Novel kinase 1 regulates CD8+T cells as a potential therapeutic mechanism for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.

GroupMorph: Medical Image Registration via Grouping Network with Contextual Fusion.

Pyramid-based deformation decomposition is a promising registration framework, which gradually decomposes the deformation field into multi-resolution subfields for precise registration. However, most pyramid-based methods directly produce one subfield per resolution level, which does not fully depict the spatial deformation. In this paper, we propose a novel registration model, called GroupMorph. Different from typical pyramid-based methods, we adopt the grouping-combination strategy to predict deformation field at each resolution. Specifically, we perform group-wise correlation calculation to measure the similarities of grouped features. After that, n groups of deformation subfields with different receptive fields are predicted in parallel. By composing these subfields, a deformation field with multi-receptive field ranges is formed, which can effectively identify both large and small deformations. Meanwhile, a contextual fusion module is designed to fuse the contextual features and provide the inter-group information for the field estimator of the next level. By leveraging the inter-group correspondence, the synergy among deformation subfields is enhanced. Extensive experiments on four public datasets demonstrate the effectiveness of GroupMorph. Code is available at https://github.com/TVayne/GroupMorph.

Prognostic value of mitochondrial CKMT2 in Pan-cancer and its tumor immune correlation analysis.

Mitochondrial metabolism has been shown to play a key role in immune cell survival and function, but mitochondrial creatine kinase 2 (CKMT2) has been relatively little studied about tumor immunity. We aimed to explore the prognostic value of CKMT2 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of CKMT2 in multiple cancers. CKMT2 was lowly expressed in 14 tumor tissues and highly expressed in 4 tumor tissues. Immunohistochemical assays showed overexpression of CKMT2 in colon cancer and rectal cancer. CKMT2 overexpression was positively correlated with the prognosis of lung adenocarcinoma and prostate cancer. CKMT2 overexpression is mainly enriched in the adaptive immune system and immune regulatory pathways of immunoglobulins. Seven cancers were positively correlated with low CKMT2 expression in tumor microenvironment analysis. Among the five cancers, low expression of CKMT2 resulted in better immunotherapy treatment outcomes. There was a strong correlation between CKMT2 and most immune-related genes in specific cancer types. CKMT2 plays an important role in tumorigenesis and cancer immunity and can be used as a prognostic biomarker and potential target for cancer immunotherapy.

Molecular Mechanism of Berberine in the Treatment of Calcified Aortic Valve Disease Based on AGE-RAGE Signal Pathway.

Objective: We aimed to explore the molecular mechanism of berberine in the treatment of calcified aortic valve disease through the network pharmacology-molecular docking method. Methods: The targets of berberine and calcified aortic valve disease were retrieved, the interactions between the targets were analyzed, Cytoscape software was used to build a "target-path" network, R language was used to conduct enrichment analysis of GO and KEGG pathways, and AutoDock Vina was used to verify the binding force of the target protein and small molecules. Results: 96 targets for berberine and 4293 disease targets were screened through multiple databases, and 56 targets were identified through veen analysis. The enrichment of PPI, GO, and KEGG pathways suggests that berberine may act on PIK3CD, PIK3CB, PIK3R1, MAPK14, MAPK10, and other targets, and regulate the role of calcified aortic valve disease through AGE-RAGE signaling pathway, Chemokine signaling pathway, Lipid and atherosclerosis, and other pathways. The docking results showed that berberine has good binding activity with the target on the key pathway AGE-RAGE signaling pathway. Conclusion: The network pharmacology preliminarily revealed the mechanism of berberine in the treatment of calcified aortic valve disease by regulating vascular calcification, inflammatory reaction, oxidative stress, and other effects, providing the basis for follow-up experimental research, and also providing the basis for clinical medication.

Sclerosing Epithelioid Fibrosarcoma of the Thoracic Vertebrae: An Fairly Unusual Case Report With a Short Review of Literature.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare subtype of soft tissue tumors, and SEF originating from the side of the spine is even rarer. We report that a 28-year-old young woman suffered from chest pain and back pain for 3 years, and thereafter she went to see a doctor because her condition deteriorated. Enhanced CT showed that the right posterior upper chest wall mass invaded the adjacent bone, and the boundary between the lesion and the surrounding tissues was relatively clear. She then underwent posterior tumor removal surgery. The pathological examination confirmed the diagnosis of SEF. In histomorphology, the tumor displayed a typical epithelioid clear cell morphology, accompanied by extensive vitrification and fibrosis, which better helped to differentiate the tumor from low grade fibromyxoid sarcoma, solitary fibrous tumor and other entities. The immunohistochemical analysis showed a diffuse positive reaction to MUC4, a highly specific marker of SEF, which was detected by Immunohistochemistry (IHC), and fluorescence in-situ hybridization (FISH) confirmed that the EWSR1 gene was rearranged, while the FUS gene was not rearranged. This is the first time that we have encountered such this rare case and thus report this case with updated literature related to this tumor.

Prognostic value of ubiquitin-conjugating enzyme E2 S overexpression in hepatocellular carcinoma.

Previous study has shown that ubiquitin-conjugating enzyme E2 S (UBE2S) is highly expressed in various human cancers. In order to study the clinical value and potential function of UBE2S in hepatocellular carcinoma (HCC), three datasets from the Oncomine database and RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed. UBE2S expression was found to be significantly higher in HCC samples, which was supported with qPCR validation. Both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that UBE2S co-expressed genes were involved in cell cycle and DNA replication. Survival analysis showed a significant reduction in overall survival of patients with high UBE2S expression from both the GSE14520 cohort and TCGA Liver hepatocellular carcinoma (LIHC) cohort. Furthermore, Gene set enrichment analysis (GSEA) revealed that high UBE2S expression in HCC patients is associated with increased expression in gene sets associated with decreased survival, increased metastasis and increased recurrence. Finally, qPCR results showed that UBE2S overexpression has diagnostic value in distinguishing between HCC and non-cancerous liver tissue, as the area under the curve (AUC) was 0.8095, and overexpression of UBE2S was significantly associated with decreased overall survival and disease-free survival in HCC patients. In conclusion, UBE2S may hold prognostic value in the treatment of HCC.

