Novel (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives: Selective inhibition of MV-4-11 biphenotypic B myelomonocytic leukemia cells’ growth is accompanied by reactive oxygen species overproduction and apoptosis

A series of optically pure (R)- and (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives was designed and synthesized as novel anthramycin analogues in a three-step, one-pot procedure, and tested for their antiproliferative activity on nine following cell lines: MV-4-11, UMUC-3, MDA-MB-231, MCF7, LoVo, HT-29, A-549, A2780 and BALB/3T3. The key structural features responsible for exhibition of cytotoxic effect were determined: the (S)-configuration of chiral center and the presence of hydrophobic 4-biphenyl substituent in the side chain. Introduction of bromine atom into the 8 position (8g) or substitution of dilactam ring with benzyl group (8m) further improved the activity and selectivity of investigated compounds. Among others, compound 8g exhibited selective cytotoxic effect against MV-4-11 (IC₅₀?=?8.7?μM) and HT-29 (IC₅₀?=?17.8?μM) cell lines, while 8m showed noticeable anticancer activity against MV-4-11 (IC₅₀?=?10.8?μM) and LoVo (IC₅₀?=?11.0?μM) cell lines. The cell cycle arrest in G₁/S checkpoint and apoptosis associated with overproduction of reactive oxygen species was also observed for 8e and 8m.     

Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and in Newborn Cord Blood Postpartum—Preliminary Study

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 μg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 μg/ml; p < 0.0001, Fe: 1.96 ± 0.43 μg/ml; p < 0.0001, Zn: 0.65 ± 0.16 μg/ml; p < 0.0001, Cu: 0.36 ± 0.09 μg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 μg/ml; p < 0.0001, Fe: 1.63 ± 0.30 μg/ml; p < 0.0001, Zn: 0.65 ± 0.15 μg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 μg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 μg/ml, Fe: 0.82 ± 0.35 μg/ml, Zn: 0.46 ± 0.16 μg/ml, and Cu: 1.90 ± 0.35 μg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = ?0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = ?0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women’s blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.     

Investigating Niche Construction in Dynamic Human-Animal Landscapes: Bridging Ecological and Evolutionary Timescales

Human influence on the environment is evident at all landscape and ecological scales, from local to global, shaping both abiotic and biotic processes. Niche construction theory provides a means by which to investigate the consequences of these anthropogenic effects, but primatological research has been slow to integrate ecological and evolutionary timelines. We review methods that can be used to study how human niche construction influences nonhuman primates including phenological assessment, nonhuman primate behavioral observations, and ethnographic interview techniques. We argue that this approach provides a starting place to examine niche construction theory but that scholars of primate behavioral ecology must expand our methodologies to bridge the disconnect between ecological and evolutionary research time frames. We suggest areas of research and methods that have been underused but offer opportunities for integrative, innovative research. We conclude that an integrated, synthetic methodological approach is a major goal and that it will likely require a cross-disciplinary, collaborative effort.     

Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives

Syzygium is a large genus of flowering plants, with several species, including the clove tree, used as important resources in the food and pharmaceutical industries. In our continuing search for anticancer agents from higher plants, a chloroform extract of the leaves and twigs of Syzygium corticosum collected in Vietnam was found to be active toward the HT-29 human colon cancer cell line. Separation of this extract guided by HT-29 cells and nuclear factor-kappa B (NF-κB) inhibition yielded 19 known natural products, including seven triterpenoids, three ellagic acid derivatives, two methylated flavonoids, a cyclohexanone, four megastigmanes, a small lactone, and an aromatic aldehyde. The full stereochemistry of (+)-fouquierol (2) was defined for the first time. Biological investigations showed that (+)-ursolic acid (1) is the major cytotoxic component of S. corticosum, which exhibited also potent activities in the NF-κB and mitochondrial transmembrane potential (MTP) inhibition assays conducted, with IC₅₀ values of 31?nM and 3.5?µM, respectively. Several analogues of (+)-ursolic acid (1) were synthesized, and a preliminary structure-activity relationship (SAR) study indicated that the C-3 hydroxy and C-28 carboxylic acid groups and 19,20-dimethyl substitution are all essential in the mediation of the bioactivities observed for this triterpenoid.     

Antibacterial and immunomodulatory activities of bovine lactoferrin against <Emphasis Type="Italic">Escherichia coli</Emphasis> O157:H7 infections in cattle

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a zoonotic pathogen that causes food-borne disease in humans ranging from watery diarrhea to bloody diarrhea and severe hemorrhagic colitis, renal failure and hemolytic uremic syndrome. Cattle, the most important source of E. coli O157:H7 transmission to humans, harbor the bacteria in their gastrointestinal tract without showing clinical symptoms. Prevention of E. coli O157:H7 infections in ruminants could diminish the public health risk. However, there is no specific treatment available nor a vaccine or a therapeutic agent which completely prevents E. coli O157:H7 infections in cattle. This paper provides an overview of latest research data on eradicating enterohemorrhagic E. coli O157:H7 in ruminants by use of bovine lactoferrin administration. The article provides insights into the anti-microbial and immunomodulatory activities of bovine lactoferrin against E. coli O157:H7 infections in cattle.     

Range extension of a boreal amphipod Gammarus oceanicus in the warming Arctic

The recent (2008–2016) occurrence of a boreal intertidal amphipod Gammarus oceanicus along the Spitsbergen coast is compared with corresponding data from 1980 to 1994. We aimed to compare the pace of environmental changes in the area (ice retreat, temperature increase) with distribution change of G. oceanicus. Material for the study was collected from intertidal, at low water level from over 100 locations on Spitsbergen, the main island of Svalbard archipelago (expanding from 76 to 80°N). The west coast of the island has been exposed to a steady increase in sea surface and air temperature (2°C in 20 years), as well as a significant decrease in fast ice duration (from over 5 months to less than 1 per year). A total length of more than 3,600 km of the island's coastline has been recently impacted by warming. Of the two sibling Gammarus species that dwell in the Spitsbergen littoral, G. setosus, the local cold water species remains generally where it was observed about 20–30 years ago. By contrast, boreal G. oceanicus has expanded its distribution range by over 1,300 km along the west and north coasts of Spitsbergen and gained dominating position on the number of sites, where it was previously just an occasional species.     

Evaluation of anti-human antibodies for immunohistochemistry on archival nonhuman primate tissues

Abstract: A panel of commercially available antibodies which recognize specific antigens on human tissues was developed for use in immunohistochemistry on tissues from eight species of nonhuman primates. Antibodies were selected for potential usefulness in diagnostic pathology, and for effectiveness in formalin-fixed, paraffin-embedded tissues. Tissues from four species of macaques and four New World monkeys were evaluated. Using these antibodies we were able to identify 17/21 antigens examined in all eight species, and 21/21 antigens in the four species of macaques. Detailed immunohistochemistry protocols are presented, along with a systematic approach to developing a protocol for a new antibody.