DataSheet_1_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.xlsx

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

Image_2_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.tif

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

DataSheet_3_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.xlsx

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

DataSheet_2_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.xlsx

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

Image_1_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.tif

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

Image_3_Characterizing ligand-receptor interactions and unveiling the pro-tumorigenic role of CCL16-CCR1 axis in the microenvironment of hepatocellular carcinoma.tif

BackgroundThe heterogeneity of the tumor microenvironment significantly influences the prognosis of hepatocellular carcinoma (HCC) patients, with cell communication through ligand-receptor complexes playing a central role.MethodsWe conducted single-cell transcriptomic analysis on ten HCC tissues to identify ligand-receptor genes involved in malignant HCC cell communication using CellChat. Leveraging RNA-Seq data from the TCGA Liver Cancer (TCGA-LIHC) and Liver Cancer - RIKEN, JP (LIRI-JP) cohorts, we employed Cox regression analysis to screen for prognosis-related genes. Prognostic risk models were constructed through unsupervised clustering and differential gene expression analysis. Subsequently, a co-culture system involving tumor cells and macrophages was established. A series of experiments, including Transwell assays, immunofluorescence staining, immunoprecipitation, flow cytometry, and immunohistochemistry, were conducted to elucidate the mechanism through which HCC cells recruit macrophages via the CCL16-CCR1 axis.ResultsSingle-cell analysis unveiled significant interactions between malignant HCC cells and macrophages, identifying 76 related ligand-receptor genes. Patients were classified into three subtypes based on the expression patterns of eight prognosis-related ligand-receptor genes. The subtype with the worst prognosis exhibited reduced infiltration of T cell-related immune cells, downregulation of immune checkpoint genes, and increased M2-like tumor-associated macrophage scores. In vitro experiments confirmed the pivotal role of the CCL16-CCR1 axis in the recruitment and M2 polarization of tumor-associated macrophages. Clinical samples demonstrated a significant association between CCL16 protein expression levels and advanced stage, lymph node metastasis, and distant metastasis. Immunohistochemistry and immunofluorescence staining further confirmed the correlation between CCL16 and CCR1, CD68, and CD206, as well as CD68+CCR1+ macrophage infiltration.ConclusionsOur study identified molecular subtypes, a prognostic model, and immune microenvironment features based on ligand-receptor interactions in malignant HCC cell communication. Moreover, we revealed the pro-tumorigenic role of HCC cells in recruiting M2-like tumor-associated macrophages through the CCL16-CCR1 axis.</p

Data_Sheet_1_v1_Case report: Reconstruction of the left renal vein with resected autologous right renal vein interposition after excision of an inferior vena cava leiomyosarcoma.pdf

BackgroundLeiomyosarcoma of the inferior vena cava (IVC) was a rather rare disease with the characteristics of invading the adjacent viscera. Surgical resection is the only potential curative treatment, and radiation therapy and chemotherapy for leiomyosarcoma are not definite. There is few literature reporting the leiomyosarcoma of the IVC.Case presentationA previously healthy 64-year-old female was admitted to the First Affiliated Hospital of China Medical University with the complaint of right lower quadrant abdominal pain for almost three years and worsening with a radiating ache in the waist recently. Contrast-enhanced computed tomography(CT) scans revealed a large (7.8 cm*5.5 cm*5.0 cm) irregular hypodense retroperitoneal mass with heterogeneous enhancement and invasion of the IVC, and the right ureter was compressed with proximal ureteral dilatation and hydrops. Three-dimensional CT of the IVC revealed that the IVC was encircled by the tumor with moderate invasion. During the operation, the tumor was resected en bloc with the IVC (from the suprarenal to infrarenal segment), the right kidney with ureter, and the duodenum seromuscular layer. As the left renal vein was involved, it was also partly resected. IVC reconstruction was performed with the interposition of a 20 mm diameter polytetrafluoroethylene (PTFE) prosthesis, and the right renal vein was anastomosed between the left renal vein and the reconstructed IVC to guarantee the left renal vein reflux. The patient had an uneventful recovery process with normal renal function after the operation. However, follow-up CT indicated that the left renal vein was blocked two weeks after the surgery. The patient was discharged two weeks after the operation. She continues well and has no evidence of disease fourteen months after the surgery.ConclusionsWide excision of the tumor en bloc with the IVC is the main treatment for leiomyosarcoma of the IVC. IVC reconstruction with prosthetic PTFE grafts is recommended. When the left renal vein is partly resected due to involvement of the tumor, reconstruction of left renal vein should also be performed to avoid renal impairment. If the right renal vein does not show tumor involvement, the resected right renal vein can be used to reconstruct the left renal vein.</p