Identification of a novel human estrogen receptor-α splice variant able to enhance malignant biological behaviors of breast cancer cells.

Since the early 1990s, multiple human estrogen receptor-α (hER-α) splice variants have been identified, of which the majority contain ≥1 deleted exon, and some are expressed as proteins with modified functions from the wild-type 66 kDa hER-α (ER-α66). In the present study, a novel hER-α splice variant, ER-α30, was identified and cloned from clinical breast cancer tissue. The ER-α30 sequence lacked a ligand-binding domain and a ligand-dependent transcriptional activation domain but retained the N-terminal transcriptional activation domain, the DNA-binding domain and a partial hinge domain, and possesses a unique 10-amino-acid domain. The expression of ER-α30 was associated with ER-α66-negative and progesterone receptor-negative breast cancer. The 30 kDa protein was expressed in stably transfected MDA-MB-231 cells, and the overexpression of ER-α30 in MDA-MB-231 cells enhanced malignant biological behaviors, including cellular proliferation, migration and invasion in vitro. The results of the present study indicated that ER-α30 might represent a potential biomarker for breast cancer.

Cinnamic Acid (CINN) Induces Apoptosis and Proliferation in Human Nasopharyngeal Carcinoma Cells.

BACKGROUND/AIMS: CINN is the main ingredient of the traditional Chinese medicine cinnamon. The purpose of the present study was to investigate the effects of CINN on the proliferation and apoptosis of NPC cells and to elucidate the underlying molecular mechanisms. MATERIALS AND METHODS: CNE2 human NPC cells were treated with various CINN concentrations. The effects of CINN on the proliferation and apoptosis of CNE2 NPC cells were examined using the MTT assay and flow cytometric analysis. Additionally, western blotting was performed to analyze the expression of a number of cell cycle- and apoptosis-related proteins. RESULTS: The proliferation of CNE2 cells was significantly inhibited after treatment with different CINN concentrations for various lengths of time. The inhibitory effect of CINN was concentration-and time-dependent. Flow cytometric analysis showed that 2 mmol/L CINN displayed a significant apoptosis-inducing effect. The western blot analysis results showed that KLF6, Fas-L, Bax, P53 and caspase-3 protein expression was drastically increased in the CNE2 cells after treatment with 2 mmol/L CINN, whereas Bcl-2 and cyclin D1 protein expression was markedly reduced. CONCLUSION: CINN inhibits the proliferation and induces the apoptosis of CNE2 cells. Therefore, CINN possesses a potential anti-tumor effect.

Structure-based prediction of domain-peptide binding affinity by dissecting residue interaction profile at complex interface: a case study on CAL PDZ domain.

Many important protein interactions related to cell signaling networks and post-translational modification events are mediated by the binding of a globular domain in one protein to a short peptide stretch in another. In the current study, we describe a structure-level protocol to realize the quantitative prediction of weak affinity in such interactions. This method uses the crystal structure of CAL PDZ domain complexed with a CFTR C-terminus mimic peptide as the template to construct other congeneric domain-peptide complex structure models. Subsequently, independent residue-pair interactions between the domain and peptide in constructed complexes are computed and correlated with experimentally measured affinity of 80 CAL PDZ binders by using partial least squares (PLS) and random forest (RF). We demonstrate that (a) the nonlinear RF is time-consuming but performs much well as compared to linear PLS in modeling and predicting the binding affinity of domain-peptide interactions, (b) the proposed structure-based strategy is more effective and accurate than those of traditional sequence-based methods in capturing the binding behavior and interaction information of domain with peptide, and (c) only very few residue-pairs at complex interface contribute significantly to domain-peptide binding.

Functional characterization of the copper-transporting P-type ATPase gene of Penicillium janthinellum strain GXCR.

Copper (Cu)-transporting P-type ATPase (CTPA) genes have been documented to play an important role in resistance to heavy metals. However, our understanding of roles of CTPA genes of the filamentous fungi was based only on sequence similarity prediction before. In a previous study, we isolated a Penicillum janthinellum strain GXCR of higher tolerance to Cu (200 mM). In this study, we cloned the partial cDNA of CTPA gene, named PcpA, from the strain GXCR. Sequence alignment indicated that the cloned cDNA sequence has the highest identity (94.4%) with a predictive CTPA gene of Aspergillus clavatus. The PcpA-encoded protein, termed PcpA, has classical functional domains of CTPAs, and shows differences from reported CTPAs in some specific sequence motifs and transmembrane regions. Expression of the PcpA was induced by extracellular Cu, cadmium (Cd), and silver (Ag). PcpA RNA interference (RNAi) mutants with a reduced level of PcpA mRNA were more sensitive to Cu, iron, Cd, and Ag than the wild-type (WT) strain GXCR. When grown in the presence of Cu, iron, and Cd, intracellular Cu and iron contents in the PcpA RNAi mutant were significantly (P<0.05) lower than those in the WT; However, intracellular Cd content in the mutant was significantly (P<0.05) higher than that in the WT. Taken together, it can be concluded that the PcpA functions in Cu uptake and homeostasis, iron uptake, and Cd export from the cytosol to the extracytosol.