Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure. Methods: Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression. Results: We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2. Conclusion: Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment.
Phosphodiesterase 4 (PDE4)-dependent cAMP signaling plays a crucial role in cognitive impairment associated with Alzheimer’s disease (AD). However, whether inhibition of PDE4 subtypes or their splice variants in the prefrontal cortex positively regulates synaptic plasticity and antioxidative stress, and reverses β-amyloid 1–42 (Aβ1–42, Aβ42)-induced cognitive impairment still need to be clarified. The present study determined whether and how PDE4D knockdown by microinjection of lenti-PDE4D-miRNA into the prefrontal cortex reversed Aβ1–42-induced cognitive impairment in behavioral, neurochemical, and molecular biology assays. The results suggested that PDE4D knockdown increased time to explore the novel object and decreased latency to leave the platform in novel object recognition and step-down passive avoidance tests. Further study suggested that PDE4D knockdown decreased the number of working memory errors in the eight-arm maze test. These effects were prevented by PKA inhibitor H89. The subsequent experiment suggested that inhibition of PDE4D in the prefrontal cortex rescued the long-term potentiation (LTP) and synaptic proteins’ expression; it also increased antioxidant response by increasing superoxide dismutase (SOD) and decreasing malondialdehyde (MDA) levels. PDE4D knockdown also increased phosphorylated cAMP response element-binding protein (pCREB), brain-derived neurotrophic factor (BNDF), and anti-apoptotic proteins’ expression, i.e., the ratio of Bcl-2/Bax, and decreased caspase-3 level in the prefrontal cortex. These findings extend the previous findings and support the hypothesis that RNA interference-mediated PDE4D knockdown in the prefrontal cortex ameliorated memory loss associated with synaptic failure in an AD mouse model by its antioxidant, anti-apoptotic, and neuroprotective properties.
Photodynamic therapy (PDT) is a new minimally invasive technique for the treatment of tumors. Compared with traditional treatments such as surgery, radiotherapy and chemotherapy, PDT has the advantages of targeted killing of primary and recurrent tumor cells, less damage to surrounding normal tissue, less complications and high repetition rate. The purpose of this study was to investigate the short-term efficacy and adverse reactions of photodynamic therapy in advanced elderly patients with esophageal-gastric junction adenocarcinoma without surgical indications. A patient with advanced adenocarcinoma of esophagus and fundus was treated with photodynamic therapy under gastroscope. Intravenous drip of Cipofen (hematoporphyrin injection 150mg / 0.9% saline 250ml) for 1 hour to keep the patient away from light.48 hours after administration, photodynamic therapy was performed with "Leimai" PDT630-A photodynamic therapy apparatus, 3cm columnar optical fiber, laser treatment wavelength of 630nm, transmission efficiency of 0.70, output power of 1.4W, irradiation at the lower segment of the esophagus and cardia for 150s. The curative effect was evaluated by comparing gastroscopy before and after photodynamic therapy. Before treatment, there were proliferative lesions in the lower part of esophagus and cardia, erosion and necrosis on the surface, stricture of esophageal cavity, huge ulcer near gastric fundus, filthy moss and dam-like hyperplasia and eminence of surrounding mucosa. After treatment, the local mucosa at the entrance of cardia became white and there was no bleeding. Within four days after treatment, the symptoms of nausea and vomiting disappeared; the adverse reaction of retrosternal discomfort began to occur on the second day after operation, and the adverse reaction was not improved after photodynamic therapy. Photodynamic therapy has a significant short-term effect on advanced elderly patients with adenocarcinoma of the esophagogastric junction, which can significantly alleviate the clinical symptoms and relieve the pain of the patients. However, the adverse reactions can not be ignored. Therefore, photodynamic targeting therapy for tumor needs to be further studied. It is believed that with the continuous development of high-performance photosensitizers and new generation lasers, and the continuous progress of endoscopy and image guidance technology, photodynamic therapy will become an important adjuvant or palliative treatment for tumor prevention and treatment.
Bladder tumor is characterized by recurrent recurrence and distant metastasis, which determines the difficulty of completely curing bladder tumor. In recent years, the number of patients with bladder cancer is increasing, and the treatment of bladder cancer has become an important direction of clinical research. It is difficult to control bladder tumor by traditional therapy. Photodynamic therapy (PDT), as a new optical therapy, has gradually become the main method in clinical treatment of bladder tumor combined with transurethral resection of bladder tumor. In this paper, a patient with superficial recurrent bladder tumor was treated by photodynamic therapy combined with transurethral resection of bladder tumor. The advantages of photodynamic therapy in the treatment of bladder tumor and the selection of photosensitizer in the process of photodynamic therapy were discussed. After two recurrences, the patients chose photodynamic therapy. The tumors were resected one by one, and the wound was coagulated by roller electrode. After the drug was retained for 20 minutes, the bladder was empty. The spherical optical fiber was implanted into the bladder. The photodynamic energy was adjusted (light power 1.8 W, light time 1302 s). There was no recurrence after operation.Most bladder tumors are superficial tumors, and bladder is a cavity organ, which determines that bladder is an ideal organ for photodynamic therapy. As a targeted drug, photosensitizer is only absorbed by bladder tumor after being perfused into bladder. The photosensitizer forms reactive oxygen species through oxygen and kills tumor cells. Clinical practice has proved that PDT has its unique advantages for superficial and recurrent bladder tumors. As the first generation photosensitizer, xipofen also has selectivity in the treatment of bladder cancer.
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