The c-Jun NH2-terminal kinase (JNK) pathway represents one subgroup of MAP kinases that are activated primarily by cytokines and exposure to environmental stress. Autophagy is a protein-degradation ...system characterized by the formation of double-membrane vacuoles termed autophagosomes. Autophagy-related gene beclin 1 plays a key role in autophagosome formation. However, the relationships between activation of JNK pathway, autophagy induction and Beclin 1 expression remain elusive. In this study, we used human cancer cell lines CNE2 and Hep3B to investigate the role of JNK-mediated Beclin 1 expression in ceramide-induced autophagic cell death. Ceramide-treated cells exhibited the characteristics of autophagy (that is, acidic vesicular organelle formation and the LC3-II generation). JNK was activated in these two cell lines exposed to ceramide and the phosphorylation of c-Jun also increased. In the meantime, we found that ceramide upregulated Beclin 1 expression in cancer cells. The upregulation of Beclin 1 expression could be blocked by SP600125 (a specific inhibitor of JNK) or a small interfering RNA (siRNA) directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase reporter analysis revealed that c-Jun was involved in the regulation of beclin 1 transcription in response to ceramide treatment. In addition, inhibition of JNK activity by SP600125 could inhibit autophagy induction by ceramide. Furthermore, Beclin 1 knockdown by siRNA also inhibited ceramide-mediated autophagic cell death. JNK-mediated Beclin 1 expression was also observed in topotecan-induced autophagy. These data suggest that activation of JNK pathway can mediate Beclin 1 expression, which plays a key role in autophagic cell death in cancer cells.
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric ...cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-κB and STAT3 signaling, while NF-κBp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.
Electronic medical records are emerging as a major source of data for clinical and translational research studies, although phenotypes of interest need to be accurately defined first. This article ...provides an overview of how to develop a phenotype algorithm from electronic medical records, incorporating modern informatics and biostatistics methods.
An elevated DNA-repair capacity in cancer cells leads to radiation resistance and severely limits the efficacy of radiation therapy. Activation of Akt is tightly associated with resistance to ...radiotherapy, and Mre11 protein has important role during the repair of DNA double-strand breaks (DSBs). In this report, our results showed that inhibition of Akt activity impaired the repair of DSBs in CNE2 cells, whereas activated Akt promoted the repair of DSBs in HeLa cells. Knockdown of Mre11 also impaired the process of DSB repair in both these two cell lines. More importantly, we found that Akt could regulate Mre11 expression. Inhibition of Akt activity by small interfering RNA or LY294002 efficiently downregulated the Mre11 expression in CNE2 cells, and transfection with myr-Akt plasmid in HeLa cells upregulated the Mre11 expression. In addition, luciferase reporter analysis revealed that Mre11 reporter activity increased after transfection with myr-Akt1 plasmids, and this myr-Akt1-induced transcriptional activity was blocked in the presence of LY294002. Further study showed GSK3β/β-catenin/LEF-1 pathway was involved in this regulation. Knockdown of β-catenin or LEF-1 led to the downregulation of Mre11, whereas overexpression of β-catenin led to upregulation of Mre11. The chromatin immunoprecipitation assay assay showed β-catenin/LEF-1 heterodimer could directly bind to the promoter of Mre11 in vivo. And the luciferase activity of the pGL3-Mre11 and pGL3-Lef increased in HeLa cells following β-catenin plasmid co-transfected, but was abolished when the LEF-1-binding conserved sequences of Mre11 promoter were mutated. These results together support Akt can upregulate the expression of Mre11 through GSK3β/ β-catenin/LEF pathway to elevate DSB-repair capacity in cancer cells.
As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public ...data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach reduces confounding with population structure and increases power compared to standard genome-wide association methods. Sixteen novel loci were found, including an association between Chromomethylase 2 (CMT2) and temperature seasonality where the genome-wide CHH methylation was different for the group of accessions carrying the plastic allele. Cmt2 mutants were shown to be more tolerant to heat-stress, suggesting genetic regulation of epigenetic modifications as a likely mechanism underlying natural adaptation to variable temperatures, potentially through differential allelic plasticity to temperature-stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this ambispective study was to investigate whether deep learning-based automatic segmentation and landmark detection, the SkullEngine, could be used for orthognathic surgical planning. ...Sixty-one sets of cone beam computed tomography (CBCT) images were automatically inferred for midface, mandible, upper and lower teeth, and 68 landmarks. The experimental group included automatic segmentation and landmarks, while the control group included manual ones that were previously used to plan orthognathic surgery. The qualitative analysis of segmentation showed that all of the automatic results could be used for computer-aided surgical simulation. Among these, 98.4% of midface, 70.5% of mandible, 98.4% of upper teeth, and 93.4% of lower teeth could be directly used without manual revision. The Dice similarity coefficient was 96% and the average symmetric surface distance was 0.1 mm for all four structures. With SkullEngine, it took 4 minutes to complete the automatic segmentation and an additional 10 minutes for a manual touchup. The results also showed the overall mean difference between the two groups was 2.3 mm for the midface and 2.4 mm for the mandible. In summary, the authors believe that automatic segmentation using SkullEngine is ready for daily practice. However, the accuracy of automatic landmark digitization needs to be improved.
