Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

Background: The spread of tumors through neural routes is common in several types of cancer in which patients suffer from a moderate-to-severe neuropathy, neural damage and a distorted quality of life. Here we aim to examine the expression profiles of transient receptor potential vanilloid 1 (TRPV1) and of transient receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4) and extracellular signal-regulated kinase (ERK1/2), and to assess the possible therapeutic strategies through blockade of transient receptor potential (TRP) channels. Methods: Cancer was induced within the sciatic nerves of male Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and used for measurements of immunofluorescence and Western blotting. The TRPV1 antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the calcium ions inhibitor ruthenium red were used to treat thermal and/or mechanical hyperalgesia. Results: Transient receptor potential vanilloid 1 showed a lower expression in DRGs on days 7 and 14. The expression of TRPV4, TLR4 and ERK1/2 showed an increase on day 3 then a decrease on days 7 and 14. TRPV1 and TLR4 as well as TRPV4 and ERK1/2 co-existed on the same neuronal cells. The neuropathic pain was reversed in dose-dependent manners by using the TRP antagonists and the calcium ions inhibitor. Conclusion: The decreased expression of TRPV1 and TRPV4 is associated with high activation. The increased expression of TLR4 and ERK1/2 reveals earlier immune response and tumor progression, respectively, and their ultimate decrease is an indicator of nerve damage. We studied the possible role of TRPV1 and TRPV4 in transducing cancer-induced hyperalgesia. The possible treatment strategies of cancer-induced thermal and/or mechanical hyperalgesia using capsazepine, HC-067047 and ruthenium red are examined.Comment: PMID: 29637027, PMCID: PMC588970

Analyzing Digital Image by Deep Learning for Melanoma Diagnosis

Image classi cation is an important task in many medical applications, in order to achieve an adequate diagnostic of di erent le- sions. Melanoma is a frequent kind of skin cancer, which most of them can be detected by visual exploration. Heterogeneity and database size are the most important di culties to overcome in order to obtain a good classi cation performance. In this work, a deep learning based method for accurate classi cation of wound regions is proposed. Raw images are fed into a Convolutional Neural Network (CNN) producing a probability of being a melanoma or a non-melanoma. Alexnet and GoogLeNet were used due to their well-known e ectiveness. Moreover, data augmentation was used to increase the number of input images. Experiments show that the compared models can achieve high performance in terms of mean ac- curacy with very few data and without any preprocessing.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Theoretical investigations of β-tricalcium

Beta-tri-calcium phosphate (β-TCP) materials have gained a great deal of research considerations in biomaterial area due to their excellent biocompatibility and identical chemical compositions to the natural teeth and bones. Therefore, the β-TCP compound can be used as coatings, cement and composites as well as biocompatible ceramics for medical and dental applications. Electronic and optical properties for β-TCP compound have been investigated using density functional theory (DFT). For the calculations, we used full potential linear augmented plane wave method (FPLAPW), within three types of approximations along with local density approximations (LDA), generalized gradient approximations (GGA) and Modified Becke-Johnson (mBJ) to get the effect of the exchange and correlation in our calculations to get an accurate results. The computed band gap values for (β-TCP) compound using LDA, GGA, and mBJ-GGA approximations are 5.5 eV, 5.9 eV and 6.8 eV respectively. This is also predicted that the chemical bonding in this compound is a kind of combination of covalent and ionic character that is in a line with the experimental findings. The optical parameter, static dielectric constant ε1(0) reaches the values of 3.23681 (eV) at 0 GPa for the β-TCP compound. The obtained results are of vital nature for rising the quality of the electronic and optical properties of this material, and provide more evidence to fabricate novel Beta-Tri-calcium phosphate biomaterials for medical and dental applications

Density functional theory study of the electronic and optical properties of pure and magnesium doped Β-tricalcium phosphate compound

β-Tri-calcium phosphate material (β-TCP), have attract a wide interest in the material science and medical science applications, due to its excellent biocompatibility and its identical chemical compositions to the natural teeth and bones. For that reason, (β-TCP) compound is widely used as biocompatible ceramics in medical and dental science applications. However, research shows that, pure β-TCP material has lower ability to stimulate the growth of natural bone and teeth as needed. Therefore, in order to address this deficiency magnesium impurity is used to replace calcium in the matrix of pure β-TCP to enhance its electronic and optical properties which are not present in the pure one. Thereby, its biological performance becomes improved. By changing the chemical composition of β-TCP to be similar to the mineral compositions of the natural teeth and bones. This will give more insight in fabrication of biomaterial devices for replacing, repairing and rebuilding the broken or damaged human teeth and bones. Here, we present the study of compound β-TCP using density functional theory (DFT). For the calculations, we used full potential linear augmented plane wave method (FPL-APW), along with generalized gradient approximations (GGA) potential. The band gap values of 5.2 eV and 3.4 eV are obtained for the pure and Mg-doped β-TCP, respectively. These results are in good agreement with the experimental values. Our results show peaks which correspond to the refractive index, complex dielectric function, optical conductivity, optical reflectivity, extinction coefficient, absorption efficient, and electron energy loss. These peaks are shifted towards the higher energy values for the pure and Mg-doped β-TCP material. The obtained results have more significance for increasing the quality of electronic and optical properties of this material and offer more evidences to synthesize enhanced β-TCP material for dental and medical applications

