Antioxidant-rich date palm fruit extract inhibits oxidative stress and nephrotoxicity induced by dimethoate in rat

Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well-known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p < 0.01) in addition to a significant decrease in serum uric acid (p < 0.05). Interestingly, these drastic modifications were accompanied by a marked enhancement of lipid peroxidation in kidney, indicating a significant induction of oxidative damage (p < 0.01) and dysfunctions of enzymatic antioxidant defenses. These biochemical alterations were also accompanied by histological changes in kidney revealed by a narrowed Bowman’s space, tubular degeneration, tubular cell desquamation, and tubular dilatation of proximal tubules. Treatment with date palm fruit extract (Deglet Nour) and also with vitamin C significantly (p < 0.05) reversed the serum renal markers to their near-normal levels when compared with dimethoate-treated rats. In addition, Deglet Nour extract and vitamin C significantly reduced lipid peroxidation, restored the antioxidant defense enzymes in the kidney, and improved the histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress-induced nephrotoxicity.     

Erratum to: C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients

Neurochemical Research -     

Identification of Molecular Markers Associated with Alteration of Receptor-Binding Specificity in a Novel Genotype of Highly Pathogenic Avian Influenza A(H5N1) Viruses Detected in Cambodia in 2013

Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.     

Let-7f microRNA negatively regulates hepatic differentiation of human adipose tissue-derived stem cells

MicroRNAs (miRNAs) are noncoding RNAs involved in the regulation of the diverse biological processes such as metabolism, proliferation, and cell cycle, in addition to regulation of differentiation. So far, some miRNAs have been recognized to have important role in regulating hepatic functions. Statistically, let-7f has been revealed as a negative regulator of hepatic differentiation. In the present study, we investigated the effect of let-7f on hepatic differentiation of human adipose tissue-derived stem cells (hADSCs). hADSCs were transduced with recombinant lentivirus containing human inhibitor let-7 f. The expression of hepatocyte nuclear factors alpha (HNF4a), albumin (ALB), alpha fetoprotein (AFP), cytokeratin 18 (CK18), and cytokeratin 19 (CK19) was evaluated using quantitative real-time PCR (qRT-PCR). Immunocytochemistry was used to investigate the expression levels of the hepatocyte markers including ALB, AFP, and HNF4a, and biochemical analysis was implemented for hepatic function, glycogen deposition, and urea secretion. qRT-PCR showed significant upregulation in HNF4a, ALB, AFP, CK18, and CK19 expression in cells transduced with let-7f inhibitor lentiviruses. Moreover, positive staining was detected for ALB, AFP, and HNF4a using immunocytochemistry. Urea production and glycogen deposits were also found in the treated cells, the two specific features of the hepatic cells. Therefore, let-7f silencing led to the increased expression of the hepatocyte-specific factors and the accelerated hADSCs hepatic differentiation. Summing all these finding together, our present report has provided evidences that inhibition of let-7f would facilitate induction of hADSCs into hepatocyte-like cells and possibly in regenerative therapy of the liver disease in a wider spectrum.     

High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor

Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3′,5′-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 10⁵ GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces “molecule noise.” Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons.     

A Method to Evaluate the Effect of Contact with Excipients on the Surface Crystallization of Amorphous Drugs

Amorphous drugs are used to improve the solubility, dissolution, and bioavailability of drugs. However, these metastable forms of drugs can transform into more stable, less soluble, crystalline counterparts. This study reports a method for evaluating the effect of commonly used excipients on the surface crystallization of amorphous drugs and its application to two model amorphous compounds, nifedipine and indomethacin. In this method, amorphous samples of the drugs were covered by excipients and stored in controlled environments. An inverted light microscope was used to measure in real time the rates of surface crystal nucleation and growth. For nifedipine, vacuum-dried microcrystalline cellulose and lactose monohydrate increased the nucleation rate of the β polymorph from two to five times when samples were stored in a desiccator, while d-mannitol and magnesium stearate increased the nucleation rate 50 times. At 50% relative humidity, the nucleation rates were further increased, suggesting that moisture played an important role in the crystallization caused by the excipients. The effect of excipients on the crystal growth rate was not significant, suggesting that contact with excipients influences the physical stability of amorphous nifedipine mainly through the effect on crystal nucleation. This effect seems to be drug specific because for two polymorphs of indomethacin, no significant change in the nucleation rate was observed under the excipients.KEY WORDS: amorphous, drugs, growth rate, nucleation rate, tablet excipients     

