Circ_0001971 regulates oral squamous cell carcinoma progression and chemosensitivity by targeting miR-194/miR-204 in vitro and in vivo.

OBJECTIVE: Circular RNAs (circRNAs) play a wide role in human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the biological functions of circ_0001971 and associated mechanisms in OSCC. MATERIALS AND METHODS: The expression of circ_0001971, miR-194, and miR-204 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation and viability were assessed using cell counting kit-8 (CCK-8) assay. Cell migration and invasion were examined using the transwell assay. Cell apoptosis was monitored by flow cytometry assay. The protein levels of proliferation marker (CyclinD1), epithelial mesenchymal-transition (EMT) markers (E-cadherin (E-cad) and N-cadherin (N-cad)) and apoptosis markers (Cleaved-caspase-3 (Cleaved-cas-3) and Cleaved-caspase-9 (Cleaved-cas-9)) were measured by Western blot. The relationship between circ_0001971 and miR-194 or miR-204 was predicted by online tool starBase and verified by the Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Tumor formation assay in nude mice was conducted to observe the role of circ_0001971 in vivo. RESULTS: The expression of circ_0001971 was significantly increased in tumor tissues and cell lines. Circ_0001971 knockdown inhibited cell proliferation, migration, and invasion but promoted cisplatin (DDP) sensitivity and cell apoptosis. It was confirmed that miR-194 and miR-204 were targets of circ_0001971, and miR-194 inhibition or miR-204 inhibition reversed the effects of circ_0001971 knockdown in OSCC cells. Moreover, circ_0001971 knockdown impeded tumorigenesis and development in vivo. CONCLUSIONS: Circ_0001971 regulates cell proliferation, migration, invasion, apoptosis, and chemosensitivity of OSCC by interacting with miR-194 and miR-204 in vitro and in vivo. We provided a theoretical basis for the action mechanism of circ_0001971 on OSCC progression and chemosensitivity.

Hepcidin protects pulmonary artery hypertension in rats by activating NF-κB/TNF-α pathway.

OBJECTIVE: The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats. RESULTS: Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-ß, TNF-α, IL-1ß, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1ß, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group. CONCLUSIONS: Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.

Nicotinamide pretreatment alleviates mitochondrial stress and protects hypoxic myocardial cells via AMPK pathway.

OBJECTIVE: The aim of this study was to explore the protective effect of nicotinamide on hypoxic cardiomyocytes and to investigate its possible mechanism. MATERIALS AND METHODS: Primary cardiomyocytes were used as study subjects. They were divided into three groups, including the blank group, control group and nicotinamide pretreatment group. Cell counting kit-8 (CCK-8) was used to detect cell viability. Lactate dehydrogenase (LDH) was used to detect cytotoxicity and flow cytometry was used to detect cell apoptosis. Polymerase Chain Reaction (PCR) and Western blot were used to measure the expressions of genes in adenosine monophosphate-activated protein kinase (AMPK) pathway. JC-1 detected the levels of mitochondrial membrane potential and reactive oxygen species (ROS). NAD was used for nicotinamide adenine dinucleotide (NAD)+, and NAD phosphate (NADP)+ levels. Adenosine triphosphate (ATP) assay was performed for the detection of intracellular energy metabolism. RESULTS: In the absence of oxygen, nicotinamide had a protective effect on primary cardiomyocytes. Meanwhile, nicotinamide could markedly inhibit the increase of caspase3 mRNA in cardiomyocyte apoptosis pathway, and suppress the expression of apoptotic proteins. Furthermore, it could significantly induce the increase of intracellular ATP and activate the AMPK pathway. The detection of mitochondria indicated that nicotinamide alleviated hypoxic cardiomyocytes. In addition, the mitochondrial membrane potential disrupted and inhibited mitochondrial oxidative stress levels. CONCLUSIONS: Nicotinamide pretreatment protects hypoxic cardiomyocytes and reduces intracellular mitochondrial stress. This protection may be related to the induction of the AMPK pathway and the increase of intracellular energy production.

Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression.

BACKGROUND: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. METHODS: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14. RESULTS: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated. CONCLUSION: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.

Biphasic effect of daidzein on cell growth of human colon cancer cells.

Colorectal cancer is one of the most common cancers in the world, poorly responding to available chemotherapeutic agents. To investigate whether natural molecules can inhibit colon cancer progression, we investigated a principle phytoestrogen found in soybean known as daidzein, and determined its effects on the human colon cancer cell line LoVo. LoVo cells were treated with 0.1, 1, 5, 10, 50 and 100 microM daidzein for 2, 3, 4 or 5 d. The results indicated that daidzein stimulated the growth of LoVo cells at 0.1 and 1 microM whereas at higher concentrations (10, 50 and 100 microM) cell growth was inhibited in a dose-dependent manner. Treatment of daidzein at 10, 50 and 100 microM resulted in cell cycle arrest at G0/G1 phase, DNA fragmentation and increases in caspase-3 activity. There were no changes in alkaline phosphatase activity (ALP), an indicator of cell differentiation, upon treatment with daidzein when compared to controls. These results indicate that daidzein has a biphasic effect on LoVo cell growth and its tumor suppressive effect is by means of cell cycle arrest and apoptosis but not through cell differentiation.

