Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. In addition to the previously reported cytoplasmic and membranous localization, we observed nischarin in the nuclei in melanoma patients’ tissues. NISCH expression in primary melanoma had favorable prognostic value for female patients, but, unexpectedly, high NISCH expression predicted worse prognosis for males. Gene set enrichment analysis suggested significant sex-related disparities in predicted association of NISCH with several signaling pathways, as well as with different tumor immune infiltrate composition in male and female patients. Taken together, our results imply that nischarin may have a role in melanoma progression, but that fine-tuning of the pathways it regulates is sex-dependent.

Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. In addition to the previously reported cytoplasmic and membranous localization, we observed nischarin in the nuclei in melanoma patients' tissues. NISCH expression in primary melanoma had favorable prognostic value for female patients, but, unexpectedly, high NISCH expression predicted worse prognosis for males. Gene set enrichment analysis suggested signi cant sex-related disparities in predicted association of NISCH with several signaling pathways, as well as with different tumor immune in ltrate composition in male and female patients. Taken together, our results imply that nischarin may have a role in melanoma progression, but that ne-tuning of the pathways it regulates is sex-dependent.

The search for new scaffolds of medicinal significance combined with molecular shape enhances their innovative potential and continues to attract the attention of researchers. Herein, we report the synthesis, spectroscopic characterization ( 1 H and 13 C NMR, UV−vis, IR), ESI-mass spectrometry, and single-crystal X-ray diffraction analysis of a new ring system of medicinal significance, 5,6,7,9-tetrahydro-8Hindolo[3,2-e]benzazocin-8-one, and a series of derived potential ligands (HL 1 −HL 5 ), as well as ruthenium(II), osmium(II), and copper(II) complexes (1a, 1b, and 2−5). The stability of compounds in 1% DMSO aqueous solutions has been confirmed by 1 H NMR and UV−vis spectroscopy measurements. The antiproliferative activity of HL 1 −HL 5 and 1a, 1b, and 2−5 was evaluated by in vitro cytotoxicity tests against four cancer cell lines (LS-174, HCT116, MDA-MB-361, and A549) and one non-cancer cell line (MRC-5). The lead compounds HL 5 and its copper(II) complex 5 were 15× and 17×, respectively, more cytotoxic than cisplatin against human colon cancer cell line HCT116. Annexin V-FITC apoptosis assay showed dominant apoptosis inducing potential of both compounds after prolonged treatment (48 h) in HCT116 cells. HL 5 and 5 were found to induce a concentration-and time-dependent arrest of cell cycle in colon cancer cell lines. Antiproliferative activity of 5 in 3D multicellular tumor spheroid model of cancer cells (HCT116, LS-174) superior to that of cisplatin was found. Moreover, HL 5 and 5 showed notable inhibition potency against glycogen synthase kinases (GSK-3α and GSK-3β), tyrosine-protein kinase (Src), lymphocyte-specific protein-tyrosine kinase (Lck), and cyclin-dependent kinases (Cdk2 and Cdk5) (IC 50 = 1.4−6.1 μM), suggesting their multitargeted mode of action as potential anticancer drugs.

Ortopedska hirurgija danas predstavlja veliki izazov za anesteziologe sa aspekta stanja pacijenta, tipa operacije, kao i položaja koji pacijent zauzima u toku operacije. U skladu sa trendom porasta gerijatrijske populacije, ortopedski pacijenti su najčešće stari sa brojnim komorbiditetima, ali i mladi, zdravi, najčešće traumatizovani, kod kojih postojanje udruženih povreda ima značajan uticaj na izbor tipa anestezije. Prilikom izbora tipa anestezije kod ortopedskih pacijenata neophodno je da se napravi adekvatna preoperativna procena i priprema i da se sagleda celokupno stanje pacijenta, a ne samo deo od značaja za hirurgiju. U okviru preoperativne pripreme kod ortopedskih pacijenata je najčešće neophodna kardiološka, pulmološka, ali i neurološka evaluacija, zatim nazalni skrining i dekolonizacija, preoperativna priprema kože, kontrola glikemije, kao i primena antibiotske profilakse. Ortopedska hirurgija ima najveći rizik za nastanak venskog tromboembolizma. Pravovremeno započinjanje tromboprofilakse, kao i njen nastavak posle operacije, kod ortopedskih pacijenata je od izuzetnog značaja. Za optimalnu upotrebu adekvatne tromboprofilakse postoji nekoliko objavljenih vodiča sa jasnim preporukama za dnevnu kliničku praksu. Poznavanje specifičnosti operacije, toka hirurgije, kao i položaja koji pacijent zauzima omogućava obezbeđivanje adekvatnih uslova rada uz minimalne gubitke krvi i komplikacije. Smanjenje krvarenja, kako intraoperativno tako i postoperativno, postiže se normovolemijskom hipotenzijom, bledom stazom uz pomoć poveske (touriquet), ali i primenom traneksamične kiseline, bilo sistemski ili lokalno. Kao hirurgija sa velikim postoperativnim zahtevima u analgeziji, u okviru multimodalnog pristupa se sve češće, pored perifernih nervnih blokova, u svakodnevnom radu primenjuje i periartikularno ubrizgavanje lokalnog anestetika. Poznavanje specifičnosti, ali i zahteva ortopedske operacije sa adekvatnom preoperativnom pripremom, iz-Revijalni članak

Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs’ relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case–control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs’ specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs’ mRNA levels. The case–control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects’ genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case–control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ’s effects in the PBMCs of CRC patients.