Clinocopathologic correlation of alpha fetoprotein-expression in situ with serum levels in a large cohort of patients with hepatocellular carcinoma

Differential cysteine depletion in respiratory chain complexes enables the distinction of longevity from aerobicity.

Mitochondrially encoded proteins in long-lived animals exhibit a characteristic anomaly on the amino acid usage level: they abstain from the use of cysteine in a lifespan-dependent fashion. Here, we have further investigated this phenomenon by analyzing respiratory chain complex subunits individually. We find that complex I cysteine depletion is the almost exclusive carrier of the cysteine-lifespan correlation, whereas complex IV cysteine depletion is uniform in all aerobic animals, unrelated to longevity, but even more pronounced than complex I cysteine depletion in the longest-lived species. In nuclear encoded subunits of the respiratory chain, we find lifespan-independent cysteine deplet…

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease.

Acute graft versus host disease (aGvHD) is an important, life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). To investigate the value of multiple simultaneous colon biopsies in improving diagnostic accuracy in patients with aGvHD, we retrospectively analyzed 157 patients after alloHSCT. The biopsies were evaluated individually using three established histological grading systems (Lerner, Sale, and Melson). The maximum, minimum, median, and mean histological aGvHD grades were calculated for each patient, and the results were correlated with the Glucksberg grade of clinical manifestation of GvHD, steroid therapy status, and outcome. We found that…

Key Enzymes in Pyrimidine Synthesis, CAD and CPS1, Predict Prognosis in Hepatocellular Carcinoma

Simple Summary Individual patients with liver cancer have a highly variable clinical course. Hence, there is an urgent need to identify new prognostic markers to determine prognosis and select specific therapies. Expression of two key enzymes in pyrimidine synthesis was analyzed in a large, well-characterized cohort of patients with liver cancer. Dysregulated expression of these enzymes was associated with shorter survival of the patients. A combined score of both markers was found to be a statistically independent prognostic marker. Abstract Patients with hepatocellular carcinoma (HCC) have a highly variable clinical course. Therefore, there is an urgent need to identify new prognostic mar…

A Redox Mechanism to Explain the Avoidance of Cysteine in Long-Lived Animals

TGFβ-activated kinase 1 (TAK1) is activated and predicts prognosis in hepatocellular carcinoma

The adverse redox biochemistry of intramembrane thiols accounts for the lifespan-dependent cysteine depletion in the inner mitochondrial membrane of aerobic animals

The Differential Avoidance of Cysteine Residues in Respiratory Chain Complexes Reflects Both Longevity and Aerobicity

Cysteine, glutathione and a new genetic code: biochemical adaptations of the primordial cells that spread into open water and survived biospheric oxygenation

Abstract Life most likely developed under hyperthermic and anaerobic conditions in close vicinity to a stable geochemical source of energy. Epitomizing this conception, the first cells may have arisen in submarine hydrothermal vents in the middle of a gradient established by the hot and alkaline hydrothermal fluid and the cooler and more acidic water of the ocean. To enable their escape from this energy-providing gradient layer, the early cells must have overcome a whole series of obstacles. Beyond the loss of their energy source, the early cells had to adapt to a loss of external iron-sulfur catalysis as well as to a formidable temperature drop. The developed solutions to these two problem…

HILPDA is upregulated, predicts prognosis and promotes cancer progression in hepatocellular carcinoma

Prooxidative chain transfer activity by thiol groups in biological systems

Cysteine is arguably the best-studied biological amino acid, whose thiol group frequently participates in catalysis or ligand binding by proteins. Still, cysteine's unusual biological distribution has remained mysterious, being strikingly underrepresented in transmembrane domains and on accessible protein surfaces, particularly in aerobic life forms (“cysteine anomaly”). Noting that lipophilic thiols have been used for decades as radical chain transfer agents in polymer chemistry, we speculated that the rapid formation of thiyl radicals in hydrophobic phases might provide a rationale for the cysteine anomaly. Hence, we have investigated the effects of dodecylthiol and related compounds in i…

Epigenetic modifications precede molecular alterations and drive human hepatocarcinogenesis

Development of primary liver cancer is a multistage process. Detailed understanding of sequential epigenetic alterations is largely missing. Here, we performed Infinium Human Methylation 450k BeadChips and RNA-Seq analyses for genome-wide methylome and transcriptome profiling of cirrhotic liver (n = 7), low- (n = 4) and high-grade (n = 9) dysplastic lesions, and early (n = 5) and progressed (n = 3) hepatocellular carcinomas (HCC) synchronously detected in 8 patients with HCC with chronic hepatitis B infection. Integrative analyses of epigenetically driven molecular changes were identified and validated in 2 independent cohorts comprising 887 HCCs. Mitochondrial DNA sequencing was further em…

Diagnosis and grading of acute graft-versus-host disease in endoscopic biopsy series throughout the upper and lower intestine in patients after allogenic hematopoietic stem cell transplantation: a systematic approach.

Intestinal graft-versus-host disease (GvHD) is a potentially life-threatening condition after allogenic hematological stem cell transplantation (alloHSCT). Although efforts have been made to determine the best sites for endoscopic biopsies, an approach involving all accessible anatomical regions is lacking. We investigated 22 complete biopsy series, each comprising biopsies from 10 different sites of the upper and lower intestine from 21 patients. The majority of biopsies investigated revealed histological signs of acute GvHD. The highest incidence and most advanced grades of acute GvHD were found in the right colon and terminal ileum. We detected significant correlations between crypt or g…

Lipid droplets and associated proteins in viral hepatitis

Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data

Background: Syndecan-1 (CD138