Protective effect of pilin protein with alum+naloxone adjuvant against acute pulmonary Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa is an important opportunistic human pathogen that causes a wide variety of severe nosocomial infections. Type IV pili of P. aeruginosa are made up of polymerized pilin that aids in bacterial adhesion, biofilm formation and twitching motility. The aim of this study was to evaluate the efficacy of alum and naloxone (alum+NLX) as an adjuvant for P. aeruginosa recombinant PilA (r-PilA) as a vaccine candidate in the improvement of humoral and cellular immunity. Primary immunization with r-PilA in combination with alum+NLX followed by two booster shots was sufficient to generate robust cellular and humoral responses, which were Th1 and Th2 type responses consisting of IgG1 and IgG2a subtypes. Analysis of the cytokine response among immunized mice showed an increased production of IL-4, INF-γ and IL-17 by splenocytes upon stimulation by r-PilA. These sera were also able to reduce bacterial load in the lung tissue of challenged mice. The reduction of systemic bacterial spread resulted in increased survival rates in challenged immunized mice. In conclusion, immunization with r-PilA combined with alum+NLX evokes cellular and humoral immune responses, which play an important role in providing protection against acute P. aeruginosa lung infection among immunized mice.

Novel Tacrine-Based Pyrano[3',4':5,6]pyrano[2,3-b]quinolinones: Synthesis and Cholinesterase Inhibitory Activity.

In order to develop effective anti-cholinesterase compounds, a novel series of pyrano[3',4':5,6]pyrano[2,3-b]quinolinones were designed, synthesized, and evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All derivatives showed very good AChE inhibitory (AChEI) activity (IC50 = 0.37-5.62 µM) compared with rivastigmine (IC50 = 11.07 µM). Among them, 11-amino-12-(2,3-dichlorophenyl)-3-methyl-7,8,9,10-tetrahydropyrano[3',4':5,6]pyrano[2,3-b]quinolin-1(12H)-one (6f) displayed the best inhibitory activity. However, most of the synthesized compounds showed no anti-BChE activity and compounds 6b and 6f were found to be only moderate inhibitors. The most potent anti-AChE compound 6f had low and moderate inhibitory activity and neuroprotective effects against beta-secretase (BACE1) and oxidative stress-induced cell death, respectively. Also, kinetic and molecular docking studies of binding interactions elucidated that compound 6f bound to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

Interpersonal violence among the Chalcolithic and Bronze Ages inhabitants living on the Central Plateau of Iran: A voice from Tepe Hissar.

ABSTRACT: The site of Tepe Hissar (Iran) experienced widespread cultural and economic changes during the Chalcolithic and Bronze Ages (5th to the 2nd millennium B.C.). The discovery of evidence of burning, including charred human remains, the destruction of buildings (Periods II and III), and the presence of several mass-burials with comingling of human skeletal remains consisting of ten or more individuals (Period III), suggests interpersonal violence during these periods. The original excavator of Tepe Hissar, Erich Schmidt, suggested that phenomena such as war, massacres, epidemics, or similar catastrophes, may have been responsible for the excavated archaeological evidence. This study tests the hypothesis that interpersonal violence was responsible for this evidence. Patterns of violence related head injury are explored among 129 adult men and women from the Chalcolithic and Bronze Ages. Sixty of the 129 (46.5%) crania examined presented with cranial trauma, with 25 (19.3%) having evidence of perimortem injury, and four (3.1%) and 31 (24%) individuals with signs of healing and healed head/facial trauma, respectively. Most of the injuries were located on the frontal or parietal bones of the cranium. Such findings may be interpreted as a result of the population experiencing a rise in social complexity and population increase that accompanied violence related to intra- or inter-group competition, often leading to lethal outcomes. These data support the hypothesis that the cultural and economic transitions and population changes that occurred at Tepe Hissar, and particularly in the Hissar II and III periods, were accompanied by tension and interpersonal violence.