Zobrazení zdroje stránky Macgregorlauritsen5214

They produced three different drafts on the three thematic areas of the project. The sub-committees are 1. Sub-committee on Fellowship, Training and Research Curriculum. 2. Sub-committee on Standard Protocols and Management Guidelines. 3. Sub-committee of the Nigerian Neurotrauma Registry CONCLUSION The Committee concluded that a formal protocol for neurotrauma care is long overdue in Nigeria for the standardization of all aspects of neurotrauma. It then recommended the adoption of these guidelines by all institutions offering services in Nigeria using the management protocols, opening a registry and mounting researches on the various aspects of neurotrauma. Matrix metalloproteinases (MMPs) are zinc-dependent extracellular matrix remodeling endopeptidases. MMPs cleave various matrix proteins such as collagen, elastin, gelatin and casein. MMPs are often implicated in pathological processes, such as cancer progression including metastasis. Meanwhile, microorganisms produce various secondary metabolites having unique structures. We designed and synthesized dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of epoxyquinomicin C derived from Amycolatopsis as an inhibitor of NF-κB. This compound inhibited cancer cell migration and invasion. Since DHMEQ is comparatively unstable in the body, we designed and synthesized a stable DHMEQ analog, SEMBL. SEMBL also inhibited cancer cell migration and invasion. We also looked for inhibitors of cancer cell migration and invasion from microbial culture filtrates. As a result, we isolated a known compound, ketomycin, from Actinomycetes. DHMEQ, SEMBL, and ketomycin are all NF-κB inhibitors, and inhibited the expression of MMPs in the inhibition of cellular migration and invasion. These are all compounds with comparatively low toxicity, and may be useful for the development of anti-metastasis agents. Only recently it was discovered that haemoglobin (Hb) belongs to the standard gene repertoire of insects, although their tracheal system is used for respiration. A classical oxygen-carrying function of Hb is only obvious for hexapods living in hypoxic environments. In other insect species, including the common fruit fly Drosophila melanogaster, the physiological role of Hb is yet unclear. Here, we study recombinant haemoglobin from the European honeybee Apis mellifera (Ame) and the malaria mosquito Anopheles gambiae (Aga). Spectroscopic evidence shows that both proteins can be classified as hexacoordinate Hbs with a strong affinity for the distal histidine. AgaHb1 is proposed to play a role in oxygen transport or sensing based on its multimeric state, slow autoxidation, and small but significant amount of five-coordinated haem in the deoxy ferrous form. AmeHb appears to behave more like vertebrate neuroglobin with a complex function given its diversified distribution in the genome. BACKGROUND Actionable somatic molecular alterations are found in 15 to 20% of non-small cell lung cancer (NSCLC) in the Caucasians. NSCLC is a tumor observed in patients with germline-variants causing Li-Fraumeni syndrome (LFS), but its somatic molecular profile is unknown. METHODS Retrospective study of clinical and molecular profile of NSCLC in patients with germline-TP53 variants. RESULTS In 22 NSCLC patients with LFS (n=23 lung tumors), 64% were female, median age 51, 74% non-smokers, 73% with adenocarcinoma histology and 84% were diagnosed with advanced stage disease. These 22 patients harbor 16 distinct germline TP53 variants; the most common was p.R158H (5/22; 3 in the same family). Personal and familiar history of cancer was reported in 71% and 90% of patients, respectively. Lung cancer was in most of the cases (87%, 13/15) a late-onset diagnosis. Among the 21 tumors analyzed, somatic oncogenic driver mutations were found in 19/21 (90%), 18 EGFR-mutations (exon-19 deletions in 12 cases, L858R in 3 cases and G719A, exon-20 insertion, missing mutation subtype, each in one case) and one case with ROS1 fusion. A PI3KCA mutation was concurrently detected at diagnosis in 3 EGFR exon 19 deletion tumors (3/12). The median OS was 37.3 months in 14 patients treated with EGFR-inhibitors; 7 developed resistance, 5 (71%) with acquired EGFR-T790M mutation and one with SCLC transformation. CONCLUSION Driver oncogenic alterations were observed in 90% of the LFS tumors, mainly EGFR mutations but also one ROS1 fusion. The germline-TP53 variants and lung cancer carcinogenesis driven by oncogenic processes needs further evaluation. In the last 10 years a deeper understanding of the immune landscape of cancers, including immune-evasion processes, has allowed the development of a new class of agents. The re-activation of host anti-tumor immune response, offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) immune-checkpoint inhibitors (ICI), both as single agents and in combination with chemotherapy, and more recently combination of ICI, anti-PD1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, have led to breakthrough therapeutic advances for patients with advanced non-small cell lung cancer (NSCLC) and to a lesser extent, patients with small cell lung cancer (SCLC). Encouraging activity has recently emerged in pre-treated patients with thymic carcinoma. Conversely in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive eff, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice, and elucidate future treatment strategies and research priorities. BACKGROUND Single port laparoscopic hepatectomy has been applied in some surgeries. We aimed to describe our experience with single port laparoscopic left lateral sectionectomy (SPLS) and to compare the safety and feasibility of this technique with those of conventional multi-port laparoscopic left lateral sectionectomy (MPLS) in the treatment of hepatocellular carcinoma (HCC). METHODS A total of 72 consecutive patients who underwent SPLS (n&nbsp;=&nbsp;33) and MPLS (n&nbsp;=&nbsp;39) for HCC were enrolled. The peri-operative parameters of safety and feasibility, as well as the short-term oncological outcomes were compared. RESULTS The length of postoperative hospital stay (LOS) was significantly shorter in the SPLS group than in the MPLS group (4.12 vs. 4.59 days, P&nbsp;=&nbsp;0.043). No significant difference between the two groups was found in the operation time (104.58 vs. 95.69&nbsp;min in the SPLS group and MPLS group respectively, P&nbsp;=&nbsp;0.353) or the amount of blood loss (62.73 vs. 68.46&nbsp;ml, P&nbsp;=&nbsp;0.595). The 1-year recurrence-free survival rate was 77.9% in the SPLS group and 70.7% in the MPLS group (P&nbsp;=&nbsp;0.82). Subgroup analysis showed that for patients without cirrhosis, the LOS was shorter in the SPLS group than in the MPLS group (P&nbsp;=&nbsp;0.033), while for patients with cirrhosis, the LOS was not significantly different between the two groups (P&nbsp;=&nbsp;0.201), although it was shorter in the SPLS group. CONCLUSIONS SPLS was a feasible and safe surgical approach for the treatment of HCC on left lateral section. Children with malformations of cortical development (MCD) are at risk for epilepsy, developmental delays, behavioral disorders, and intellectual disabilities. While for a subset of these children epilepsy surgery may result in seizure freedom, there are limited options for treating or curing the other conditions, and epilepsy surgery is not an option in all cases. Understanding the genetic and neurobiological mechanisms underlying MCD is a necessary step in elucidating novel therapeutic targets. The tish (telencephalic internal structural heterotopia) rat is a unique model of MCD with spontaneous seizures, but the underlying genetic mutation(s) have remained unknown. DNA and RNA-sequencing revealed that a deletion encompassing a previously unannotated first exon markedly diminished Eml1 transcript and protein abundance in the tish brain. Developmental electrographic characterization of the tish rat revealed the early-onset spontaneous spike-wave discharge (SWD) bursts beginning at postnatal day (P) 17. A dihybrid cross demonstrated that the mutant Eml1 allele segregates with the observed dysplastic cortex and the early-onset SWD bursts in monogenic autosomal recessive frequencies. Our data link the development of the bilateral, heterotopic dysplastic cortex of the tish rat to a deletion in Eml1. Amyotrophic lateral sclerosis (ALS) is a fatal late-onset neurodegenerative disease that specifically affects the function and survival of spinal and cortical motor neurons. ALS shares many genetic, clinical, and pathological characteristics with frontotemporal dementia (FTD), and these diseases are now recognized as presentations of a disease spectrum known as ALS/FTD. The molecular determinants of neuronal loss in ALS/FTD are still debated, but the recent discovery of nucleocytoplasmic transport defects as a common denominator of most if not all forms of ALS/FTD has dramatically changed our understanding of the pathogenic mechanisms of this disease. Loss of nuclear pores and nucleoporin aggregation, altered nuclear morphology, and impaired nuclear transport are some of the most prominent features that have been identified using a variety of animal, cellular, and human models of disease. Here, we review the experimental evidence linking nucleocytoplasmic transport defects to the pathogenesis of ALS/FTD and propose a unifying view on how these defects may lead to a vicious cycle that eventually causes neuronal death. A substantial body of research now implicates the circadian clock in the regulation of an array of diverse biological processes including glial function, metabolism, peripheral immune responses, and redox homeostasis. Sleep abnormalities and other forms of circadian disruption are common symptoms of aging and neurodegeneration. [https://www.selleckchem.com/products/cx-5461.html CX-5461 cell line] Circadian clock disruption may also influence the aging processes and the pathogenesis of neurodegenerative diseases. The specific mechanisms governing the interaction between circadian systems, aging, and the immune system are still being uncovered. Here, we review the evidence supporting a bidirectional relationship between aging and the circadian system. Further, we explore the hypothesis that age-related circadian deterioration may exacerbate multiple pathogenic processes, priming the brain for neurodegeneration. Phospholipase A2 (PLA2) enzymes are small lipolytic hydrolases that can regulate immune responses through generation of Arachidonic Acid (AA), a precursor molecule of lipid mediators like prostaglandins, leukotrienes and thromboxanes. One of the family members of PLA2, secretory Phospholipase A2 Group IIA (PLA2G2A), was associated with different types of malignancies including prostate cancer. Elevated serum levels of PLA2G2A was found in prostate cancer (PCa) patients and associated with increased tumor grade in literature. 5'UTR regions have regulatory role in protein expression by controlling the accessibility of factors necessary for the translation initiation. Single nucleotide polymorphisms at 5'UTR regions have the potential to affect mRNA translation efficiency resulting in altered protein levels depending on structure and nucleotide content. Given that the 5'UTR polymorphism in PLA2G2A gene (rs11573156) is associated with increased serum levels of PLA2G2A, the association of this 5'UTR polymorphism with PCa susceptibility and metastasis was investigated in this study.