Petroleum-based polymers have raised significant environmental concerns. It is critical to create compostable, good biocompatibility, and nontoxic polymers to replace petroleum-based polymers. Thus, ...this research was performed to extract the gelatin from fish waste cartilage and coated it over the surface of spherical shaped pre-synthesized ZnNPs along with a suitable plasticizer to produce the biodegradable film. The presence of gelatin on the surface of ZnNPs was first confirmed using UV–visible spectrophotometers, as well as the characteristic functional groups involved in the coating were investigated using Fourier-Transform Infrared Spectroscopy (FTIR). The morphological appearance of gelatin coated ZnNPs was ranged from 41.43 to 52.31 nm, the shape was found as platonic to pentagonal shape, and the fabricated film was observed through Scanning Electron Microscope (SEM). The thickness, density, and tensile strength of fabricated film were found to be 0.04–0.10 mm, 0.10–0.27 g/cm3, and 31.7 kPa. These results imply that the fish waste cartilage gelatin coated ZnNPs-based nanocomposite can be used for film preparation as well as a wrapper for food and pharmaceutical packaging.
•Gelatin has been harvested successfully from fish waste cartilage.•The gelatin effectively coated the ZnNPs, resulting in the formation of a nanocomposite.•The size of the gelatin coated ZnNPs was found as 41.43–52.31 nm & platonic shape.•Thickness & density of the fabricated film were found as 0.10 mm & 0.27 g/cm3.•The tensile strength of the gelatin-coated ZnNPs-based biodegradable film was 31.7 kPa.
The starch is one of the most essential food stuff and serves as a raw material for number of food products for the welfare of human. During the production process enormous volume of effluents are ...being released into the environment. In this regard, this study was performed to evaluate the physicochemical traits of Manihot esculenta processing effluent and possible sustainable approach to treat this issue using Eichhornia crassipes based biochar. The standard physicochemical properties analysis revealed that the most the parameters (EC was recorded as 4143.17 ± 67.12 mhom−1, TDS: 5825.62 ± 72.14 mg L−1, TS: 7489.21 ± 165.24 mg L−1, DO: 2.12 ± 0.21 mg L−1, BOD 2673.74 ± 153.53 mg L−1, COD: 6672.66 ± 131.21 mg L−1, and so on) were beyond the permissible limits and which can facilitate eutrophication. Notably, the DO level was considerably poor and thus can support the eutrophication. The trouble causing E. crassipes biomass was used as raw material for biochar preparation through pyrolysis process. The temperature ranging from 250 to 350 °C with residence time of 20–60 min were found as suitable temperature to provide high yield (56–33%). Furthermore, 10 g L−1 concentration of biochar showed maximum pollutant adsorption than other concentrations (5 g L−1 and 15 g L−1) from 1 L of effluent. The suitable temperature required to remediate the pollutants from the effluent by biochar was found as 45 °C and 35 °C at 10 g L−1 concentration. These results conclude that at such optimized condition, the E. crassipes effectively adsorbed most of the pollutants from the M. esculenta processing effluent. Furthermore, such pollutants adsorption pattern on biochar was confirmed by SEM analysis.
•M. esculenta effluent contain increased quantity of physicochemical properties.•E. crassipes biomass effectively converted as biochar at 250–350 °C with 20–60 min.•10 g L−1 concentration of biochar was found as sufficient for 1 L of effluent.•Maximum remediation by adsorption was found at 45 °C and followed by 35 °C.•SEM analysis confirmed pollutants adsorption on porous structure of biochar.
Nannochloropsis microalgae biochar has become increasingly attractive due to its potential as a component of microalgae-based biodiesel blends. This biochar is a by-product of the pyrolysis process, ...but its use in the energy sector has been limited. In this study, pellets were formed using microalgae residues and their physiochemical properties were analyzed to assess the feasibility of using microalgae biochar as a fuel source. Three types of biomasses, namely date seed dust, coconut shell waste, and microalgae biochar, were utilized to produce fuel pellets. These pellets were categorized into three types, B1, B2, and B3, based on the composition of the biomass. The inclusion of microalgae biochar in the pellets resulted in enhanced calorific value, as well as improved heating value and bulk density. Moreover, the mechanical strength of microalgae-based pellets was higher due to their high lignin content compared to another biomass. The moisture absorption test results showed that the use of mixed biomass reduced the moisture content over an extended period. Microalgae pellets exhibited higher young's modulus and greater impact resistance, indicating greater mechanical strength. Furthermore, due to their higher calorific value, the combustion time of microalgae pellets was greater than that of other biomass. In conclusion, the results of this study suggest that microalgae biochar can be a promising alternative fuel source for the energy sector.
•Nannochloropsis microalgae biochar was produced using microwave assisted pyrolysis.•Date seed dust, coconut shell waste, and microalgae biochar were utilized to produce fuel pellets.•Inclusion of microalgae biochar in the pellets resulted in enhanced calorific value, heating value, and bulk density.•Microalgae biochar can be a promising alternative fuel source for the energy sector.
Scavenging or quenching of the reactive oxygen species (ROS) involved in oxidative stress has been the subject of many recent studies. Resveratrol, found in various natural food products, has been ...linked to decreased coronary artery disease and preventing cancer development. The present study measured the effect of resveratrol on several different systems involving the hydroxyl, superoxide, metal/enzymatic-induced, and cellular generated radicals. The rate constant for reaction of resveratrol with the hydroxyl radical was determined, and resveratrol was found to be an effective scavenger of hydroxyl, superoxide, and metal-induced radicals as well as showing antioxidant abilities in cells producing ROS. Resveratrol exhibits a protective effect against lipid peroxidation in cell membranes and DNA damage caused by ROS. Resveratrol was also found to have a significant inhibitory effect on the NF-κB signaling pathway after cellular exposure to metal-induced radicals. It was concluded that resveratrol in foods plays an important antioxidant role.
PDF
