Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation

Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro.     

Bacillus thuringiensis beyond insect biocontrol: plant growth promotion and biosafety of polyvalent strains

The entomopathogenic bacteriumBacillus thuringiensis is widely used for the control of many agricultural insect pests and vectors of human diseases. Several studies reported also on its antibacterial and antifungal activities. However, to our knowledge there were no studies dealing with its capacity to act as a plant growth promoting bacterium. This review surveys the potential ofB. thuringiensis as a polyvalent biocontrol agent, a biostimulator and biofertiliser bacterium that could promote the plant growth. Also, discussed is the safety ofB. thuringiensis as a bacterium phylogenetically related toBacillus cereus the opportunistic human pathogen andBacillus anthracis, the etiological agent of anthrax.     

Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway

Cervical cancer (CCa) is the second most frequent carcinoma in females and human papilloma virus (HPV) oncoproteins are regarded as one of the critical etiological agent. Despite recent advances in screening and management of CCa, still it remains the deadliest carcinoma as advanced and metastatic stages are mostly incurable. This urges for the development of newer therapeutic interventions. The current was aimed to investigate the antiproliferative and apoptotic potential of glycyrrhizin (Gly) against HPV16⁺ CaSki CCa cells. Our findings substantiated that Gly exerted antiproliferative effects on the CaSki cells by obstructing their proliferation rate. Gly substantially enhanced apoptosis in Caski cells in a dose-dependent manner via augmenting the generation of ROS, DNA fragmentation and disruption of the mitochondrial membrane potential. Gly mediated apoptosis in CaSki cells was found to be due to activation of caspase-8 and capsase-9 along with the modulation of pro-and anti-apoptotic gene expression. Moreover, Gly halts the progression of CaSki cells at G₀/G₁ phase which was found to be due to reduced expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) along with the enhanced expression of CDK inhibitor p21^Cip1. Further, Gly downregulates the expression of HPV oncoproteins (E6 & E7) along with the inhibition of Notch signaling pathway. Taken together, Gly represents as a potential therapeutic modality for CCa which could rapidly be translated for clinical studies.     

Tea prepared from Anastatica hirerochuntica seeds contains a diversity of antioxidant flavonoids, chlorogenic acids and phenolic compounds

HPLC-PDA-MS(2) was used to identify phenolic and polyphenolic compounds in an herbal tea made from seeds of Anastatica hirerochuntica, a plant found in the Sahara-Arabian deserts and used to treat a variety of ailments. Twenty compounds comprising a series of flavone C- and O-linked glycosides, phenolic acids, chlorogenic acids and flavonols were identified or partially identified on the basis of co-chromatography with reference compounds and MS(2) and MS(3) fragmentation patterns. The flavones were the principal components, occurring as luteolin, apigenin and diosmetin conjugates. The antioxidant potential of individual compounds in Anastatica was assessed using HPLC with an on-line ABTS·(+) detection system. This revealed that 14 compounds exhibited antioxidant activity. The highest contribution to the antioxidant capacity of the tea, 56%, came from 3,4-dihydroxybenzoic acid and caffeoyl- and dicaffeoylquinic acids while 6-C-glucosides of luteolin and apigenin contributed 41%.     

Stereological and histopathological assessment of intrauterine growth restriction placenta from Saudi women

BackgroundPlacental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR.MethodsOverall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques.ResultsThe IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group.ConclusionThe reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention.     

Diversity of Bacillus anthracis strains in Georgia and of vaccine strains from the former Soviet Union

Despite the increased number of anthrax outbreaks in Georgia and the other Caucasian republics of the former Soviet Union, no data are available on the diversity of the Bacillus anthracis strains involved. There is also little data available on strains from the former Soviet Union, including the strains previously used for vaccine preparation. In this study we used eight-locus variable-number tandem repeat analyses to genotype 18 strains isolated from infected animals and humans at different sites across Georgia, where anthrax outbreaks have occurred in the last 10 years, and 5 strains widely used for preparation of human and veterinary vaccines in the former Soviet Union. Three different genotypes affiliated with the A3.a cluster were detected for the Georgian isolates. Two genotypes were previously shown to include Turkish isolates, indicating that there is a regional strain pattern in the South Caucasian-Turkish region. Four of the vaccine strains were polymorphic, exhibiting three different patterns of the cluster A1.a genotype and the cluster A3.b genotype. The genotype of vaccine strain 71/12, which is considered an attenuated strain in spite of the presence of both of the virulence pXO plasmids, appeared to be a novel genotype in the A1.a cluster.     

Identification of a new developmentally regulated Leishmania major large RAB GTPase

Here, we describe for the first time a Leishmania specific gene encoding a large 610 amino-acid RAB GTPase (LmLRAB). LmLRAB displays high homologies with the RAB GTPase protein family between amino acids 34 and 284. It contains characteristic signatures of RAB proteins: 4 GTP binding domains, 5 RAB specific domains, 3 RAB subfamily-specific domains, and a prenylation site. lmlrab is a single copy gene, transcribed as a 3.5 kb mRNA, highly conserved in Leishmania species, and encodes a protein doublet of approximately 75 kDa. Immunofluorescence microscopy using LmLRAB-specific antibodies demonstrated that LmLRAB is confined in a structure adjacent to the kinetoplast probably corresponding to an early endosomal/golgi apparatus localization. Interestingly, using quantitative real-time RT-PCR, we showed that the lmlrab gene is up-regulated twice in amastigotes relative to promastigotes. These findings suggest that LmLRAB may play a potential role in Leishmania pathogenicity.     

Identification of One Novel Candidate Probiotic Lactobacillus plantarum Strain Active against Influenza Virus Infection in Mice by a Large-Scale Screening

In this study, we developed a large-scale screening of bacterial strains in order to identify novel candidate probiotics with immunomodulatory properties. For this, 158 strains, including a majority of lactic acid bacteria (LAB), were screened by two different cellular models: tumor necrosis factor alpha (TNF-α)-activated HT-29 cells and peripheral blood mononuclear cells (PBMCs). Different strains responsive to both models (pro- and anti-inflammatory strains) were selected, and their protective effects were tested in vivo in a murine model of influenza virus infection. Daily intragastric administrations during 10 days before and 10 days after viral challenge (100 PFU of influenza virus H1N1 strain A Puerto Rico/8/1934 [A/PR8/34]/mouse) of Lactobacillus plantarum CNRZ1997, one potentially proinflammatory probiotic strain, led to a significant improvement in mouse health by reducing weight loss, alleviating clinical symptoms, and inhibiting significantly virus proliferation in lungs. In conclusion, in this study, we have combined two cellular models to allow the screening of a large number of LAB for their immunomodulatory properties. Moreover, we identified a novel candidate probiotic strain, L. plantarum CNRZ1997, active against influenza virus infection in mice.