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Franco posted an update 9 months ago
NGS revealed TP53 as the most frequently mutated gene. The rate of HER2 positive cases and MSI-H cases were 9.5% (4/42) and 12.2% (5/41), respectively. Among these 42 cases, there was no molecular and clinicopathological differences according to the presence of tumor cells with clear cytoplasm. Enteroblastic marker-positive CRC could be grouped together as CAED regardless of clear cell cytoplasm. By this definition, the frequency of CAED is 4.0%, and it has a poorer prognosis than that for conventional CRCs. HER2 targeting therapy would be a meaningful treatment for CAED, and CAEDs contain both MSI-H and MSI-stable CRCs, although MSS phenotype is dominant.In this study, methacrylation of alginate was carried out by reacting sodium alginate with methacrylic anhydride in the presence of sodium hydroxide (NaOH). Separately synthesized nano-hydroxyapatite (n-HA) powder was surface functionalized using mercaptopropionic acid (MPA) and EGMP (Ethylene Glycol Methacrylate Phosphate) in the presence of Azobisisobutyronitrile benzene (AIBN) as a free radical initiator in a nitrogen atmosphere. Methacrylated alginate solution was mixed with the required amount of surface functionalized HAp nanoparticles in the presence of 0.05% irgacure as photoinitiator and was placed at the centre ofa 8 KW of UV light source of 265 nm to prepare photocrosslinked bone paste.XRD analysis indicated that surface functionalization did not alter phase purity of hydroxyapatite nanopowder in the prepared paste. The graft polymerization of EGMP on the surface of HAp was confirmed by the presence of 1732 cm-1 band which belongs to C=O stretching of EGMP, in addition to the characteristic peaks of nano HAp and alginate in the composite paste. Storage modulus and loss modulus of all the prepared pastes increased non-linearly with time upto 100s exhibiting its pseudo plastic behaviour. The rate of release of BMP2 was significantly faster in the first few days, and the release curve gradually levelled off prior to slowing down upto 22 days. Mesenchymal stem cell adhesion studies revealed that cells could attach to the paste material and stretch over the surface of the material after 14days of incubation. MTT assay showed that prepared paste materials were conducive to mesenchymal stem cells attachment and proliferation. Immunocytochemistry analysis revealed that addition of surface functionalized nano HAp and BMP2 to alginate hydrogel enhanced osteogenic potential of the prepared paste. The result indicated that the newly developed photocrosslinked paste may be physically and biologically suitable for application as bone filler.Fuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy and the leading indication for corneal transplantation worldwide. FECD is characterized by the progressive decline of corneal endothelial cells (CECs) and the formation of extracellular matrix (ECM) excrescences in Descemet’s membrane (DM), called guttae, that lead to corneal edema and loss of vision. FECD typically manifests in the fifth decades of life and has a greater incidence in women. FECD is a complex and heterogeneous genetic disease where interaction between genetic and environmental factors results in cellular apoptosis and aberrant ECM deposition. In this review, we will discuss a complex interplay of genetic, epigenetic, and exogenous factors in inciting oxidative stress, auto(mito)phagy, unfolded protein response, and mitochondrial dysfunction during CEC degeneration. Specifically, we explore the factors that influence cellular fate to undergo apoptosis, senescence, and endothelial-to-mesenchymal transition. These findings will highlight the importance of abnormal CEC-DM interactions in triggering the vicious cycle of FECD pathogenesis. We will also review clinical characteristics, diagnostic tools, and current medical and surgical management options for FECD patients. These new paradigms in FECD pathogenesis present an opportunity to develop novel therapeutics for the treatment of FECD.Background Malignant mesothelioma is an aggressive cancer and has a poor prognosis. Here, we analyzed the feasibility, molecular and gender aspects of targeted therapy recommendations for malignant mesothelioma based on the individual molecular tumor profile. Methods In this single-center, real-world retrospective analysis of our platform for precision medicine, we evaluated the molecular profiling of malignant mesothelioma in 14 patients, including nine men and five women. selleck inhibitor Tumor samples of the patients were examined with a 50 gene next-generation sequencing (NGS) panel, immunohistochemistry, and fluorescence in situ hybridization, to detect possible molecular aberrations which may be targeted by off-label therapy custom-tailored to the individual patient. Results In total, we identified 11 mutations in six of the 14 patients, including BAP1, FANCA, NF1, NF2, PD-L1, RAD52D, SETD2, SRC, and TP53. No mutation was detected in eight of the 14 patients. Targeted therapy was recommended for 11 out of the 14 patients. All recommendations were mainly based on the molecular characteristics determined by immunohistochemistry. Targeted therapy recommendations were significantly more often for men than women due to gender-specific differences in PDGFRα expression. Eventually, four patients received the targeted therapy, of whom one patient subsequently achieved stable disease. Conclusions Our observations suggest that a molecular-guided treatment approach is feasible for the management of advanced malignant mesothelioma. Our analysis revealed gender specific differences in PDGFRα expression that should be further evaluated in clinical trials.The recent outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an enormous threat to global public health and economies. Human coronaviruses normally cause no or mild respiratory disease but in the past two decades, potentially fatal coronavirus infections have emerged, causing respiratory tract illnesses such as pneumonia and bronchitis. These include severe acute respiratory syndrome coronavirus (SARS-CoV), followed by the Middle East respiratory syndrome coronavirus (MERS-CoV), and recently the SARS-CoV-2 coronavirus outbreak which emerged in Wuhan, China, in December 2019. Currently, most COVID-19 patients receive traditional supportive care including breathing assistance. To halt the ongoing spread of the pandemic SARS-CoV-2 coronavirus and rescue individual patients, established drugs and new therapies are under evaluation. Since it will be some time until a safe and effective vaccine will be available, the immediate priority is to harness innate immunity to accelerate early antiviral immune responses.