Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

Socially Defined Subpopulations Reveal Demographic Variation in a Giraffe Metapopulation

Populations are typically defined as spatially contiguous sets of individuals, but large populations of social species can be composed of discrete social communities that often overlap in space. Masai giraffes (Giraffa camelopardalis tippelskirchi) of Tanzania live in distinct social subpopulations that overlap spatially, enabling us to simultaneously explore environmental and social factors correlated with demographic variation in a metapopulation of >1,400 adult females and calves. We considered statistically distinct communities in the social network as subpopulations and tested for variation among the 10 subpopulations in adult female survival, calf survival, and reproductive rate (calf-to-adult female ratio). We then related variation in demographic rates among subpopulations to differences in vegetation, soil type, proximity to 2 types of human settlements, local giraffe population density, and social metrics of relationship strength and exclusivity among adult females. We did not find any among-subpopulation effects on adult female survival, suggesting adult female survival is buffered against environmental heterogeneity among subpopulations. Variation in calf demographic rates among subpopulations were correlated with vegetation, soils, anthropogenic factors, and giraffe population density but not with adult female relationship metrics, despite substantial spatial overlap. Subpopulations with more dense bushlands in their ranges had lower calf survival probabilities, and those closer to human settlements had higher reproductive rates, possibly because of spatial gradients in natural predation. Reproductive rates were higher in subpopulations with more volcanic soils, and calf survival probabilities were greater in subpopulations with higher local adult female densities, possibly related to higher-quality habitat associated with fertile soils or lower predation risk, or to greater competitive ability. The variation in fitness among subpopulations suggests that giraffes do not move unhindered among resource patches to equalize reproductive success, as expected according to an ideal free distribution. The differences in calf survival and reproductive rates could rather indicate intercommunity differences in competitive ability, perception, learning, or experience. Our approach of comparing demography among spatially overlapping yet distinct socially defined subpopulations provides a biologically meaningful way to quantify environmental and social factors influencing fine-scale demographic variation for social species. © 2021 The Wildlife Society.     

Rate of forcing and the forecastability of critical transitions

Critical transitions are qualitative changes of state that occur when a stochastic dynamical system is forced through a critical point. Many critical transitions are preceded by characteristic fluctuations that may serve as model‐independent early warning signals, implying that these events may be predictable in applications ranging from physics to biology. In nonbiological systems, the strength of such early warning signals has been shown partly to be determined by the speed at which the transition occurs. It is currently unknown whether biological systems, which are inherently high dimensional and typically display low signal‐to‐noise ratios, also exhibit this property, which would have important implications for how ecosystems are managed, particularly where the forces exerted on a system are anthropogenic. We examine whether the rate of forcing can alter the strength of early warning signals in (1) a model exhibiting a fold bifurcation where a state shift is driven by the harvesting of individuals, and (2) a model exhibiting a transcritical bifurcation where a state shift is driven by increased grazing pressure. These models predict that the rate of forcing can alter the detectability of early warning signals regardless of the underlying bifurcation the system exhibits, but that this result may be more pronounced in fold bifurcations. These findings have important implications for the management of biological populations, particularly harvested systems such as fisheries, and suggest that knowing the class of bifurcations a system will manifest may help discriminate between true‐positive and false‐positive signals.     

A stereological study of the effects of mercury inhalation on the cerebellum

Mercury in the environment that arises from organic and inorganic sources can cause irreversible damage to the nervous system. Toxicity may be direct or may arise from interactions with other metals in the environment. We evaluated the possible effects of mercury vapor on rat cerebellum. Twelve adult female rats were divided into control and experimental groups. The rats in the experimental group were exposed to mercury vapor for 9 h/day for 45 days. Cerebellar tissue samples were evaluated using stereology and for histopathology. The total number of Purkinje cells was estimated using a physical disector method. We found that in the experimental group, overall volume decreased and the number of Purkinje cells was reduced. We also found cellular damage including pycnotic nuclei, eosinophilic cytoplasm and vacuolization; these features were absent in the control group. We found that chronic exposure to inorganic mercury vapor is toxic to the cerebellum.     