Pulmonary lymphangioleiomyomatosis in a 29-year-old woman with bilateral spontaneous pneumothorax: case report.

Pulmonary lymphangioleiomyomatosis is a rare, progressive and fatal interstitial lung disease that affects women of child-bearing age. It is characterized by the nonneoplastic proliferation of atypical smooth muscle cells around lymphatics, venules, and bronchioles. Patients with pulmonary lymphangioleiomyomatosis most commonly present with exertional dyspnea and a cough. Pneumothorax is almost always found on the initial chest radiograph. We report a case of a 29-year-old woman who presented with abrupt right chest pain and progressive dyspnea. Physical examination in the emergency department was significantly diminished breath sounds over the right lung, and a chest X-ray revealed a right-sided pneumothorax. She required a chest tube for complete lung re-expansion. On the sixth day of admission, left-sided pneumothorax occurred and another chest tube was inserted. She underwent high-resolution computed tomography of the thorax with the findings of numerous cysts evenly distributed throughout the parenchyma of both lungs. Bilateral thoracotomy with lung biopsies and pleurodesis were performed and the surgical findings confirmed the presence of multiple, small, pink-colored cystic lesions on the surfaces of both lungs. Pathological examination showed the characteristic findings of pulmonary lymphangioleiomyomatosis.

Endobronchial metastatic disease.

BACKGROUND: Endobronchial metastasis (EM) is rare. Patients with EM are in advanced stages of disease and have poor prognoses. However, some patients have had long-term survival after aggressive treatment. METHODS: We retrospectively reviewed the records of 9678 patients who had undergone bronchoscopic procedures. Forty patients were diagnosed as having EM. RESULTS: The most common site of primary tumors was the head and neck [10 nasopharyngeal carcinomas (NPC), 2 buccal cancers, 2 glossal cancers, 2 laryngeal cancers]. Clinical manifestations included cough (50%), hemoptysis (20%), dyspnea (15%), and absence of respiratory symptoms (15%). The most common findings in chest roentgenograms (CXR) were single masses (40%). The median length of survival for all patients was 12 months (range, 6 to 18 months). The median length of survival in patients whose ages were over 70 years was 1 months and in patients less than 70 years old it was 12 months (range, 7 to 19 months) (p = 0.002). In patients whose EM extent was to the main bronchus, the median length of survival was 1 month (range, 1 to 3 months) and that in those whose EM did not extend to main bronchus was 12 months (range, 11 to 21 months) (p = 0.0004). In patients whose primary tumors were due to head and neck cancer other than NPC, the survival time was 1 month (range, 1 to 11 months), and in others it was 12 months (range, 7 to 19 months) (p = 0.0008). CONCLUSION: Three factors contributed to a poor prognosis, including the patient's age being over 70 years, primary tumors due to head and neck cancer other than NPC, and extension of the endobronchial metastatic lesion to the main bronchus.

Thymic lymphoepithelioma-like carcinoma associated with thymoma in a patient with ocular myasthenia.

A 65-year-old woman with ocular myasthenia was found to have three tumours in the anterior mediastinum, revealed by magnetic resonance imaging. All three lesions were radically resected. Histologically, one was a mixed-type thymoma, one a thymic lymphoepithelioma-like carcinoma, and the third had features of both these types. This appears to be the first reported case of coexisting thymic lymphoepithelioma-like carcinoma (TLC) and thymoma associated with ocular myasthenia.

Bronchial foreign bodies in adults.

Aspiration of foreign bodies into the bronchial tree is infrequently seen in adults. We reviewed 40 such cases during an 8-year period at Chang Gung Memorial Hospital, Kaohsiung. Only six patients had underlying conditions that contributed to the aspiration of foreign bodies. A positive history of aspiration was found in 18 patients (48%). Clinical manifestations were nonspecific. Chest roentgenograms were useful in 11 of the 40 patients. Bronchoscopic findings were classified into three groups: foreign bodies in the bronchial tree without granulation tissue, foreign bodies in the bronchial tree with marked granulation tissue and foreign bodies embedded in the granulation tissue. The diagnoses and removal of foreign bodies were successful in 37 patients (92%) using grasping forceps or biopsy forceps and in one patient using basket type grasping forceps. Complications of bronchoscopy were rare and not serious. The diagnosis of occult foreign bodies is often difficult and demands a high index of suspicion. Removal of endobronchial foreign bodies is usually possible with a flexible fiberoptic bronchoscope and has a high success rate.

Wegener's granulomatosis: a case report and literature review.

Wegener's granulomatosis may present with a variety of findings and be difficult to diagnose. We report a case of 27-year-old man presenting with chronic cough and hemoptysis who was diagnosed by open lung biopsy to have Wegener's granulomatosis. Based on this case, we reviewed the clinical features, pathophysiology, diagnosis, treatment, and prognosis of Wegener's granulomatosis.

