Carbon monoxide (CO) poisoning, the most frequent type of poisoning, alters hemodynamics and creates tissue hypoxia that ultimately leads to thromboembolism. We herein describe a previously healthy ...17-year-old male patient who developed acute CO poisoning while bathing in the same room as a gas heater. He was first treated with urokinase thrombolytic therapy at a local hospital, which proved ineffective. The patient was admitted to our hospital with unstable circulation and was diagnosed with massive pulmonary embolism combined with multiple organ dysfunction syndrome. His Acute Physiology and Chronic Health Evaluation II score was 22, and his Sequential Organ Failure Assessment score was 15. We faced a difficult decision regarding whether to perform surgical embolectomy or to repeat the thrombolysis. We opted to repeat the thrombolysis with successful results. Our experience may help clinicians manage similar cases in the future.
Hepatocellular carcinoma (HCC) is a type of cancer that affects the liver and has a high mortality rate. Long non-coding RNAs (lncRNAs) dysregulation can contribute to cancer occurrence and ...progression, although the underlying molecular pathways are mostly unclear. HOXC-AS3 was found to be considerably overexpressed in HCC in this investigation. The goal of this work was to look into the involvement of HOXC-AS3 in HCC and the various molecular pathways that underpin it. Normal liver and paired HCC tissues from HCC patients were used to evaluate HOXC-AS3 expression by qRT-PCR. The role of HOXC-AS3 in HCC was assessed both in vitro and in vivo. RNA pulldown, RIP and co-IP were used to demonstrate the potential mechanism by which HOXC-AS3 regulates the progression of HCC. Using qRT-PCR, it was discovered that HOXC-AS3 was substantially expressed in HCC. In vitro and in vivo, overexpression of HOXC-AS3 aided proliferation and cell cycle progression. HOXC-AS3 interacted with CDK2 to facilitate CDK2's decreased binding to p21, resulting in enhanced CDK2 activity, which promoted the phosphorylation of Rb and the progression of HCC. HOXC-AS3 is highly expressed in HCC and can promote the progression of HCC by interacting with CDK2. Therefore, targeting HOXC-AS3 is very likely to provide a new strategy for the treatment of HCC and for improving patient prognosis.
Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation‐specific homologous ...factor (EHF), a member of the E26 transformation‐specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma‐associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor‐associated macrophages (TAMs) through the C‐C motif chemokine 2/C‐C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co‐expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF‐mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2‐TAMs to inhibit EHF‐driven CCA development.
EHF plays a crucial role in promoting cholangiocarcinoma (CCA) by activating GLI1 transcription. Additionally, EHF proficiently recruits and activates tumor‐associated macrophages via the CCL2/CCR2 axis, leading to tumor microenvironment remodeling. Furthermore, the strategic combination of GANT58 (a GLI1 inhibitor) and INCB3344 (a CCR2 inhibitor) significantly reduces EHF‐driven CCA occurrence.
Small GTP-binding proteins function as regulators of specific intercellular fundamental biological processes. In this study, a small GTP-binding protein Rab7 gene, designated as TaRab7, was ...identified and characterized from a cDNA library of wheat leaves infected with Puccinia striiformis f. sp. tritici (Pst) the wheat stripe rust pathogen. The gene was predicted to encode a protein of 206 amino acids, with a molecular mass of 23.13 KDa and an isoeletric point (pI) of 5.13. Further analysis revealed the presence of a conserved signature that is characteristic of Rab7, and phylogenetic analysis demonstrated that TaRab7 has the highest similarity to a small GTP binding protein gene (BdRab7-like) from Brachypodium distachyon. Quantitative real-time PCR assays revealed that the expression of TaRab7 was higher in the early stage of the incompatible interactions between wheat and Pst than in the compatible interaction, and the transcription level of TaRab7 was also highly induced by environmental stress stimuli. Furthermore, knocking down TaRab7 expression by virus induced gene silencing enhanced the susceptibility of wheat cv. Suwon 11 to an avirulent race CYR23. These results imply that TaRab7 plays an important role in the early stage of wheat-stripe rust fungus interaction and in stress tolerance.
Hepatocellular carcinoma (HCC) has been recognized as the third leading cause of cancer-related deaths worldwide. There is increasing evidence that the abnormal expression of autophagy-related genes ...plays an important role in the occurrence and development of HCC. Therefore, the study of autophagy-related genes can further elucidate the genetic drivers of cancer and provide valuable therapeutic targets for clinical treatment. In this study, we used 232 autophagy-related genes extracted from the Human Autophagy Database (HADb) and Molecular Signatures Database (MSigDB) to construct 1884 autophagy-related gene pairs. On this basis, we developed a prognostic model based on autophagy-related gene pairs using least absolute shrinkage and selection operator (LASSO) Cox regression to evaluate the prognosis of patients after liver cancer resection. We then used 845 liver cancer samples from three different databases to test the reliability of the risk signature through survival analysis, receiver operating characteristic (ROC) curve analysis, univariate and multivariate analysis. To further explore the underlying biological mechanisms, we conducted an enrichment analysis of autophagy-related genes. Finally, we combined the signature with independent prognostic factors to construct a nomogram. Based on the autophagy-related gene pair (ARGP) signature, we can divide patients into high- or low-risk groups. Survival analysis and ROC curve analysis verified the validity of the signature (AUC: 0.786—0.828). Multivariate Cox regression showed that the risk score can be used as an independent predictor of the clinical outcomes of liver cancer patients. Notably, this model has a more accurate predictive effect than most prognostic models for hepatocellular carcinoma. Moreover, our model is a powerful supplement to the HCC staging indicator, and a nomogram comprising both indicators can provide a better prognostic effect. Based on pairs of multiple autophagy-related genes, we proposed a prognostic model for predicting the overall survival rate of HCC patients after surgery, which is a promising prognostic indicator. This study confirms the importance of autophagy in the occurrence and development of HCC, and also provides potential biomarkers for targeted treatments.
