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Increased o2 unloading in two marine percomorph teleosts.
VEGFR-2 has recently become an eye-catching molecular target for the novel therapeutic designs against cancer for its well known role in persuading angiogenesis in tumor cells. The current study set sights on the exploration of novel potent natural compound targeting VEGFR-2 via computational ligand-based modeling and database screening followed by binding pattern analysis, reactivity site prediction and MD simulation studies. The known 53 VEGFR-2 inhibitors (with IC50 ranging from 0.7 nM to 9700 nM) were headed for development of Ligand based pharmacophore model using 3 D QSAR pharmacophore generation module of DS Client. Training set inhibitors (23 compounds) were exploited to create pharmacophore model based on their chemical features. The model was validated through 30 test set inhibitors and exploited further for screening of 62,082 natural compounds from InterBioscreen natural compound database. Screened compounds further went through Drug-Likeliness study, ADMET prediction, Binding pattern analysis, In silico prediction of reactivity sites, Biological activity spectra prediction, pan assay interference compound identification and MD simulation analysis. Out of 5 screened compounds, Compound A and Compound B exhibited highest binding energy judged against the standard drug "Sorafenib". On further conducting reactivity site prediction, BAS prediction, and pan assay interference compound identification, Compound B exhibited better result which was carried forward for MD simulation study for 50 ns. MD simulation results suggested that Compound B exhibited more stable binding to the active site of VEGFR-2 without causing any conformational changes in protein-ligand complex. Thereby, the investigation proposes Compound B to hold potent antiangiogenic potential targeting VEGFR-2. [Formula see text]Communicated by Ramaswamy H. Sarma.Indolent lymphomas have the potential to transform into more aggressive phenotypes. This phenomenon is best exemplified by the transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma into diffuse large B-cell lymphoma. However, it is less common to find multiple small cell lymphomas in the orbit, particularly mantle cell lymphoma. We present a case of an extranodal marginal zone lymphoma arising in the orbit that acquired a subclonal t(11;14) (q13;32) CCND1-IGH translocation, giving rise to a subclone of mantle cell lymphoma. The management of this tumor was targeted towards the more aggressive mantle cell subclone. The tumor exhibited an incomplete response to rituximab alone. To the best of the authors' knowledge, this represents the first such case to be described irrespective of site of origin.SMARCA4-deficient thoracic sarcoma is a rare tumor typically presenting as a mediastinal mass. The prognosis is estimated to be poor, and no effective treatment has been established. Selleck NDI-091143 We present a case of a 76-year-old man who was diagnosed with SMARCA4-deficient thoracic sarcoma. The provisional diagnosis was carcinoma of unknown primary but subsequently corrected to SMARCA4-deficient thoracic sarcoma based on the panel-based cancer gene screening and immunohistochemistry. Cytotoxic chemotherapy as the first- and second-line did not reveal enough therapeutic effects but third-line therapy using nivolumab showed marked tumor regression, which was sustained. This is the first case report of SMARCA4-deficient thoracic sarcoma showing a good response to nivolumab. Immune checkpoint inhibitor might be therapeutic candidates for this type of tumor.Listeriosis is a rare and severe foodborne infection caused by Listeria monocytogenes. It manifests as septicemia, neurolisteriosis, and maternal-fetal infection. In pregnancy, it may cause maternal fever, premature delivery, fetal loss, neonatal systemic and central nervous system infections. Maternal listeriosis is mostly reported during the 2nd and 3rd trimester of pregnancy, as sporadic cases or in the context of outbreaks. Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections. Here we review the clinical, pathophysiological, and microbiological features of maternal-neonatal listeriosis.Ocular sebaceous carcinoma is an uncommon, aggressive tumor arising from the Meibomian gland, Zeis gland, or sebaceous glands in the caruncle or eyelashes. We described a rare case of sebaceous carcinoma in situ in a 51-year-old female that was characterized by intraepithelial growth of sebaceous carcinoma cells with no invasive carcinoma in the underlying sebaceous glands. Early stromal invasion was identified that featured 2 distinctive but focally intermixed populations of sebaceous carcinoma cells and squamous carcinoma cells. The 2 populations of cells exhibited their respective distinct immunophenotype but both showed strong overexpression of p53. This case provides evidence to support the hypothesis that some ocular sebaceous carcinoma may arise from intraepithelial pluripotent stem cells.Background Timely recognition of patients with acute coronary syndromes (ACS) is important for successful treatment. Previous research has suggested that women with ACS present with different symptoms compared with men. This review assessed the extent of sex differences in symptom presentation in patients with confirmed ACS. Methods and Results A systematic literature search was conducted in PubMed, Embase, and Cochrane up to June 2019. Two reviewers independently screened title-abstracts and full-texts according to predefined inclusion and exclusion criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% CI of a symptom being present were calculated using aggregated and cumulative meta-analyses as well as sex-specific pooled prevalences for each symptom. Twenty-seven studies were included. Compared with men, women with ACS had higher odds of presenting with pain between the shoulder blades (OR 2.15; 95% CI, 1.95-2.37), nausea or vomiting (OR 1.64; 95% CI, 1.48-1.82) and shortness of breath (OR 1.34; 95% CI, 1.21-1.48). Women had lower odds of presenting with chest pain (OR 0.70; 95% CI, 0.63-0.78) and diaphoresis (OR 0.84; 95% CI, 0.76-0.94). Both sexes presented most often with chest pain (pooled prevalences, men 79%; 95% CI, 72-85, pooled prevalences, women 74%; 95% CI, 72-85). Other symptoms also showed substantial overlap in prevalence. The presence of sex differences has been established since the early 2000s. Newer studies did not materially change cumulative findings. Conclusions Women with ACS do have different symptoms at presentation than men with ACS, but there is also considerable overlap. Since these differences have been shown for years, symptoms should no longer be labeled as "atypical" or "typical."
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