Portal Hypertension Refractory Ascites Caused by Secondary Hemochromatosis.

We report a patient with refractory ascites because of portal hypertension caused by hemochromatosis secondary to osteopetrosis. To our knowledge, this is the first well-documented case of this association. A 46-year-old male patient who was repeatedly infused with red blood cells for anemia secondary to osteopetrosis suffered from refractory ascites. The serum-ascites albumin gradient was 29.9 g/L. Abdominal computed tomography (CT) showed a large amount of ascites, hepatomegaly, and splenomegaly. Bone marrow biopsy showed a small bone marrow cavity with no hematopoietic tissue. A peripheral blood smear showed tear drop red blood cells and metarubricytes. Serum ferritin was 8,855.0 ng/mL. Therefore, we considered that the ascites resulted from portal hypertension caused by hemochromatosis secondary to osteopetrosis. We simultaneously performed the transjungular intrahepatic portal-systemic shunt (TIPS) and obtained a transjungular liver biopsy. The portal pressure gradient before TIPS was 28 mmHg, and iron staining was strongly positive on liver biopsy, which confirmed our diagnosis. After TIPS, both abdominal distention and ascites gradually resolved, and no recurrence as observed after the 12-month postoperative follow-up was observed. This case indicated that regular monitoring of iron load is important for patients with osteopetrosis. TIPS is safe and effective for portal hypertension complications due to osteopetrosis.

Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p.

miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.

Expression of miR-1304 in patients with esophageal carcinoma and risk factors for recurrence.

BACKGROUND: Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis. MicroRNA (miR)-1304 is a newly discovered non-coding RNA, which shows differential expression in other cancers, and its clinical value in esophageal carcinoma remains unclear. AIM: To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical value. METHODS: The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas database. Quantitative real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of patients. The clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then analyzed. The potential target genes of miR-1304 were predicted, and then analyzed based on gene ontology, Kyoto Encyclopedia of Genes, and Genomes, and protein-protein interaction. RESULTS: The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased, and was also increased according to the database. Patients with high expression of miR-1304 suffered increased rates of tumor ≥ 3 cm, low differentiation and stage II + III. miR-1304 had a diagnostic value in identifying esophageal carcinoma, tumor size, differentiation and TNM stage. Tumor size, differentiation, TNM stage, and miR-1304 were independent risk factors for recurrence of esophageal carcinoma, and they had certain predictive and diagnostic value for the recurrence of esophageal carcinoma. Seventy-eight patients showed a 3-year survival rate of 38.46%, and patients with high expression of miR-1304 had a relatively lower survival rate. Multivariate analysis revealed that tumor size, differentiation, recurrence and miR-1304 were independent factors for the prognosis of patients. MiRTarBase, miRDB, and Targetscan predicted 20 target genes in total. Gene ontology enrichment analysis found 18 functions with a P < 0.05, and Kyoto Encyclopedia of Genes, and Genomes analysis found 11 signal pathways with a P < 0.05. String analysis of protein co-expression found 269 relationship pairs, of which co-expression with epidermal growth factor was the most common. CONCLUSION: miR-1304 can be used as a potential indicator for the diagnosis and recurrence of esophageal carcinoma and for survival of patients with this disease.

RP11-874J12.4 promotes oral squamous cell carcinoma tumorigenesis via the miR-19a-5p/EBF1 axis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) ranks as the fifth most frequent cancer worldwide, and the recurrence and migration of OSCC still pose large threats to patients. Long non-coding RNAs (lncRNAs) have recently emerged as crucial players in cancer development, and it is of great significance to understand the regulatory nexus of lncRNAs in OSCC. METHODS: Here, we identified a novel lncRNA, RP11-874J12.4, which is ectopically expressed in OSCC and facilitates OSCC. RESULTS: RP11-874J12.4 directly binds to and regulates miR-19a-5p. Interestingly, RP11-874J12.4 and miR-19a-5p form a negative regulatory loop that inhibits the expression of miR-19a-5p in OSCC. The expression of an oncogenic transcription factor, EBF1, is unleashed in OSCC due to the low expression of miR-19a-5p, which promotes the growth and migration of OSCC. CONCLUSION: Our data illustrate a regulatory axis of RP11-874J12.4/miR-19a-5P/EBF1 and an inhibitory loop with RP11-874J12.4 and miR-19a-5p. These data provide insights into the tumorigenesis of OSCC and the novel drug targets for OSCC.

Controllable growth of three-dimensional CdS nanoparticles on TiO2 nanotubes to enhance photocatalytic activity.

Exploiting photocatalysts with characteristics of low cost, high reactivity and good recyclability is a great significance for environmental remediation and energy conversion. Herein, hollow TiO2 nanotubes were fabricated by a novel and efficient method via electrospinning and an impregnation calcination method. With the hydrothermal method, the CdS nanoparticles were modified on the surface and in walls of the TiO2 nanotubes. By changing the reaction conditions, the morphology of CdS nanoparticles presents a controllable three-dimensional (3D) structure. The morphology of the samples was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The structure and components of samples were characterized by X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX) and X-ray photoelectron spectroscopy (XPS). The light absorption efficiency was detected using UV-vis diffuse reflectance spectroscopy (DRS) and photoluminescence (PL). The photocatalytic properties were evaluated by degradation of methyl orange (MO) and photocatalytic hydrogen evolution under visible light irradiation. From the results, the TiO2/CdS nanotubes exhibit better photocatalytic activity than the pure TiO2. The synthetic mechanism of TiO2/CdS heterostructures and a possible photocatalytic mechanism based on the experimental results were proposed.