Puccinia striiformis f. sp. tritici (Pst) is an obligate biotrophic fungus that causes the destructive wheat stripe rust disease worldwide. Due to the lack of reliable transformation and gene ...disruption method, knowledge about the function of Pst genes involved in pathogenesis is limited. Mitogen-activated protein kinase (MAPK) genes have been shown in a number of plant pathogenic fungi to play critical roles in regulating various infection processes. In the present study, we identified and characterized the first MAPK gene PsMAPK1 in Pst. Phylogenetic analysis indicated that PsMAPK1 is a YERK1 MAP kinase belonging to the Fus3/Kss1 class. Single nucleotide polymerphisms (SNPs) and insertion/deletion were detected in the coding region of PsMAPK1 among six Pst isolates. Real-time RT-PCR analyses revealed that PsMAPK1 expression was induced at early infection stages and peaked during haustorium formation. When expressed in Fusarium graminearum, PsMAPK1 partially rescued the map1 mutant in vegetative growth and pathogenicity. It also partially complemented the defects of the Magnaporthe oryzae pmk1 mutant in appressorium formation and plant infection. These results suggest that F. graminearum and M. oryzae can be used as surrogate systems for functional analysis of well-conserved Pst genes and PsMAPK1 may play a role in the regulation of plant penetration and infectious growth in Pst.
Rice (
) plants expressing the XA21 cell-surface receptor kinase are resistant to
pv.
infection. We previously demonstrated that expressing a chimeric protein containing the ELONGATION FACTOR Tu ...RECEPTOR (EFR) ectodomain and the XA21 endodomain (EFR:XA21) in rice does not confer robust resistance to
. To test if the XA21 ectodomain is required for
resistance, we produced transgenic rice lines expressing a chimeric protein consisting of the XA21 ectodomain and EFR endodomain (XA21:EFR) and inoculated these lines with
. We also tested if the XA21:EFR rice plants respond to a synthetic sulfated 21 amino acid derivative (RaxX21-sY) of the activator of XA21-mediated immunity, RaxX. We found that five independently transformed XA21:EFR rice lines displayed resistance to
as measured by lesion length analysis, and showed that five lines share characteristic markers of the XA21 defense response (generation of reactive oxygen species and defense response gene expression) after treatment with RaxX21-sY. Our results indicate that expression of the XA21:EFR chimeric receptor in rice confers resistance to
. These results suggest that the endodomain of the EFR and XA21 immune receptors are interchangeable and the XA21 ectodomain is the key determinant conferring robust resistance to
.
Background
Beckwith–Wiedemann syndrome (BWS) is an inherited disorder affecting 1 in 10,500 to 13,700 newborns worldwide. The disease is caused in a vast majority of patients by a molecular defect in ...the imprinted chromosome 11p15.5. Hereditary spherocytosis (HS) is a form of hemolytic anemia associated with a variety of mutations leading to congenital red blood cell (RBC) membrane defects. The prevalence of HS varies by geographic regions around the world, ranging from 1.2 in 100,000 in Asia to 1 in 2000 in Northern Europe.
Methods and Results
Herein, we report for the first time a rare case diagnosed with co‐existing BWS and HS. Based on the classical presentations, including macroglossia, hepatosplenomegaly, and macrosomia, the patient was first suspected with BWS. MS‐MLPA confirmed the BWS diagnosis based on hypomethylation of maternal 11p15.5 (KCNQ1OT1), but no copy number variations in chromosome 11 was detected by CNV‐seq. Nevertheless, to scrutinize molecular causes of other symptoms of the patient, including anemia, hyperbilirubinemia, and jaundice, a whole exome sequencing (WES) was performed. We identified a novel and de novo mutation in ANK1 gene (c.520delC). This frameshift mutation of ANK1 gene results in a truncated protein without important functional domains and impaired membrane stability and structure of the resultant red blood cells (RBCs), leading to a definitive diagnosis of HS.
Conclusion
The present case demonstrated that multiple genetic and epigenetic aberrations might co‐exist in the complex genetic diseases. For such kind of complicated cases, the different types of molecular tests, such as WES and MS‐MLPA, should be utilized in combination to reveal independent causal molecular events. The identifications from this study added new insights into the understanding of molecular mechanisms underlying the co‐existing HS and BWS.
We report a rare case with a novel mutation in ANK1 gene and concomitant BWS and HS diagnosed.
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