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Alzheimer’s disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid $\beta$-peptide (A$\beta$) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A$\beta$ cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A$\beta$-treated mammalian cells and $A\mathit{\beta }$42-expressing flies. Moreover, C. sativum extract intake suppressed $A\beta 42$-induced cell death in the larval imaginal disc and brain without affecting A$\beta$42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A$\beta$-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the $A\beta 42$-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.

The goal of this paper is to solve mathematical model equations on solid tumour growth and compute their parameter values by applying growth rates of prostate cancer cell lines in vivo. For these computations, we investigate previously developed C3(1)/Tag transgenic models of prostate cancer. To make the computations fast, we have constructed an algorithm, which is based on small amounts of spatial grid-points and obtained a correspondence between the in vivo growth of tumours and the solutions of the model equations.

Alendronate has been developed for the treatment of diseases characterized by increased bone resorption, such as osteoporosis. It increases metaphyseal bone density, bone volume, femoral bending strength and vertebral compressive strength, in a dose-dependent manner, in growing, intact rats. In ovariectomized (OVX) rats, alendronate increases femoral bone mass and tibial trabecular bone volume in a dose-dependent manner, and increases femoral midshaft bending strength. In rats immobilized by unilateral sciatic neurectomy, it inhibits bone loss and is dose-dependent. In rats, alendronate prevents high-turnover osteopenia induced by hyperthyroidism or by administration of immunosuppressant agent cyclosporin-A. Also in rats, treatment with prostaglandin E₂ and alendronate does not inhibit prostaglandin E₂-induced stimulation of bone formation on endocortical and periosteal surfaces. It does, however, prevent prostaglandin E₂-induced cortical bone porosity as a result of increased bone resorption, leading to an increase in cortical thickness and an increase in three-point bending strength of the femoral midshaft. At up to five times the dose used for treatment of osteoporosis in clinical trials, alendronate causes no abnormalities in bone remodeling, bone structure, or structural mechanical properties of the femur or vertebrae in intact beagles. Treatment with alendronate before or during fracture healing, or both, has no adverse effects on the union, strength, bone formation or mineralization of bone in mature beagle dogs. In intact minipigs, sodium fluoride increases and alendronate decreases bone turnover, while sodium fluoride, but not alendronate, decreases L4 strength and femoral stiffness. Small-angle X-ray scattering and backscattered electron imaging show that the trabecular bone matrix is more uniformly mineralized after alendronate treatment. In OVX baboons, which show bone changes similar to those seen in postmenopausal women, alendronate prevents an increase in bone turnover, and increases both bone volume and strength in vertebrae, in a dose-dependent manner. Alendronate also reduces the bone loss of alveolar support associated with periodontitis in monkeys. Thus, alendronate inhibits bone resorption and bone turnover, increases bone quantity accompanied by improved bone quality in some of the intact animals and in the animal models.

The aim of this study was to evaluate the validity of the model that could produce reproducible and persistent motor weakness and define the accurate tasks and testing parameters for longitudinal assessment of neurological deficits after traumatic brain injury (TBI). We compared the effects of two rat models that suffered different controlled cortical impact (CCI) injury, as well as extensive motor cortex resection model, on behavior recovery and brain morphology. Behavioral tests including the skilled reaching task, limb-use asymmetry test and the grasping test were employed to evaluate neurofunctional recovery from pre- to 12 weeks after the injury. The results demonstrated that all the rats in four groups showed spontaneous functional improvement with the past of time after surgery, especially in rats with mild and moderate CCI injury. At the end of the experiment, the animals' performance reached preoperative base lines on reaching task and limb-use asymmetry test in mild and moderate groups, while severe motor weakness could be observed in rats with severe CCI injury, as well as rats with extended motor cortex resection. Overall, the results of this study indicated that both models with severe CCI injury and extended resection of the motor cortex developed reproducible and long-lasting motor weakness, comparable in severity and duration and identified skilled reaching task, as well as limb-use asymmetry test, as sensitive assessments for slight neurological deficits after brain injury. This will help to provide the basis for further research of the processes after the TBI and development of novel therapies.

Shigella flexneri is a Gram-negative facultatively intracellular pathogen responsible for bacillary dysentery in humans. More than one million deaths occur yearly due to infections with Shigella spp. and the victims are mostly children of the developing world. The pathogenesis of Shigella centres on the ability of this organism to invade the colonic epithelium where it induces severe mucosal inflammation. Much information that we have gained concerning the pathogenesis of Shigella has been derived from the study of in vitro models of infection. Using these techniques, a number of the molecular mechanisms by which Shigella invades epithelial cells and macrophages have been identified. In vivo models of shigellosis have been hampered since humans are the only natural hosts of Shigella. However, experimental infection of macaques as well as the murine lung and rabbit ligated ileal loop models have been important in defining some of the immune and inflammatory components of the disease. In particular, the murine lung model has shed light on the development of systemic and local immune protection against Shigella infection. It would be naive to believe that any one model of Shigella infection could adequately represent the complexity of the disease in humans, and more sophisticated in vivo models are now necessary. These models require the use of human cells and tissue, but at present such models remain in the developmental stage. Ultimately, however, it is with such studies that novel treatments and vaccine candidates for the treatment and prevention of shigellosis will be designed.

Progress on lung stem cell bioprocessing and tissue engineering has been slow due to the lung's complex architecture and difficulties in differentiating stem cells toward the various pneumocytic lineages, in particular type II pneumocytes. Recent advances on the use of stem cells appear promising in providing a reliable supply of clinically relevant cell numbers of lung cells for potential therapeutic applications. The development of bioprocess technologies for the successful transfer of the current laboratory-based practice of stem cell and tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation, safety of the process and the product to be suitable for clinical applications. Furthermore, the utilisation of bioreactors addresses issues of mass transport and provides a three-dimensional growth environment. A variety of cell sources are being investigated for their suitability in generating lung epithelial cells. This review will discuss the complexity of the lung structure, evaluate the various cell sources, and present an up-to-date assessment of the bioreactor technology available that can contribute to the successful differentiation of stem cells into airway epithelial cells.

The estrogen receptor (ER) has proved to be an excellent target for the treatment and prevention of breast cancer. Although the majority (80%) of breast cancer is ER positive, not all ER positive tumors respond to antihormone therapy. When an ER positive tumor does not respond at all to antihormone therapy it is described to have intrinsic resistance. This contrasts with acquired antihormone resistance where the tumor initially responds with regression but then cell populations expand that grow because of tamoxifen or despite estrogen deprivation. Based on laboratory studies using ER positive cell lines, the evolution of acquired antihormone resistance has been documented. Growth factor pathways expand and subvert the action of the ER at the genome. The new knowledge about molecular mechanisms of resistance has created new opportunities for combinations of antihormone therapies and inhibitors of growth factor pathways.

The investigation of phenotypes in model organisms has the potential to reveal the molecular mechanisms underlying disease. The large-scale comparative analysis of phenotypes across species can reveal novel associations between genotypes and diseases. We use the PhenomeNET network of phenotypic similarity to suggest genotype–disease association, combine them with drug–gene associations available from the PharmGKB database, and infer novel associations between drugs and diseases. We evaluate and quantify our results based on our method's capability to reproduce known drug–disease associations. We find and discuss evidence that levonorgestrel, tretinoin and estradiol are associated with cystic fibrosis (p < 2:65 · 10⁻⁶, p < 0:002 and p < 0:031, Wilcoxon signedrank test, Bonferroni correction) and that ibuprofen may be active in chronic lymphocytic leukemia (p < 2:63 p < 0:03110⁻²³ Wilcoxon signed-rank test, Bonferroni correction). To enable access to our results, we implement a web server and make our raw data freely available. Our results are the first steps in implementing an integrated system for the analysis and prediction of drug–disease associations for rare and orphan diseases for which the molecular basis is not known.