Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Protein kinase CK2: a newcomer in the 'druggable kinome'

The acronym CK2 (derived from the misnomer 'casein kinase' 2) denotes one of the most pleiotropic members of the eukaryotic protein kinase superfamily, characterized by an acidic consensus sequence in which a carboxylic acid (or pre-phosphorylated) side chain at position n+3 relative to the target serine/threonine residue plays a crucial role. The latest repertoire of CK2 substrates includes approx. 300 proteins, but the analysis of available phosphopeptide databases from different sources suggests that CK2 alone may be responsible for the generation of a much larger proportion (10-20%) of the eukaryotic phosphoproteome. Although for the time being CK2 is not included among protein kinases whose inhibitors are in clinical practice or in advanced clinical trials, evidence is accumulating that elevated CK2 constitutive activity co-operates to induce a number of pathological conditions, including cancer, infectious diseases, neurodegeneration and cardiovascular pathologies. The development and usage of cell-permeant, selective inhibitors discloses a scenario whereby CK2 plays a global anti-apoptotic role, which under special circumstances may lead to untimely and pathogenic cell survival

Treatment of benign endobronchial tumors: when, how, and why. Insights, experiences, and interventional pulmonology strategies

Benign endobronchial tumors are rare clinical entities characterized by considerable variability in etiology and clinical presentation. The authors report four cases of endobronchial hamartomas treated and followed up from 2018 to 2023. Three of these cases, with identical endobronchial localization in the right lower lobe, were radically treated in flexible bronchoscopy with the only use of biopsy forceps. Another case with a different localization in the left main bronchus was treated with a laser through rigid bronchoscopy. In addition, the authors outline the main interventional pulmonological strategies for the treatment of benign tumors with endobronchial growth based on the existing literature

Alectinib rescue therapy in advanced ALK rearranged lung adenocarcinoma: a case report

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that is approved as first-line treatment in adult patients with ALK-positive non-small cell lung cancer (NSCLC) and as second-line in patients previously treated with crizotinib, and has been shown in the literature to significantly prolong progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer. The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success

Tyrosine versus serine/threonine phosphorylation by protein kinase casein kinase-2 - A study with peptide substrates derived from immunophilin Fpr3

Protein kinase casein kinase-2 (CK2) is a spontaneously active, ubiquitous, and pleiotropic enzyme that phosphorylates seryl/threonyl residues specified by multiple negatively charged side chains, the one at position n + 3 being of crucial importance (minimum consensus S/T-x-x-E/D/S(P)/T(P). Recently CK2 has been reported to catalyze phosphorylation of the yeast nucleolar immunophilin Fpr3 at a tyrosyl residue (Tyr(184)) fulfilling the consensus sequence of Ser/Thr substrates (Wilson, L.K., Dhillon, N., Thorner, J., and Martin, G.S. (1997) J. Biol. Chem. 272, 12961-12967). Here we show that, by contrast to other tyrosyl peptides fulfilling the consensus sequence for CK2, a peptide reproducing the sequence around Fpr3 Tyr(184) (DEDADIY(184)DEEDYDL) is phosphorylated by CK2, albeit with much higher K(m) (384 versus 4. 3 microM) and lower V(max) (8.4 versus 1,132 nmol.min(-1).mg(-1)) than its derivative with Tyr(184) replaced by serine. The replacement of Asp at position n + 1 with alanine and, to a lesser extent, of Ile at n - 1 with Asp are especially detrimental to tyrosine phosphorylation as compared with serine phosphorylation, which is actually stimulated by the Ile to Asp modification. In contrast the replacement of Glu at n + 3 with alanine almost suppresses serine phosphorylation but not tyrosine phosphorylation. It can be concluded that CK2 is capable to phosphorylate, under special circumstances, tyrosyl residues, which are specified by structural features partially different from those that optimize Ser/Thr phosphorylation

The Rhizosphere Bacterial Microbiota of Vitis vinifera cv. Pinot Noir in an Integrated Pest Management Vineyard

Microorganisms associated with Vitis vinifera (grapevine) can affect its growth, health and grape quality. The aim of this study was to unravel the biodiversity of the bacterial rhizosphere microbiota of grapevine in an integrated pest management vineyard located in Piedmont, Italy. Comparison between the microbial community structure in the bulk and rhizosphere soil (variable: space) were performed. Moreover, the possible shifts of the bulk and rhizosphere soil microbiota according to two phenological stages such as flowering and early fruit development (variable: time) were characterized. The grapevine microbiota was identified using metagenomics and next-generation sequencing. Biodiversity was higher in the rhizosphere than in the bulk soil, independent of the phenological stage. Actinobacteria were the dominant class with frequencies ≥ 50% in all the soil samples, followed by Proteobacteria, Gemmatimonadetes, and Bacteroidetes. While Actinobacteria and Proteobacteria are well-known as being dominant in soil, this is the first time the presence of Gemmatimonadetes has been observed in vineyard soils. Gaiella was the dominant genus of Actinobacteria in all the samples. Finally, the microbiota associated with grapevine differed from the bulk soil microbiota and these variations were independent of the phenological stage of the plant