Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs

New [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo C-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.     

Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment After Experimental Focal Cerebral Ischemia

The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we aimed to silence VEGF-B expression to assess its contribution to candesartan’s benefit on stroke outcome. Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injections of lentiviral particles containing short hairpin RNA (shRNA) against VEGF-B. Two weeks after lentiviral injections, rats were subjected to either 90 min or 3 h of middle cerebral artery occlusion (MCAO) and randomized to intravenous candesartan (1 mg/kg) or saline at reperfusion. Animals were sacrificed at 24 or 72 h and brains were collected and analyzed for hemoglobin (Hb) excess and infarct size, respectively. Functional outcome at 24, 48 and 72 h was assessed blindly. Candesartan treatment improved neurobehavioral and motor function, and decreased infarct size and Hb. While silencing VEGF-B expression diminished candesartan’s neuroprotective effect, candesartan-mediated vascular protection was maintained even in the absence of VEGF-B suggesting that this growth factor is not the mediator of candesartan’s vascular protective effects. However, VEGF-B is a mediator of neuroprotection achieved by candesartan and represents a potential drug target to improve stroke outcome. Further studies are needed to elucidate the underlying molecular mechanisms of VEGF-B in neuroprotection and recovery after ischemic stroke.     

Recent Acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors.