Evaluating the Effects of Separate and Concomitant Use of MK-2206 and Salinomycin on Prostate Cancer Cell Line

Background:Prostate cancer is known as one of the most prevalent health disorders in the male population globally. The aim of the current study was to evaluate the effects of separate and concomitant use of MK-2206 and salinomycin on prostate cancer cell line.Methods:The antitumor potential of separate and concomitant use of MK-2206 and salinomycin was evaluated in a panel of prostate cancer cell line (PC-3). To get insights into the underlying mechanism of action, different assays including the rate of apoptosis, cell viability, and gene expression were performed in treated prostate cancer cells.Results:A significant reduction was detected in the viability percentage of prostate cancer cells (p< 0.001) and the rate of Akt expression (p< 0.001) in all salinomycin, MK-2206, and salinomycin+MK-2206 groups compared to the negative control group. Furthermore, in comparison with the negative control group, there was a notable increase in both the rate of Bad expression (p< 0.001) and prostate cancer cells apoptosis after salinomycin, MK-2206, and salinomycin+MK-2206 treatments. Moreover, the concomitant use of salinomycin+MK-2206 revealed synergistic improvements regarding the viability of prostate cancer cells and the rate of the Akt and Bad expressions compared to the separate administration of salinomycin and MK-2206 (all p< 0.05)Conclusion:The findings of the present study may contribute to improving the efficacy of the therapies regarding the management of prostate cancer and providing a beneficial strategy in clinical trials.Key Words: Apoptosis, Gene Expression, MK 2206, Prostatic Neoplasms, Salinomycin     

Calprotectin Pegylation Enhanced Its Physical and Structural Properties

Calprotectin is member of the S-100 protein family with a wide plethora of intra-and extracellular functions. Anticancer activities, antimicrobial effects and being a qualified disease marker are among the compelling features of this protein to be used as a pharmaceutical agent. However, there are several impediments to applications of protein pharmaceuticals including: proteolytic degradation, short circulating half-life, low solubility and immunogenicity. Pegylation is a common bioconjugation polymer capable of overcoming these drawbacks. Recombinant expression and purification of calprotectin along with its pegylation would result in enhanced pharmaco-dynamic and pharmacokinetic properties. Our florescence spectroscopy and far Ultraviolet-optical density results indicate that pegylation altered the physical and structural properties of the calprotectin to become in a more stable and functionally active state. Due to enhanced pharmacodynamic and pharmacokinetic properties of the calprotectin via pegylation, this study would pave the way for better in vitro and in vivo validations of calprotectin applications in medical practice.     

Foraminifera and their associations of a possibly Rhaetian section of the Nayband Formation in central Iran,northeast of Esfahan

The following paper describes the foraminiferal fauna and associated faunal assemblages of the bedded and reef carbonates of the Upper Triassic (most probably Rhaetian) Nayband Formation, which are exposed in a section south of the small town of Bagher-Abad, northeast of Esfahan. Foraminifers are extremely rare in sponge- or coral-dominated bioconstructions and in the bedded carbonates of the Nayband Formation in central Iran. Some carbonate beds are composed of bioclastic wackstone/packstone. These are exposed in the solenoporacean horizon at the uppermost part of the section. Here, the aulotortid- and trocholinid-type foraminifers are relatively abundant. The following foraminiferal taxa with different abundances were found within the carbonates of the investigated section: Trocholina umbo Frentzen, T. turris Frentzen, T. gracilis Blau, Aulotortus tumidus (Kristan-Tollmann), Aulotortus tenuis (Kristan), Aulotortus friedli (Kristan-Tollmann), Coronipora etrusca (Pirini), Semiinvoluta clari Kristan, Turrispirillina? licia variabilis Blau, Galeanella? laticarinata Al-Shaibani, Carter and Zaninetti, Ophthalmidium sp., Agathammina sp., “Sigmoilina” schaeferae Zaninetti, Planiinvoluta carinata Leischner, Planiinvoluta sp., Nubecularia sp., Endothyra sp., Paeolituonella sp. and some sessile agglutinated and nodosariid types. All mentioned taxa are very rare, except the involutinid and trocholinid types. The following species are described as new: Trocholina blaui nov. sp., Spirilina? iranica nov. sp., and Coronipora serraforma nov. sp. Trocholina blaui is usually attached to solenoporacean thalli. Four foraminiferal associations, which are named after the occurrence of the abundant species, were distinguished as Aulotortus tumidus association, Aulotortus friedli association, Trocholina umbo association, and Trocholina blaui association. Aulotortid types and Trocholina umbo were found within the bioclastic wackstone/packstone carbonates. Trocholina blaui is abundant in solenoporacean framestones. The foraminiferal association of investigated carbonates contains a mixed fauna, known from Upper Triassic–Liassic in the Tethyan realm. Carbonates of the whole investigated section are dated—due to occurrence of the genus Aulotortus, with species A. tumidus (Kristan-Tollmann), A. tenuis (Kristan), and A. friedli (Kristan-Tollmann)—as Upper Triassic (most probably Rhaetian). The “typical” foraminifers occurring in the reef biotopes in the northwestern Tethys are either missing or extremely rare in the Iranian bioconstructions.     

Dasycladales from the Permian Jamal Formation of the Shotori Mountains,northeast Iran

Calcareous algae of the Permian Jamal Formation were studied in three sections of the Shotori Mountains, located in northeastern Iran. In this paper, four genera including Imperiella Elliott and Süssli, Nanjinoporella Mu and Elliott, Tabasoporella nov. gen., and Pseudotabasoporella nov. gen. are described from the Howz-e Dorah locality, which is exposed about 2 km northeast of the type section of Jamal Formation in Mount Jamal. Tabasoporella nov. gen. is characterized by metaspondyl arrangement of phloiophore and wine-glass-shaped laterals with a stalk grouped to tufts. The individual tufts are separated by a ring-like cavity appearing as triangular, oval, or trapezoid in longitudinally dissected section. The arrangement and shape of the laterals in Pseudotabasoporella nov. gen. is similar to Tabasoporella nov. gen., but there are no cavities between the tufts. All four genera are highly developed and limited to the Permian period. They disappear at the end of Permian and are not found in the Triassic sediments. Until today, two species of Imperiella are found in Iran and Afghanistan. I. iranica Elliott and Süssli was described only from the Ruteh Formation of Alborz Mountains in north Iran and I. afghanica was described from the Permian of Afghanistan. The Jamal Formation of the Shotori Mountains is the second locality where both species are discovered. Moreover, species I. crassiparietalis and I. gracilis are the two new species described here. The genus Nanjinoporella—with type species N. pagoda Mu and Elliott—was known from the Permian (Artinskian) Chishia Formation of Nanjing, China. We describe the new species Nanjinoporella iranica from the Permian Jamal Formation of the Shotori Mountains, northeast Iran.     

Evidence for differential top-down and bottom-up suppression in posterior parietal cortex

When searching for an object, we usually avoid items that are visually different from the target and objects or places that have been searched already. Previous studies have shown that neural activity in the lateral intraparietal area (LIP) can be used to guide this behaviour; responses to task irrelevant stimuli or to stimuli that have been fixated previously in the trial are reduced compared with responses to potential targets. Here, we test the hypothesis that these reduced responses have a different genesis. Two animals were trained on a visual foraging task, in which they had to find a target among a number of physically identical potential targets (T) and task irrelevant distractors. We recorded neural activity and local field potentials (LFPs) in LIP while the animals performed the task. We found that LFP power was similar for potential targets and distractors but was greater in the alpha and low beta bands when a previously fixated T was in the response field. We interpret these data to suggest that the reduced single-unit response to distractors is a bottom-up feed-forward result of processing in earlier areas and the reduced response to previously fixated Ts is a result of active top-down suppression.     

Wnt signalling pathway and tau phosphorylation: A comprehensive study on known connections

The Wnt pathway is the most important cascade in the nervous system; evidence has indicated that deregulation of the Wnt pathway induced pathogenic hallmarks of neurodegenerative diseases. Glycogen synthase kinase-3β (GSK-3β) as the main member of the Wnt pathway increases tau inclusions, the main marker in the neurodegenerative diseases. Phosphorylated tau is observed in the pre-tangle of the neurons in the early stage of neurodegenerative diseases. The researchers always try to improve pharmacological approaches of new therapeutic strategies to the treatment of neurodegenerative diseases that are required to represent a significant entry point by understanding the theoretical interactions of the molecular pathways. In this review, we have discussed the recent knowledge about the canonical and non-canonical Wnt signalling pathway, GSK-3β, Wnt/β-catenin antagonists, tau phosphorylation, and their important roles in the neurodegenerative diseases.     

Sponges from the Permian of Hambast Mountains,south of Abadeh,central Iran

Upper Permian (Murghabian) sponges from the Surmaq Formation exposed in the Hambast Mountains, south of Abadeh, central Iran are described. The sponge fauna of the Surmaq Formation is composed of at least 26 taxa, including 12 species of sphinctozoans, 12 species of inozoans, one operculospongid, and one lithistid species. The following taxa were determined to genus or species level: Sphinctozoa: Family Sebargasiidae: Amblysiphonella hambastensis n. sp., Discosiphonella iranica n. sp., Family Colospongiidae: Colospongia cortexifera Senowbari-Daryan and Rigby, Exaulipora permica (Senowbari-Daryan), Platythalamiella sp. 1, Platythalamiella? sp. 2, Parauvanella minima Senowbari-Daryan, Colospongia? or Neoguadalupia? sp., Family Guadalupiidae: Cystothalamia surmaqensis n. sp., Imbricatocoelia cf. paucipora Rigby, Fan and Zhang, Family Thaumastocoeliidae: Sollasia ostiolata Steinmann, Family Cryptocoeliidae: Stylocoelia circopora Wu. Inozoa: Family Peronidellidae: Preperonidella cf. Preperonidella recta grossa (Wu), Heptatubispongia symmetrica Rigby and Senowbari-Daryan, Hambastella sincassa n. gen., n. sp., Hambastella cumcassa n. sp., Family Maeandrostiidae: Maeandrostia kansasensis Girty, Maeandrostia? dubia n. sp., Surmaqella pustulata n. gen., n. sp., Family Auriculospongiidae: Pseudopalaeoaplysina huayingensis Wang, Qiang and Zhang, Family Disjectoporidae: Disjectopora beipeiensis Fan, Rigby and Zhang, Lichuanopora cf. bancaoensis Fan, Rigby and Zhang, Family Khmeriidae: Imilce newelli Flügel. Lithistida: Family Astylospongiidae: Raanespongia iranica n. sp. Among the sphinctozoans A. hambastensis n. sp. is an extremely abundant species. Among the inozoans the genus Hambastella n. gen., with both species, is the most abundant genus. The genera Disjectopora, Lichuanopora, and Pseudopaleoaplysina, were described as hydrozoans by early workers, but are assigned to the inozoans in this paper. The Upper Permian sponge fauna, as well as the composition of other reef organisms, from the Hambast Mountains in central Iran is different from that of the assemblage in the Lower Permian reefal limestones of Bagh-e Vang from the Shotori Mountians (northeast Iran).     

Middle Permian calcareous algae and microproblematica (Dalan Formation, Dena Mountain, High Zagros, SW Iran)

Calcareous algae and microproblematica have been studied in the Middle Permian part of the Dalan Formation in Dena Mountain, Zagros, southwest Iran. Murgabian (=Wordian) microfossils are the most diversified. The assemblages encompass, among the dasycladales, Anthracoporella spectabilis, Epimastopora piae, Epimastoporella japonica, E. likana, Paraepimastopora? cf. densipora n. comb., Gyroporella cf. nipponica, G.? aff. fluegeli n. comb., G.? aff. symmetrica, G.? aff. digitula n. comb., Mizzia yabei; among the gymnocodiaceans, Gymnocodium bellerophontis, G. nodosum, Permocalculus cf. digitatus, P. forcepinus, P. cf. fragilis, P. plumosus, P. cf. solidus, Tauridium? sp.; among the “phylloid algae” Eugonophyllum? sp.; among the other incertae sedis algae Stacheoides sp., Ungdarella uralica, Fourstonella (Efluegelia) johnsoni, and among some microproblematica alternatively assigned to foraminifers or algae Aeolisaccus dunningtoni, Tubiphytes obscurus, Pseudovermiporella nipponica, P. sodalica, and P. longipora. Each taxon is briefly characterized, whereas a more detailed analysis of the epimastoporacean algae is given. Among them, the genera Epimastopora and Epimastoporella are emended. All the described microfossils have a relatively broad stratigraphic distribution in the Permian period but they are paleoecologically important. They are indeed confident micropaleontological Middle Permian proxies, particularly for shallow-marine, warm, well-oxygenated and relatively high-energy environments. They were affected by the end-Guadalupian crisis because they strongly decrease in the upper carbonate unit of the Dalan Formation and are not found in the Triassic sediments of the area.