Crosstalk between endothelial progenitor cells and HCC through periostin/CCL2/CD36 supports formation of the pro-metastatic microenvironment in HCC.

Metastasis causes most cancer-related deaths, and the role and mechanism of periostin (POSTN) in the metastasis of hepatocellular carcinoma (HCC) remain undiscovered. In this study, DEN and HTVi HCC models were performed in hepatic-specific Postn ablation and Postn knock-in mouse to reveal the role of POSTN in HCC metastasis. Furthermore, POSTN was positively correlated with circulating EPCs level and promoted EPC mobilization and tumour infiltration. POSTN also mediated the crosstalk between HCC and EPCs, which promoted metastasis ability and upregulated CD36 expression in HCC through indirect crosstalk. Chemokine arrays further revealed that hepatic-derived POSTN induced elevated CCL2 expression and secretion in EPCs, and CCL2 promoted prometastatic traits in HCC. Mechanistic studies showed that POSTN upregulated CCL2 expression in EPCs via the αvß3/ILK/NF-κB pathway. CCL2 further induced CD36 expression via the CCR2/STAT3 pathway by directly binding to the promoter region of CD36. Finally, CD36 was verified to have a prometastatic role in vitro and to be correlated with POSTN expression, metastasis and recurrence in HCC in clinical samples. Our findings revealed that crosstalk between HCC and EPCs is mediated by periostin/CCL2/CD36 signalling which promotes HCC metastasis and emphasizes a potential therapeutic strategy for preventing HCC metastasis.

The protective effect of NF-κB signaling pathway inhibitor PDTC on mice with chronic atrophic gastritis.

OBJECTIVE: To understand the protective effect of NF-κB signaling pathway inhibitor pyrrolidinedithiocarbamate (PDTC) on mice with chronic atrophic gastritis (CAG). METHODS: Helicobacter pylori (H. pylori) infection combined with high-salt diet was used to construct the CAG mouse model, and 100 or 200 mg/kg/day PDTC was intragastrically treated for 8 weeks. Then, hematoxylin and eosin (HE) and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to observe the pathology of gastric mucosa, while immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immuno sorbent assay (ELISA) and western blotting were determined to detect the expression of related molecules. RESULTS: The nuclear content of NF-κB p65 in the gastric mucosa of the CAG mice was increased accompanying by the structural disorder of the gastric mucosal epithelium, inflammatory cell infiltration, intestinal metaplasia, and increased MUC2 expression, but the symptoms were alleviated after PDTC treatment. In addition, the expressions of TNF-α, IL-1ß, IL-6 and COX2 in the gastric mucosa and serum of CAG mice were higher than those control mice, which were reduced in CAG mice treated with either 100 or 200 mg/kg PDTC. Furthermore, 100 mg/kg and 200 mg/kg PDTC treatments reduced the serum PGE2 in CAG mice with the decreased PCNA and Ki-67 expression in gastric mucosa. The therapeutic effect of 200 mg/kg PDTC was significantly better than that of 100 mg/kg PDTC. CONCLUSION: PDTC inhibited inflammation and the excessive proliferation of gastric mucosal epithelial cells, thereby exerting a potential therapeutic effect on CAG.

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation.

BACKGROUND: Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats. METHODS: Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n = 8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1ß, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot. RESULTS: In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1ß, and IL-18 expression and fibrosis indexes in the kidney of rats. CONCLUSION: AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

Exciton localization and ultralow onset ultraviolet emission in ZnO nanopencils-based heterojunction diodes.

n-GaN/i-ZnO/p-GaN double heterojunction diodes were constructed by vertically binding p-GaN wafer on the tip of ZnO nanopencil arrays grown on n-GaN/sapphire substrates. An increased quantum confinement in the tip of ZnO nanopencils has been verified by photoluminescence measurements combined with quantitative analyses. Under forward bias, a sharp ultraviolet emission at ~375 nm due to localized excitons recombination can be observed in ZnO. The electroluminescence mechanism of the studied diode is tentatively elucidated using a simplified quantum confinement model. Additionally, the improved performance of the studied diode featuring an ultralow emission onset, a good operation stability and an enhanced ultraviolet emission shows the potential of our approach. This work provides a new route for the design and development of ZnO-based excitonic optoelectronic devices.

The growth of ZnO on stainless steel foils by MOCVD and its application in light emitting devices.

Direct fabrication of semiconductor light emitting devices on metal foils is beneficial, because it brings flexibility and good heat sink in the devices. In this work, we have grown ZnO on the commercially available stainless steel foils by metal-organic chemical vapor deposition for the first time. With the increase of growth temperature, the morphology changes from a thin film structure to closely stacked columns, and eventually to nanorods. The change in the migration ability of adatoms due to the increase of growth temperature plays an important role in the evolution of morphology. The samples with nanorod morphology exhibit relatively better crystallinity and optical quality. A PEDOT: PSS/PMMA/ZnO device was fabricated based on the grown ZnO nanorods. The metal-insulator-semiconductor type device shows an uncommon symmetric I-V curve. Under reverse bias, the device emits fairly pure UV light, which comes from the near band edge emission of ZnO. The working mechanism of the devices has been discussed, and a model mainly based on the Poole-Frenkel effect is proposed to describe the charge transportation of the devices.

Synthesis of α-glycosyl thiols by stereospecific ring-opening of 1,6-anhydrosugars.

Treatment of 1,6-anhydrosugars with commercially available bis(trimethylsilyl) sulfide in the presence of trimethylsilyl triflate led to the formation of α-glycosyl thiols. All the reactions were highly stereoselective and afforded the α-glycosyl thiols in good to excellent yields. By this procedure, a variety of 1,6-anhydrosugars, differing in their sugar units, glycosidic linkages, and protecting group pattern, were converted smoothly into the corresponding α-glycosyl thiols, which could be of great utility in thioglycoside chemistry. It is noteworthy that 1,6-anhydrosugars carrying the 2-O-acyl group and 1,6-anhydrosugar-containing oligosaccharides could also be ring-opened stereospecifically under the same conditions to give rise to the corresponding 1-thiosugars in high yields. Thus, a very concise and efficient access to α-glycosyl thiols of great value was established.