Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination

Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose- and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array^® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated ≥3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers.     

Hybrid coating of alginate microbeads based on protein-biopolymer multilayers for encapsulation of probiotics

A hybrid coating based on multilayers of proteins and biopolymers was developed to enhance the protection performance of alginate microbeads against acidic conditions for delivery of probiotics (Lactobacillus rhamnosus GG). Zeta potential measurements and quartz crystal microbalance with dissipation confirmed layer-by-layer deposition of protein-polymer layers. The stability of protein-based coatings during simulated gastric fluid (SGF) treatment was monitored by microscopy. Protein-coated microbeads were partially dismantled, whereas polymer-coated microbeads were intact after a sequential treatment in simulated gastric and intestinal fluids. This suggests that hybrid formulation offers an advantage over the coatings based on biopolymer multilayers in terms of better release of bacteria. Uncoated alginate microbeads completely dissolved and could not protect bacteria after SGF treatment whereas microbeads with hybrid coating showed increased physical stability and a modest decrease of culturability of 3.8 log units. Therefore, this work provides a concept for future protein-based hybrid coatings for bacterial delivery systems.     

Circulating nuclear factor-kappa B mediates cancer-associated inflammation in human breast and colon cancer

BackgroundInflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-κB) levels as a circulating marker in the monitoring of inflammation in breast and colon cancer; to show the relationship between NF-κB with inflammatory parameters as tumour necrosis factor-α (TNF-α), soluble TNF-related apoptosis-inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels.MethodsSerum NF-κB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls.ResultsThe serum NF-κB, TNF-α, IL-6, PTX-3, PCT, and serum CRP concentration was significantly higher, and the serum sTRAIL concentration was significantly lower in the patients with breast and colon cancer than in healthy controls. NF-κB was positively correlated with CRP and negatively correlated with sTRAIL.ConclusionsThese results suggest that increased NF-κB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is a relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute-phase proteins, or by abnormalities in circulating cells. NF-κB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumour, and conventional radio and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.     

Changes in functional composition and diversity of waterbirds: The roles of water level and submerged macrophytes

1. Water level and submerged macrophytes are critical players for the functioning of shallow lake ecosystems; understanding how waterbird communities respond to changes in both can have important implications for conservation and management. Here, we evaluated the effects of changes in water level and submerged macrophyte status on wintering waterbird community size, functional group abundances, functional diversity (FD), and community assembly by using a dataset compiled over 50 years.
2. We built generalised linear models to evaluate the effects of water level and submerged macrophyte status on the above-listed attributes of the waterbird communities by using mid-winter waterbird censuses, water level measurements, and submerged macrophyte surveys, along with submerged macrophyte macrofossil records from two shallow lakes in Turkey. Using a relevant set of functional traits, we defined functional groups, calculated four FD measures, and simulated null distributions of the FD measures for assessing assembly rules.
3. We found that macrophyte-dominated years had significantly higher abundances of waterbirds in one of the study lakes, and had more diving herbivores and omnivores in both lakes, while diving/scooping fish-eating waterbird abundance was lower in macrophyte-dominated years. Community size in Lake Beyşehir exhibited a negative association with water level; surprisingly, however, none of the functional group abundances and FD indices were significantly related to water level.
4. In our study communities, standardised effect sizes of functional richness and functional dispersion—two indices that are particularly sensitive to community assembly processes—were mostly lower than those of randomly assembled communities, which implies functional clustering. Shifts to a scarce-macrophyte state were associated with increases in these two indices, possibly due to either changes in the relative strength of environmental filtering and limiting similarity in community assembly or sampling of transitional communities. Further studies covering a wider range of the trophic/macrophyte status spectrum are needed to be certain.
5. The results of this study indicate that shifts between abundant and scarce-macrophyte states can have significant effects on wintering waterbird abundances, FD and community assembly. The results also suggest that shallow lakes in macrophyte-dominated states can support more wintering waterbirds, especially diving omnivores, some of which are globally threatened.

     

Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome?

BackgroundThis study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS).Methods80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined.ResultsThe average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to below. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality.ConclusionsWe can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.     

Contamination and environmental risk assessment of heavy metals in marine sediments from Tahaddart estuary (NW of Morocco)

Abstract

The distribution, contamination status, and ecological risks of heavy metals in Tahaddart estuary were investigated. 24 surface sediment samples and two cores were collected and analyzed for major (Al and Fe), heavy metals (As, Cd, Cr, Cu, Ni, Pb, and Zn), and grain size composition. The heavy metals assessment was carried out using different environmental indices. The results indicated that the spatial distribution patterns of Al, Fe, and Zn were mainly determined by the distribution of the finer grained fraction (<63?μm) in the sediment. In contrast, As, Cd, Cr, Cu, Ni, and Pb concentrations were controlled by anthropogenic activities (vehicular traffic from Highway Bridge and thermal power plant). The distribution of heavy metals in sediment cores showed an upward enrichment in heavy metals with high concentration found in the uppermost may related to the increasing in human activities. The pollution indexes confirmed that the Tahaddart estuary sediment was considerably to high contaminated by heavy metals near to different anthropogenic inputs. Similarly, the potential ecological risk index and the biological risk index present 21% probability of toxicity posing potential risk to the aquatic organisms. These results provide basic information that can be used to protect and improve the quality of this ecosystem.     

N-acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma

The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.     

Histopathology Characteristics of two Different Benign Tumours in Capoeta capoeta

The aim of the present study was to determine the morphologic and histopathologic characteristics of tumors observed in samples from moribund Capoeta capoeta. For this purpose, ten fish, captured from the Fırat River located in southeastern Anatolia of Turkey, were examined for gross malformations and histopathological morphology. Externally, two different morphological types of tumours were detected in the anus region and on the ventral part of the operculum of one of the examined fish. In this study, tumours in a moribund fish were identified as benign because they were well differentiated, non-infiltrative and non-metastatic. In the histological examination, the external growth located in the ventral region of the operculum was characteristic of a papilloma showing exophytic inverted development. This is our first report on both melanomacrophage and green fibrils in the papilloma. The other observed pathological growth, covered with hemorrhagic skin and located near the anus, was characteristic of a benign tumour (subcutaneous lipoma) which constituted typical adipocytes. Thus, our study detected two different types of benign tumours in Capoeta capoeta, and it is the first time being reported in a cyprinid species