Post‐last glacial maximum expansion from Iberia to North Africa revealed by fine characterization of mtDNA H haplogroup in Tunisia

The first large‐scale fine characterization of Tunisian H lineages clarifies that the post‐Last glacial maximum expansion originating in Iberia not only led to the resettlement of Europe but also of North Africa. We found that 46% of 81 Tunisian H lineages subscreened for 1,580 bp in mtDNA coding region were affiliated with H1 and H3 subhaplogroups, which are known to have originated in Iberia. Although no signs of local expansion were detected, which would allow a clear dating of their introduction, the younger and less diverse Tunisian H1 and H3 lineages indicate Iberia as the radiating centre. Major contributions from historical migrations to this Iberian genetic imprint in Tunisia were ruled out by the mtDNA gene pool similarity between Berber/Arab/cosmopolitan samples and some “Andalusian” communities, settled by the descendents of the “Moors” who once lived in Iberia for 10 centuries (between 8th and 17th centuries), before being expelled to Tunisia. Am J Phys Anthropol, 2009. © 2008 Wiley‐Liss, Inc.     

Ancient local evolution of African mtDNA haplogroups in Tunisian Berber populations

Our objective is to highlight the age of sub-Saharan gene flows in North Africa and particularly in Tunisia. Therefore we analyzed in a broad phylogeographic context sub-Saharan mtDNA haplogroups of Tunisian Berber populations considered representative of ancient settlement. More than 2,000 sequences were collected from the literature, and networks were constructed. The results show that the most ancient haplogroup is L3*, which would have been introduced to North Africa from eastern sub-Saharan populations around 20,000 years ago. Our results also point to a less ancient western sub-Saharan gene flow to Tunisia, including haplogroups L2a and L3b. This conclusion points to an ancient African gene flow to Tunisia before 20,000 BP. These findings parallel the more recent findings of both archaeology and linguistics on the prehistory of Africa. The present work suggests that sub-Saharan contributions to North Africa have experienced several complex population processes after the occupation of the region by anatomically modern humans. Our results reveal that Berber speakers have a foundational biogeographic root in Africa and that deep African lineages have continued to evolve in supra-Saharan Africa.     

Elevated expression of human alpha-1 antitrypsin mediated by yeast intron in Pichia pastoris

Intron-mediated enhancement has been documented in many cases to involve large positive effect on gene expression. To address this, human Alpha-1 antitrypsin (hAAT) gene was integrated into Pichia pastoris with and without a yeast intron generated from the final plasmid pBlu-exII-int-exIII and ligated into the EcoRI/BamHI multiple cloning site of the yeast shuttle vector pHIL-S1. The chimeric exon–intron complex in the middle of the naturally occurring hAAT exons II and III caused a 23-fold enhancement of hAAT expression in P. pastoris, measured through SDS-PAGE and immunoblot analyses.     

3-Hydrogenkwadaphnin induces monocytic differentiation and enhances retinoic acid-mediated granulocytic differentiation in NB4 cell line

Recently, we have reported that 3-hydrogenkwadaphnin (3-HK), a diterpene ester isolated from Dendrostellera lessertii (Thymealeaceae), is very effective against leukemia cell lines without any detectable effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK induces G1 cell-cycle arrest, differentiation and apoptosis in APL NB4 cell line. Indeed, the drug between 24 to 96 h induced 7-65% growth inhibition of NB4 cells. Cell viability was also decreased by 2-55% between 24 to 96 h treatments with the drug, respectively. These effects of the drug were also dose-dependent. According to flow cytomtry results, 3-HK (15 nM) induced a significant G1-arrest up to 24 h which was consequently followed with appearance of sub-G(1) peak at 72 to 96 h. Hoechst 33258 staining and DNA fragmentation assays confirmed the occurrence of apoptosis among the treated cells. On the other hand, NBT reducing assay, Wright-Giemsa staining, phagocytic activity and expression of cell surface markers (CD11b and CD14) confirmed that the inhibition of proliferation is associated with differentiation especially toward macrophage-like morphology. Interestingly, 3-HK at 5 and 10 nM enhanced the effects of all-trans retinoic acid (ATRA) in NB4 cells. Based on these results, 3-HK might become an ideal candidate for treatment of APL patients pending full exploration of its biological functions.