Comprehensive multi-omics analysis identified core molecular processes in esophageal cancer and revealed GNGT2 as a potential prognostic marker.

BACKGROUND: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease remains elusive. AIM: To investigate comprehensively the molecular process of esophageal cancer. METHODS: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer from The Cancer Genome Atlas data. Exacting gene interaction modules were generated, and hub genes in the module interaction network were found. Further, through survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer. RESULTS: A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding, and other biological processes as well as p53 signaling pathway, epidermal growth factor signaling pathway, and epidermal growth factor receptor signaling pathway. Transcription factors (including hypoxia inducible factor 1A) and non-coding RNAs (including colorectal differentially expressed and hsa-miR-330-3p) that significantly regulate dysfunction modules were identified. Survival analysis showed that G protein subunit gamma transducin 2 (GNGT2) was closely related to survival of esophageal cancer. DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Furthermore, the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction, and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines. Moreover, cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines. CONCLUSION: This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.

Porphyromonas gingivalis-derived outer membrane vesicles promote calcification of vascular smooth muscle cells through ERK1/2-RUNX2.

The outer membrane vesicle (OMV) derived from Porphyromonas gingivalis plays an essential role in causing inflammation which, in turn, plays an important part in the pathogenesis of cardiovascular diseases such as atherosclerosis and thromboembolism. However, the contribution of oral bacteria to vascular calcification is yet to be determined. Here, we evaluated the effect of OMV on vascular smooth muscle cell (VSMC) calcification both in vitro and ex vivo. We established a reproducible P. gingivalis OMV-induced differentiation and calcification model of VSMCs in vitro. The results indicate that OMV promotes VSMC calcification in a concentration-dependent manner, modulating the expression of bone markers and SMC markers both on genes and proteins that are important for osteoblastic differentiation and mineralization of VSMCs. We also showed that the key osteogenic transcription factor, runt-related transcription factor 2 (Runx2), which is affected by upstream extracellular-regulated kinase (ERK) signaling, is a key regulator of OMV-induced VSMC differentiation and calcification. Taken together, our research demonstrates that Runx2 is a crucial component of OMV-induced calcification of VSMCs, and ERK signaling plays a vital role in mediating Runx2 up-regulation and VSMC calcification.

[Imbalance of immunological functions of Treg and TGF-ß1 aggravated cerebral ischemia damage in mice].

AIM: To investigate the changes of proportion of CD4(+);CD25(+); regulatory T cells (Treg) in Splenocytes and concentration of serum TGF-ß1 in diverse period after transient middle cerebral artery occlusion(tMCAO) in mice and correlation between Treg and TGF-ß1, so as to elucidate their roles in the immunological injury of acute ischemic stroke. METHODS: 60 male Kunming mice were randomly divided into six groups, i.e. sham group (24 h, n=10) and five tMCAO groups(ischemia/reperfusion 12 h, 24 h, 48 h, 72 h and 5 d, n=10/group), amount to six groups. The models of tMCAO were established by modified monofilament method; Neurologic deficit score was performed at each time point after tMCAO, and then, to sacrifice mice and measure the volume of cerebral infarction by TTC staining; the expression of Foxp3 in spleen was observed by frozen section and immunofluorescence method; the proportions of Treg in splenocytes were analyzed by flow cytometry(FCM) and the concentrations of serum TGF-ß1 were measured by ELISA. RESULTS: This study observed that there was obvious immunological injury and it was gradually worse. Similarly, TTC staining indicated that the volume of cerebral infarction gradually enlarged and peaked at 48 h following reperfusion, subsequently, exhibited slight decrease. Neurological function gradually improved after reperfusion. There were positive expressions of Foxp3 in the mice spleens and significant different in every groups. FCM indicated, compared with sham group, the percentage of Treg was decrease at 24 h after ischemia/reperfusion (P<0.05), and recovered normal level at 72 h, and significantly increased at 5 d (P<0.05). The level of serum TGF-ß1 also showed the similar tendency, the concentration of serum TGF-ß1 was lower at 24 h after ischemia/reperfusion than sham group, and recovered to sham's level at 48 h, and was significantly higher at 5 d than sham group (P<0.05). Otherwise, there was a positive correlation between serum level of TGF-ß1 and percentage of Treg. CONCLUSION: The levels of Treg and TGF-ß 1 were decrease in the acute period after ischemia/reperfusion, and they were significant increase in the recovery progress, which closely associated with the change of the ischemia volume. Therefore, Imbalance of Treg and TGF-ß1 is very likely to play an important role in the immunological injury of acute ischemic stroke.