ABSTRACT
OBJECTIVE: To develop and validate a nomogram for predicting 6-week mortality in patients with liver cirrhosis and acute upper gastrointestinal bleeding (UGIB) and to compare it with other commonly used scoring systems. METHODS: This retrospective study included cirrhotic patients with acute UGIB hospitalized between January 2013 and December 2020. Random sampling was used to divide patients into the training (n = 676) and validation cohorts (n = 291) at a 7:3 ratio. Multivariate logistic stepwise regression was used to establish a model for predicting 6-week mortality. Multiple indicators were used to validate the nomogram, including the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). RESULTS: In the training cohort, total bilirubin (TBIL) (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.22-2.50), hemoglobin (Hb) (OR 0.97, 95% CI 0.95-0.99), C-reactive protein (OR 2.79, 95% CI 1.30-6.07), prothrombin time (OR 1.17, 95% CI 1.05-1.30), and hepatic encephalopathy (stage I-II: OR 4.15, 95% CI 1.73-9.61; stage III-IV: OR 19.6, 95% CI 5.33-76.8) were identified as independent factors of 6-week mortality. The AUROC of the UGIB-LC score was 0.873 (95% CI 0.820-0.927), which was higher than that of the Child-Pugh score (0.781), model for end-stage liver disease score (0.766), and neutrophil-to-lymphocyte ratio (0.716). CONCLUSION: The UGIB-LC score is useful for predicting 6-week mortality in patients with liver cirrhosis and acute UGIB, which is superior to the other three scoring systems.
Subject(s)
End Stage Liver Disease , Nomograms , Humans , Retrospective Studies , Prognosis , Severity of Illness Index , Gastrointestinal Hemorrhage/etiology , Liver Cirrhosis/complications , Acute Disease , ROC CurveABSTRACT
Global warming is an environmental problem that cannot be ignored. High temperatures seriously affect the normal growth and development of plants, and threaten the development of agriculture and the distribution and survival of species at risk. Plants have evolved complex but efficient mechanisms for sensing and responding to high temperatures, which involve the activation of numerous functional proteins, regulatory proteins, and non-coding RNAs. These mechanisms consist of large regulatory networks that regulate protein and RNA structure and stability, induce Ca2+ and hormone signal transduction, mediate sucrose and water transport, activate antioxidant defense, and maintain other normal metabolic pathways. This article reviews recent research results on the molecular mechanisms of plant response to high temperatures, highlighting future directions or strategies for promoting plant heat tolerance, thereby helping to identify the regulatory mechanisms of heat stress responses in plants.
Subject(s)
Gene Regulatory Networks , Plant Proteins , Antioxidants/metabolism , Gene Expression Regulation, Plant , Heat-Shock Response/genetics , Hormones/metabolism , Plant Proteins/metabolism , Plants/genetics , Plants/metabolism , RNA/metabolism , Stress, Physiological/genetics , Sucrose/metabolism , Water/metabolismABSTRACT
Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of ß-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Gastric Mucosa/metabolism , Imidazoles/pharmacology , Inhibitor of Apoptosis Proteins/antagonists & inhibitors , Naphthoquinones/pharmacology , Stomach Neoplasms/pathology , Stomach Neoplasms/prevention & control , Animals , Blotting, Western , Female , Humans , Immunoenzyme Techniques , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Stomach/pathology , Stomach Neoplasms/metabolism , Survivin , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
MicroRNA (miRNA), a class of non-coding small RNAs, has been reported to be involved in a broad range of metabolic and physiological processes in plants, such as plant growth, development and responses to stresses. They participate in gene expression by degrading target genes at post-transcriptional levels. Seeds are the basic elements of plant growth and important materials for agriculture. miRNAs have been identified to be involved in seed development in many plants. Herein we review recent progresses on the miRNAs involved in seed development and their regulatory mechanisms, which will help to provide insights into further research to improve seed quality.
Subject(s)
MicroRNAs/physiology , Seeds/growth & development , Antioxidants , Cell Proliferation , Indoleacetic Acids/pharmacology , Signal Transduction/physiologyABSTRACT
High temperature has become a global concern, which seriously affects the growth and production of plants, particularly crops. Thus, the molecular mechanism of the heat stress response and breeding of heat-tolerant plants is necessary to protect food production and ensure crop safety. This review elaborates on the response networks of heat stress in plants, including the Hsf and Hsp response pathways, the response of ROS and the network of the hormones. In addition, the production of heat stress response elements during particular physiological periods of the plant is described. We also discuss the existing problems and future prospects concerning the molecular mechanisms of the heat stress response in plants.
Subject(s)
Heat-Shock Proteins/physiology , Heat-Shock Response/physiology , Plant Proteins/physiology , Plants , Heat-Shock Proteins/genetics , Heat-Shock Response/genetics , Plant Proteins/genetics , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
MicroRNAs (miRNAs) are a new class of small RNAs, which act as post-transcriptional negative regulators of gene expression. Plant miRNAs are important in the regulation of plant growth, development and in response to various abiotic and biotic stresses. miR398 is the first reported miRNA to be down-regulated by oxidative stresses. miR398 plays an impor-tant role in stresses, such as regulating copper homeostasis, in response to abiotic stresses including heavy metals, sucrose, and ozone and biotic stresses via down-regulating the expression of Cu/Zn-superoxide dismutase (CSD). This review fo-cused on the crucial role of miR398 in regulation of different stresses and the transcriptional regulation of MIR398 gene.
Subject(s)
Gene Expression Regulation, Plant , MicroRNAs/metabolism , Plant Physiological Phenomena , RNA, Plant/metabolism , MicroRNAs/genetics , Plants/genetics , Plants/metabolism , RNA, Plant/genetics , Stress, PhysiologicalABSTRACT
Essential heavy metals (e.g., copper) and non-essential metals (e.g., cadmium) are both toxic to plants at high concentrations. Recently, microRNAs (miRNAs) have emerged as important modulators of plants adaptive response to heavy metal stress. Plant miRNAs negatively regulate target mRNAs by post-transcriptional cleavage. miR398 regulates copper homeostasis via down-regulating the expression of Cu,Zn-superoxide dismutase (CSD), a scavenger of superoxide radicals. miR393 and miR171 play an important role in cadmium stress mediation. This review focuses on the recent advance in the involvement of miRNAs in copper and cadmium stress regulatory networks in plants.