Low‐coverage reduced representation sequencing reveals subtle within‐island genetic structure in Aldabra giant tortoises

Aldabrachelys gigantea (Aldabra giant tortoise) is one of only two giant tortoise species left in the world and survives as a single wild population of over 100,000 individuals on Aldabra Atoll, Seychelles. Despite this large current population size, the species faces an uncertain future because of its extremely restricted distribution range and high vulnerability to the projected consequences of climate change. Captive‐bred A. gigantea are increasingly used in rewilding programs across the region, where they are introduced to replace extinct giant tortoises in an attempt to functionally resurrect degraded island ecosystems. However, there has been little consideration of the current levels of genetic variation and differentiation within and among the islands on Aldabra. As previous microsatellite studies were inconclusive, we combined low‐coverage and double‐digest restriction‐associated DNA (ddRAD) sequencing to analyze samples from 33 tortoises (11 from each main island). Using 5426 variant sites within the tortoise genome, we detected patterns of within‐island population structure, but no differentiation between the islands. These unexpected results highlight the importance of using genome‐wide genetic markers to capture higher‐resolution genetic structure to inform future management plans, even in a seemingly panmictic population. We show that low‐coverage ddRAD sequencing provides an affordable alternative approach to conservation genomic projects of non‐model species with large genomes.     

Healing-promoting effect of bombesin treatment on chronic gastric ulcer in rats

To evaluate whether bombesin treatment has a facilitatory effect on the healing of chronic gastric ulcer, following the induction of ulcer by serosal application of acetic acid, rats were given bombesin (30 microg/kg/day; subcutaneously) or vehicle three times a day for 7, 14 or 21 days until they were decapitated. Neither food intake nor gastric emptying rate in either vehicle-treated or bombesin-treated groups was not statistically different from control rats. Similarly, ulcer indices and gastric myeloperoxidase (MPO) activities at the first and second weeks of injury were not different among the groups. However, in the 3-week ulcer group, bombesin treatment reduced tissue MPO level significantly back to control levels. Moreover, the analysis of the surface epithelium by scanning electron and light microscopy demonstrated a significant reduction in the severity of ulcers by bombesin treatment. Pretreatment with CCK antagonists (L-364,718 or L365,260; 25 micromol/kg/day) before bombesin treatment showed that neither of the CCK antagonists had a significant effect on the bombesin-mediated healing process, suggesting that CCK receptors are not involved in the action of bombesin. In accordance with the previous studies that show its acute gastroprotective effects, bombesin is also effective in promoting the healing process of chronic gastric ulcer in rats.     

Quantification of mesna and total mesna in kidney tissue by high-performance liquid chromatography with electrochemical detection

A sensitive and selective assay for the determination of mesna and total mesna in tissue was developed and validated. After a simple homogenization, extraction and deproteinization step, mesna could be measured immediately by HPLC with an electrochemical detector provided with a sensitive wall-jet gold electrode. Total mesna (i.e., free mesna and mesna present in mesna disulfides and mixed mesna disulfides) could be measured after pre-column reduction with sodium borohydride to free mesna. The lower limit of quantification of mesna and total mesna was for both compounds 10 nmol/g. The assays for mesna and total mesna in tissue were linear over the ranges of 10-3000 and 10-10000 nmol/g, respectively. The within-day and between-day precisions of both methods were better than 9%. The within-day and between-day accuracy of the mesna assay ranged from 103.7 to 113.6%, whereas the accuracies of the total mesna assay ranged from 97.8 to 106.7%. Mesna in an EDTA containing tissue homogenate or in deproteinized tissue homogenate stored at -80 degrees C was stable for at least 12 weeks. Total mesna was stable under all conditions measured. The developed assays will be applied for the determination of the distribution of mesna and total mesna in tissues of the rat after administration of mesna or BNP7787.