ABSTRACT
OBJECTIVE: Prognostic models proposed for cirrhotic patients' survival have not been satisfactorily investigated in the Vietnam population, especially in the medium-term period. PATIENTS AND METHODS: In this prospective study, we enrolled a total of 904 patients admitted to Hepato-Gastroenterology Center, Bach Mai Hospital from December 2019 to November 2021 and calculated their CP, MELD, MELD-Na score, IMELD, Refit MELD, and Refit MELD-Na after 2-year follow-up to compare their survival prognosis. RESULTS: The mean age of the patients was 53.8 ±10.8 years, and males constituted 91%. Compared with the surviving group, deceased patients had statistically significant lower albumin, higher INR, serum bilirubin, and creatinine levels with higher means of all prognostic scores. RefitMELD score had the highest AUC (0.768), followed by MELD (0.766), and the lowest belonged to RefitMELDNa (0.669). CONCLUSIONS: In conclusion, deceased patients had significantly higher values of Child-Pugh score and all MELD-based scores than survival. RefitMELD is the most reliable scoring system to predict 2-year mortality in patients with decompensated liver cirrhosis.
Subject(s)
Liver Cirrhosis , Sodium , Male , Humans , Adult , Middle Aged , Prognosis , Prospective Studies , Severity of Illness Index , ROC Curve , Retrospective StudiesABSTRACT
Mitochondrial dynamics and quality control have a central role in the maintenance of cellular integrity. Mitochondrial ubiquitin ligase membrane-associated RING-CH (MARCH5) regulates mitochondrial dynamics. Here, we show that mitochondrial adaptation to stress is driven by MARCH5-dependent quality control on acetylated Mfn1. Under mitochondrial stress conditions, levels of Mfn1 were elevated twofold and depletion of Mfn1 sensitized these cells to apoptotic death. Interestingly, overexpression of Mfn1 also promoted cell death in these cells, indicating that a fine tuning of Mfn1 levels is necessary for cell survival. MARCH5 binds Mfn1 and the MARCH5-dependent Mfn1 ubiquitylation was significantly elevated under mitochondrial stress conditions along with an increase in acetylated Mfn1. The acetylation-deficient K491R mutant of Mfn1 showed weak interaction with MARCH5 as well as reduced ubiquitylation. Neither was observed in the acetylation mimetic K491Q mutant. In addition, MARCH5-knockout mouse embryonic fibroblast and MARCH5(H43W)-expressing HeLa cells lacking ubiquitin ligase activity experienced rapid cell death upon mitochondrial stress. Taken together, a fine balance of Mfn1 levels is maintained by MARCH5-mediated quality control on acetylated Mfn1, which is crucial for cell survival under mitochondria stress conditions.
Subject(s)
GTP Phosphohydrolases/metabolism , Homeostasis , Membrane Proteins/metabolism , Mitochondria/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Acetylation/drug effects , Amino Acid Sequence , Animals , Antimycin A/analogs & derivatives , Antimycin A/pharmacology , Cell Death/drug effects , Cell Survival/drug effects , Cytoprotection/drug effects , GTP Phosphohydrolases/chemistry , Gene Knockout Techniques , HeLa Cells , Homeostasis/drug effects , Humans , Membrane Proteins/deficiency , Mice , Mitochondria/drug effects , Mitochondrial Membrane Transport Proteins/chemistry , Mitochondrial Proteins/deficiency , Molecular Sequence Data , Mutant Proteins/metabolism , Protein Binding/drug effects , Proteolysis/drug effects , Stress, Physiological/drug effects , Ubiquitin-Protein Ligases/deficiency , Ubiquitination/drug effectsABSTRACT
The variable region in the VP2 gene of twenty-three infectious bursal disease virus (IBDV) isolates, collected in Vietnam in 1997 and 1998, was amplified as cDNA by using the reverse transcription-polymerase chain reaction and sequenced. Analysis of amino acid substitutions and phylogenetic relationships of the deduced amino acid sequences (residues 206-350) showed that the nineteen Vietnamese vv IBDVs clustered with the European vv IBDVs, Japanese vv IBDVs and Chinese vv strains, and that the four vietnamese virulent strains were closely related to European virulent strain 52/70. These results suggest that Vietnamese vv IBDVs, European vv IBDVs, Japanese vv IBDVs and Chinese vv strains have the same origin.
Subject(s)
Birnaviridae Infections/veterinary , Infectious bursal disease virus/classification , Poultry Diseases/epidemiology , Poultry Diseases/virology , Viral Structural Proteins/chemistry , Amino Acid Sequence , Animals , Birnaviridae Infections/epidemiology , Birnaviridae Infections/virology , Chickens , Disease Outbreaks , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Vietnam/epidemiologyABSTRACT
The human genome contains thousands of genes that encode a diverse repertoire of odorant receptors (ORs). We report here on the identification and chromosomal localization of 74 OR-containing genomic clones. Using fluorescence in situ hybridization (FISH), we demonstrate a striking homology among a set of approximately 20 OR locations, illustrating a history of duplications that have distributed OR sequences across the genome. Half of the OR-containing BACs cloned from total genomic DNA and 86% of cosmids derived from chromosome 3 cross-hybridize to a subset of these locations, many to 17 of them. These paralogous regions are distributed on 13 chromosomes, and eight lie in terminal bands. By analyzing clones from an approximately 250 kb clone-walk across one of these sites (3p13), we show that the homology among these sites is extensive (>150 kb) and encompasses both OR genes and intergenic genomic sequences. The FISH signals appear significantly larger at some sites than at the native location, indicating that portions of some duplicons have undergone local amplification/attrition. More restricted duplications involving pairs of other genomic locations are detected with 12% of the OR-BACs. Only a small subset of OR locations is sufficiently diverged from the others that clones derived from them behave as single-copy FISH probes. We estimate that duplications encompassing members of the OR gene family account for >0.1% of the human genome. A comparison of FISH signals at orthologous locations in other primates indicates that a portion of this OR 'subgenome' has been in flux during the divergence of primates, possibly as a mechanism for evolving the repertoire of olfactory receptors.
Subject(s)
Genome, Human , Multigene Family/genetics , Receptors, Odorant/genetics , Animals , Chromosome Mapping , Chromosomes/genetics , Chromosomes, Human/genetics , Cloning, Molecular , Genomic Library , Humans , In Situ Hybridization, Fluorescence , Primates/geneticsABSTRACT
We have identified three new members of the olfactory receptor (OR) gene family within a large segment of DNA that is duplicated with high similarity near many human telomeres. This segment is present at 3q, 15q, and 19p in each of 45 unrelated humans sampled from various populations. Additional copies are present polymorphically at 11 other subtelomeric locations. The frequency with which the block is present at some locations varies among populations. While humans carry seven to 11 copies of the OR-containing block, it is located in chimpanzee and gorilla predominantly at a single site, which is not orthologous to any of the locations in the human genome. The observation that sequences flanking the OR-containing segment are duplicated on larger and different sets of chromosomes than the OR block itself demonstrates that the segment is part of a much larger, complex patchwork of subtelomeric duplications. The population analyses and structural results suggest the types of processes that have shaped these regions during evolution. From its sequence, one of the OR genes in this duplicated block appears to be potentially functional. Our findings raise the possibility that functional diversity in the OR family is generated in part through duplications and inter-chromosomal rearrangements of the DNA near human telomeres.