Pyopneumothorax associated with unsuspected endobronchial foreign body: a case report.

Chronic foreign body aspiration may cause a variety of complications. Nonspecific clinical presentations and chest radiographic manifestations often result in misdiagnosis or delayed diagnosis. We report an unusual complication of chronic foreign body aspiration--pyopneumothorax--in a 52-year-old patient presenting with productive cough and intermittent fever for more than 3 months. Obstructive pneumonia was highly suspected from the computed tomographic scan of the chest. Flexible fiberoptic bronchoscopy demonstrated a fish bone in the bronchial tree. The bone was successfully removed by forceps. Thoracotomy was done later to ensue adequate drainage of the pyopneumothorax. We report this case for ongoing education to increase the index of suspicion.

Acute pneumonitis after subcutaneous injections of silicone for augmentation mammaplasty.

In a period of 3 years, seven cases of acute pneumonitis have been found after patients have been subcutaneously injected with silicone for the sole purpose of augmentation mammaplasty. Adverse symptoms following these silicone injections were fever, hypoxemia, hemoptysis, and abnormal diffuse bilateral alveolar infiltrates in both lungs. Pulmonary hemorrhaging occurred, and this was substantiated by using the bronchoscope with the bronchoalveolar lavage (BAL). The alveolar macrophage obtained from the BAL contained large quantities of pleomorphic cytoplasmic particles, which in actual fact were silicone particles. They were identified as silicone by scanning electron microscopy and energy-dispersive analysis of x-rays. This evidently showed that silicone diffusion into the circulatory system and subsequent embolization of the lung. Pulmonary function studies had shown restrictive changes with increase or normal single-breath carbon monoxide diffusing capacity (Dsb). Perfusion lung scans were interpreted as showing diffuse abnormalities consisting of decreased peripheral uptake. Acute hypoxemic respiratory failure was noted in four of these patients. Silicone injections of this nature were therefore a respiratory risk and caused the inducement of pneumonitis.

Intrathoracic meningocele in association with neurofibromatosis: report of a case.

A case of intrathoracic meningocele associated with neurofibromatosis is reported. Computed tomography (CT) demonstrated that the paravertebral mass had a characteristic low attenuation coefficient compatible with liquid content. CT-myelography further confirmed the diagnosis. We recommend that though intrathoracic meningocele is rare, it should be kept in mind when making a differential diagnosis in cases where the patient has neurofibromatosis with a posterior mediastinal mass.

Changes in erythrocyte membranes in burned rabbits.

Eighteen white rabbits were subjected to a 30 per cent TBSA full thickness burn. Wound infection was found 9-13 days after injury and became severe a week or so later. ATPase activities, antioxidation ability, the proteins of erythrocyte membranes, and the Na+ contents of erythrocytes and serum were determined. The Ca++-ATPase activity was elevated during the first 17 days postburn, but showed a decline at the time of severe wound infection; the Na+,K+-ATPase activity showed peaks on postburn days 2 and 6, and then fluctuated above the preburn level. The change in Mg++-ATPase activity was similar to Na+,K+-ATPase. The erythrocyte Na+ content was increased, and the level of serum Na+ was decreased up to postburn day 6. Subsequently the erythrocyte Na+ was reduced and the serum Na+ increased up to day 17 postburn. The percentage of erythrocyte haemolysis in H2O2 was increased after the burn and became markedly so during wound infection, indicating that the antioxidation ability of burned rabbit erythrocytes was markedly impaired. During the period of wound infection, Coomassie blue-stained protein bands in SDS-polyacrylamide gel showed some changes in size and proportion in burned rabbits. For example, the second band was wider, the band 2 to band 1 ratio increased, and band 5 was smaller than before injury. These results seem to show that burn injury, especially when associated with sepsis, may affect both the structure and function of biological membranes.

Effects of Germination on NA-K-stimulated Adenosine 5'-Triphosphatase and ATP-dependent Ion Transport of Isolated Membranes from Cotyledons.

A purified membrane fraction featuring ATPase activity was isolated from cotyledon tissue of Phaseolus vulgaris at different stages of germination. The fraction is enriched in both basal and Na(+)-K(+)-stimulated ATPase and is relatively free of contamination by fragments of mitochondrial membrane and microsomes. The isolated membranes have been tentatively identified as partially purified plasma membrane.The specific activities of the basal- and cation-sensitive ATPases were high in membrane preparations from young cotyledon tissue but decreased with advancing senescence. Electron microscopy of the preparation showed that the isolated membranes were of primarily vesicular conformation. These vesicles proved to be capable of extruding Na(+) and K(+) in the presence of ATP. Moreover, the degree of ATP-dependent extrusion varied during germination in a pattern that resembled variations during the same period in the Na(+)-K(+)-stimulated ATPase of the isolated fraction. This indicates that as the level of cation-sensitive ATPase on the membrane rises or falls, there is a corresponding change in the ability of the membrane to actively translocate Na(+) and K(+).