Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism

Targeted therapies are the most attractive options in the treatment of different tumours, including kidney cancers. Such therapies have entered a golden era due to advancements in research, breakthroughs in scientific knowledge, and a better understanding of cancer therapy mechanisms, which significantly improve the survival rates and life expectancy of patients. The use of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) as an anticancer therapy has attracted the attention of the scientific community and created great excitement due to its selectivity in targeting cancerous cells with no toxic impacts on normal tissues. However, clinical studies disappointingly showed the emergence of resistance against TRAIL. This study aimed to employ curcumin to sensitise TRAIL-resistant kidney cancerous ACHN cells, as well as to gain insight into the molecular mechanisms of TRAIL sensitization. Curcumin deregulated the expression of apoptosis-regulating micro Ribonucleic Acid (miRNAs), most notably, let-7C. Transfecting ACHN cells with a let-7C antagomir significantly increased the expression of several cell cycle protein, namely beta (β)-catenin, cyclin dependent kinase (CDK)1/2/4/6 and cyclin B/D. Further, it overexpressed the expression of the two key glycolysis regulating proteins including hypoxia-inducible factor 1-alpha (HIF-1α) and pyruvate dehydrogenase kinase 1 (PDK1). Curcumin also suppressed the expression of the overexpressed proteins when added to the antagomir transfected cells. Overall, curcumin targeted ACHN cell cycle and cellular metabolism by promoting the differential expression of let-7C. To the best of our knowledge, this is the first study to mechanistically report the cancer chemosensitisation potential of curcumin in kidney cancer cells via induction of let-7C.     

11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value

Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. ¹⁸F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[¹¹C]- methionine (MET), suggest higher sensitivity than ¹⁸F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of ¹FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.     

Advanced and Intelligent Control Techniques Applied to the Drive Control and Path Tracking Systems on a Robotic Wheelchair

This paper presents the theoretical support and experimental results of the application of advanced and intelligent control techniques to the drive control and trajectory tracking systems on a robotic wheelchair. The adaptive optimal control of the differential drive helps to improve the automatic guidance system's safety and comfort taking into consideration operating conditions such as load and distribution changes or motion actuator limitations. Furthermore, the incorporation of an optimal controller to minimize location errors and a fuzzy controller to adapt the linear velocity to the characteristics of the trajectory, provide the vehicle with a high degree of intelligence and autonomy, even when faced with obstacles. The global control solution implemented increases the features of the wheelchair for handicapped people, especially for those with a high degree of disability.     

Random 3-SAT: The Plot Thickens

This paper presents an experimental investigation of the following questions: how does the average-case complexity of random 3-SAT, understood as a function of the order (number of variables) for fixed density (ratio of number of clauses to order) instances, depend on the density? Is there a phase transition in which the complexity shifts from polynomial to exponential in the order? Is the transition dependent or independent of the solver? Our experiment design uses three complete SAT solvers embodying different algorithms: GRASP, CPLEX, and CUDD. We observe new phase transitions for all three solvers, where the median running time shifts from polynomial in the order to exponential. The location of the phase transition appears to be solver-dependent. GRASP shifts from polynomial to exponential complexity near the density of 3.8, CPLEX shifts near density 3, while CUDD exhibits this transition between densities of 0.1 and 0.5. This experimental result underscores the dependence between the solver and the complexity phase transition, and challenges the widely held belief that random 3-SAT exhibits a phase transition in computational complexity very close to the crossover point.     

Inactivation of Escherichia coli in milk by high-hydrostatic-pressure treatment in combination with antimicrobial peptides

We studied the inactivation in milk of four Escherichia coli strains (MG1655 and three pressure-resistant mutants isolated from MG1655) by high hydrostatic pressure, alone or in combination with the natural antimicrobial peptides lysozyme and nisin and at different temperatures (10 to 50 degrees C). Compared with that of phosphate buffer, the complex physicochemical environment of milk exerted a strong protective effect on E. coli MG1655 against high-hydrostatic-pressure inactivation, reducing inactivation from 7 logs at 400 MPa to only 3 logs at 700 MPa in 15 min at 20 degrees C. An increase in lethality was achieved by addition of high concentrations of lysozyme (400 microg/ml) and nisin (400 IU/ml) to the milk before pressure treatment. The additional reduction amounted maximally to 3 logs in skim milk at 550 MPa but was strain dependent and significantly reduced in 1.55% fat and whole milk. An increase of the process temperature to 50 degrees C also enhanced inactivation, particularly for the parental strain, but even in the presence of lysozyme and nisin, a 15-min treatment at 550 MPa and 50 degrees C in skim milk allowed decimal reductions of only 4.5 to 6.9 for the pressure-resistant mutants. A substantial improvement of inactivation efficiency at ambient temperature was achieved by application of consecutive, short pressure treatments interrupted by brief decompressions. Interestingly, this pulsed-pressure treatment enhanced the sensitivity of the cells not only to high pressure but also to the action of lysozyme and nisin.     

Advances in Wine Aging Technologies for Enhancing Wine Quality and Accelerating Wine Aging Process

Wine aging is an important process to produce high-quality wines. Traditionally, wines are aged in oak barrel aging systems. However, due to the disadvantages of the traditional aging technology, such as lengthy time needed, high cost, etc., innovative aging technologies have been developed. These technologies involve aging wines using wood fragments, application of micro-oxygenation, aging on lees, or application of some physical methods. Moreover, wine bottling can be regarded as the second phase of wine aging and is essential for most wines. Each technology can benefit the aging process from different aspects. Traditional oak barrel aging technology is the oldest and widely accepted technology. The application of wood fragments and physical methods are promising in accelerating aging process artificially, while application of micro-oxygenation and lees is reliable to improve wine quality. This paper reviews recent developments of the wine aging technologies. The impacts of operational parameters of each technology on wine quality during aging are analyzed, and comparisons among these aging technologies are made. In addition, several strategies to produce high-quality wines in a short aging period are also proposed.     

High-entropy alloys fabricated via powder metallurgy. A critical review

High-entropy alloys (HEAs) have attracted a great deal of interest over the last 14 years. One reason for this level of interest is related to these alloys breaking the alloying principles that have been applied for many centuries. Thus, HEAs usually possess a single phase (contrary to expectations according to the composition of the alloy) and exhibit a high level of performance in different properties related to many developing areas in industry. Despite this significant interest, most HEAs have been developed via ingot metallurgy. More recently, powder metallurgy (PM) has appeared as an interesting alternative for further developing this family of alloys to possibly widen the field of nanostructures in HEAs and improve some capabilities of these alloys. In this paper, PM methods applied to HEAs are reviewed, and some possible ways to develop the use of powders as raw materials are introduced.