Application of simulated annealing to solve multi-objectives for aggregate production planning

Aggregate production planning (APP) is one of the most significant and complicated problems in production planning and aim to set overall production levels for each product category to meet fluctuating or uncertain demand in future and to set decision concerning hiring, firing, overtime, subcontract, carrying inventory level. In this paper, we present a simulated annealing (SA) for multi-objective linear programming to solve APP. SA is considered to be a good tool for imprecise optimization problems. The proposed model minimizes total production and workforce costs. In this study, the proposed SA is compared with particle swarm optimization (PSO). The results show that the proposed SA is effective in reducing total production costs and requires minimal time

Developing Sustainable Leadership Practices in Saudi Arabian Universities: A Comparative Study between Public and National Universities

This study examines sustainable leadership practices in Saudi Arabian universities, comparing public and national universities. A mixed-methods approach was employed, utilizing a questionnaire administered to 235 academic leaders (160 from public universities and 75 from national universities) and semi-structured interviews with 8 university vice presidents and deputies. The research identified key sustainable leadership practices and assessed their prevalence in both types of universities. Findings revealed that overall sustainable leadership practices were at a medium level in public universities (M=3.61, SD=0.57) and a high level in national universities (M=3.80, SD=0.50). Environmental contribution emerged as the top responsible factor in both sectors, while innovation and creativity stood as the least responsible factor. Significant differences were found between public and national universities in most dimensions, favoring national universities while there was no significant difference in social responsibility and environmental contribution made by both categories of universities. The study found out the following strategies that can build up, the practice of sustainable leadership, both sectors recognized the importance of training programs and performance evaluation standards. These findings provide important knowledge about sustainable leadership in higher education settings in the Saudi Arabian context and recommendations that can be useful to future research and practice for policymakers and university administrators to better develop sustainable leadership

Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan

The present investigation was directed to study the possible chemoprotective activity of orally administered quercetin against topotecan-induced cyto- and genotoxicity towards mouse somatic cells in vivo. DNA strand breaks, micronuclei formation, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Oxidative stress markers such as intracellular reactive oxygen species generation, lipid peroxidation, and reduced and oxidized glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses tested. Pretreatment of mice with quercetin significantly reduced topotecan-induced genotoxicity and cytotoxicity in bone marrow cells, and these effects were dose dependent. Moreover, prior administration of quercetin ahead of topotecan challenge ameliorated oxidative stress markers. In conclusion, quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan

How Zinc Transporters in Escherichia coli Influence Ageing in the Nematode Caenorhabditis elegans

Gut microbes play an important role in mammalian physiology. Escherichia coli not only provide the Caenorhabditis elegans with vital nutrients but also influence worms lifespan. Studying such interactions could help us to understand how intestinal microbes influence mammalian ageing. A recent gene deletion study of 1041 E. coli in our lab identified 9 genes that are involved in the increase of worm’s lifespan. One gene identified was ZnuB, which forms part of the high affinity znuABC zinc ABC transporters, plays an important role in zinc homeostasis, and has been suggested to play a role in increased lifespan. To validate this hypothesis, levels of zinc were measured using ICP-MS in znuA, znuB, and znuC mutant bacteria and worms fed with the mutants, and compared with zinc levels in WT bacteria and C. elegans fed with WT bacteria. Zinc levels were also measured in LB and NGM media. It was found that although bacteria and worms could obtain zinc from LB media, the level of zinc was lower in worms and the three mutant bacteria than in WT bacteria alone. Lifespan of worms fed with those mutants was investigated. Worms fed with znuB and znuC bacteria showed extended lifespan, compered to worms fed with znuA bacteria. Reduced fecundity was observed in experimental worms fed with mutant as compared to worms fed with WT bacteria. Moreover, the worms fed with the znuB showed a delay in the reproductive cycle. These results suggest that reducing zinc concentration itself in the mutant bacteria does not make the worms live longer, but the mutation in the znuB could produce different effects. Results of zinc supplement experiments using mutants showed reversal effect on worm developmental delay when fed with znuB and zinc supplements. These results show that the znuB not only plays an important role in zinc uptake by bacteria, but also affects the lifespan of C. elegans