter. Mineral analyses showed that major cation nutrition was disturbed by KCl and combined stresses and at a lower level by magnesium deficiency. Plants did not show an enhanced selectivity of Mg and Ca over K but they improved their use efficiencies.     

Role of evolutionary and ecological factors in the reproductive success and the spatial genetic structure of the temperate gorgonian Paramuricea clavata

Dispersal and mating features strongly influence the evolutionary dynamics and the spatial genetic structure (SGS) of marine populations. For the first time in a marine invertebrate, we examined individual reproductive success, by conducting larval paternity assignments after a natural spawning event, combined with a small‐scale SGS analysis within a population of the gorgonian Paramuricea clavata. Thirty four percent of the larvae were sired by male colonies surrounding the brooding female colonies, revealing that the bulk of the mating was accomplished by males from outside the studied area. Male success increased with male height and decreased with increasing male to female distance. The parentage analyses, with a strong level of self‐recruitment (25%), unveiled the occurrence of a complex family structure at a small spatial scale, consistent with the limited larval dispersal of this species. However, no evidence of small scale SGS was revealed despite this family structure. Furthermore, temporal genetic structure was not observed, which appears to be related to the rather large effective population size. The low level of inbreeding found suggests a pattern of random mating in this species, which disagrees with expectations that limited larval dispersal should lead to biparental inbreeding. Surface brooding and investment in sexual reproduction in P. clavata contribute to multiple paternity (on average 6.4 fathers were assigned per brood), which enhance genetic diversity of the brood. Several factors may have contributed to the lack of biparental inbreeding in our study such as (i) the lack of sperm limitation at a small scale, (ii) multiple paternity, and (iii) the large effective population size. Thus, our results indicate that limited larval dispersal and complex family structure do not necessarily lead to biparental inbreeding and SGS. In the framework of conservation purposes, our results suggested that colony size, proximity among colonies and the population size should be taken into consideration for restoration projects.     

Insulin resistance and early virological response in chronic HCV infection

BackgroundStudies revealed that insulin resistance is associated with fibrosis progression and has negative impact on sustained virological response after standard antiviral therapy in patients with chronic hepatitis C (CHC).AimTo assess the role of IR on progression of liver fibrosis and early virological response (EVR) rates in patients with chronic hepatitis C infection.Patients and methodsThe study population comprised 79 subjects who underwent combination therapy for CHC. Laboratory investigations in the form of glucose, insulin, bilirubin, alanine aminotransferase (ALT), cholesterol and triglycerides and liver biopsy were done for all patients. Insulin resistance was calculated using the homeostasis model of IR (HOMA-IR).ResultsIR was increased (>2 IU) in 31 (40.7%) of patients. Early virological response was achieved among 37 patients (48.7%). No difference in EVR, viral load or grade of liver fibrosis between patients with and without IR. A significant positive correlation was found between IR and liver steatosis.ConclusionInsulin resistance is a common finding in CHC, it is associated with increase liver steatosis. However it has no impact on EVR to combined interferon ribavirin therapy, viral load or necroinflammation.     

Chlamydia trachomatis utilizes the mammalian CLA1 lipid transporter to acquire host phosphatidylcholine essential for growth

Phosphatidylcholine is a constituent of Chlamydia trachomatis membranes that must be acquired from its mammalian host to support bacterial proliferation. The CLA1 (SR‐B1) receptor is a bi‐directional phosphatidylcholine/cholesterol transporter that is recruited to the inclusion of Chlamydia‐infected cells along with ABCA1. C. trachomatis growth was inhibited in a dose‐dependent manner by BLT‐1, a selective inhibitor of CLA1 function. Expression of a BLT‐1‐insensitive CLA1(C384S) mutant ameliorated the effect of the drug on chlamydial growth. CLA1 knockdown using shRNAs corroborated an important role for CLA1 in the growth of C. trachomatis. Trafficking of a fluorescent phosphatidylcholine analogue to Chlamydia was blocked by the inhibition of CLA1 or ABCA1 function, indicating a critical role for these transporters in phosphatidylcholine acquisition by this organism. Our analyses using a dual‐labelled fluorescent phosphatidylcholine analogue and mass spectrometry showed that the phosphatidylcholine associated with isolated Chlamydia was unmodified host phosphatidylcholine. These results indicate that C. trachomatis co‐opts host phospholipid transporters normally used to assemble lipoproteins to acquire host phosphatidylcholine essential for growth.