Additional file 1: of miR-663a inhibits tumor growth and invasion by regulating TGF-β1 in hepatocellular carcinoma

The putative miR-663a binding sites. The 841 putative miRNA sites that were predicted to binding miR-663a by miRWalk, TargetScan, PITA, DIANAmT, and miRanda programs. (XLSX 64 kb

Effect of ω-3 polyunsaturated fatty acids on liver function and inflammatory reaction in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized control trials

Introduction: Several studies have investigated the relationship between ω-3 polyunsaturated fatty acids (PUFAs) administration and liver function and inflammatory reaction in patients undergoing liver resection, but the results remain conflicting and inconclusive. Areas covered: In this meta-analysis, a relevant database search was performed to retrieve all the randomized controlled trials (RCTs) exploring the effect of ω-3 PUFAs administration in patients undergoing hepatectomy until the end of April 2018. A random effect model was used to conduct this meta-analysis with RevMan 5.3.5 software. The quality of evidence for each postoperative outcome was assessed using the GRADEpro analysis. Expert opinion: 4 RCTs including 553 patients (277 with and 276 without ω-3 PUFAs) were identified. ω-3 PUFAs significantly reduced alanine aminotransferase [Mean difference (MD): −68.82, 95% confidence interval (CI): −108.55 to – 29.08; p = 0.0007]; aspartate aminotransferase (MD: −64.92, 95% CI: −112.87 to −16.98; p = 0.008), white blood cell count (MD: −1.22, 95% CI: −2.15 to −0.29; p = 0.01) and increased the level of pre-albumin on postoperative day 3 (MD: 10.42, 95% CI: 4.84 to 15.99; p = 0.0002). The results indicate that ω-3 PUFAs administration has a positive impact on the liver function and inflammatory reaction in patients undergoing liver resection.</p

DataSheet_1_Pentapeptide Protects INS-1 Cells From hIAPP-Mediated Apoptosis by Enhancing Autophagy Through mTOR Pathway.docx

The human islet amyloid polypeptide (hIAPP), the major component of islet amyloid deposition, is one of the amyloidogenic peptides and has been associated with β cell loss and dysfunction in type 2 diabetes (T2D). Autophagy plays a central role in the clearance of hIAPP aggregates, thereby diminishing the hIAPP-induced cytotoxicity. Conversely, hIAPP has been reported to have interfering effects on the autophagy. The pentapeptide FLPNF developed in our previous study has been shown to have effects on the level of the downstream proteins of mTOR and autophagy–lysosome pathway. In the present study, the peptide FLPNF-mediated increase in autophagy flux and its underlying mechanisms, as well as its protecting effect on INS-1 cells, were investigated. Autophagy flux in INS-1 cells overexpressing hIAPP (hIAPP-INS-1 cells) markedly increased after exposure to peptide FLPNF for 24 h and peaked at a concentration of 200 µM. Peptide FLPNF enhanced the autophagy by inhibiting the mTORC1 activity. Flow cytometry results showed the peptide FLPNF bind to mammalian target of rapamycin (mTOR), and further molecular docking analysis revealed a direct interaction between peptide FLPNF and the FRB domain of mTOR. Meanwhile, both peptide FLPNF and rapamycin significantly decreased the hIAPP-induced apoptosis, whereas 3-MA increased the apoptosis. Furthermore, peptide FLPNF reduced the hIAPP oligomer and improved the hIAPP-INS-1 cells insulin release function at high glucose concentration. Taken together, the peptide FLPNF decreased the hIAPP oligomer via upregulating autophagy by inhibiting mTORC1 activity, thus protecting the INS-1 cells from hIAPP-induced apoptosis and improving the insulin release function of INS-1 cells.</p