Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third frequently diagnosed cancer with high incidence and mortality rate worldwide. Our previous report has demonstrated that circCOL1A1 (hsa_circ_0044556) functions as an oncogene in CRC, and Gene Ontology (GO) analysis has also revealed the strong association between circCOL1A1 and angiogenesis. However, the mechanism of circCOL1A1 or exosomal circCOL1A1 in CRC angiogenesis remains elusive. METHODS: Purified exosomes from CRC cells were characterized by nanoparticle tracking analyzing, electron microscopy and western blot. qRT-PCR, immunohistochemistry or western blot were employed to test the expression of circCOL1A1, EIF4A3, Smad pathway and angiogenic markers. Cell proliferation of HUVECs was monitored by CCK-8 assay. The migratory and angiogenic capabilities of HUVECs were detected by wound healing and tube formation assay, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and FISH assays were used to detect the interactions among circCOL1A1, EIF4A3 and Smad2/3 mRNA. The in vitro findings were verified in xenograft model. RESULTS: CRC cell-derived exosomal circCOL1A1 promoted angiogenesis of HUVECs via recruiting EIF4A3. EIF4A3 was elevated in CRC tissues, and it stimulated angiogenesis of HUVECs through directly binding and stabilizing Smad2/3 mRNA. Moreover, exosomal circCOL1A1 promoted angiogenesis via inducing Smad2/3 signaling pathway in vitro, and it also accelerated tumor growth and angiogenesis in vivo. CONCLUSION: CRC cell-derived exosomal circCOL1A1 promoted angiogenesis via recruiting EIF4A3 and activating Smad2/3 signaling.

LINC01615 maintains cell survival in adaptation to nutrient starvation through the pentose phosphate pathway and modulates chemosensitivity in colorectal cancer.

Numerous mechanisms involved in promoting cancer cell survival under nutrient starvation have been described. Long noncoding RNAs (lncRNAs) have emerged as critical players in colorectal cancer (CRC) progression, but the role of lncRNAs in the progression of CRC under nutrient starvation has not been well clarified. Here, we identified a lncRNA, LINC01615, that was significantly upregulated in response to serum starvation. LINC01615 can contribute to the adaptation of CRC cells to serum-deprived conditions and enhance cell survival under similar conditions. LINC01615 activated the pentose phosphate pathway (PPP) under serum starvation, manifested as decreased ROS production and enhanced nucleotide and lipid synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a key rate-limiting enzyme of the PPP, and LINC01615 promoted G6PD expression by competitively binding with hnRNPA1 and facilitating G6PD pre-mRNA splicing. Moreover, we also found that serum starvation led to METTL3 degradation by inducing autophagy, which further increased the stability and level of LINC01615 in a m6A-dependent manner. LINC01615 knockdown combined with oxaliplatin achieved remarkable antitumor effects in PDO and PDX models. Collectively, our results demonstrated a novel adaptive survival mechanism permitting tumor cells to survive under limiting nutrient supplies and provided a potential therapeutic target for CRC.

Value and influencing factors of preoperative MRI evaluation for previous cesarean scar defect associated abnormal uterine bleeding in patients undergoing laparoscopic surgery. / æœ¯å‰ç£å ±æŒ¯è¯„ä»·è ¹è ”é•œæ‰‹æœ¯æ²»ç–—å‰–å®«äº§åˆ‡å£ç˜¢ç—•ç¼ºé™·ç›¸å ³å¼‚å¸¸å­å®«å‡ºè¡€çš„ä»·å€¼åŠå½±å“å› ç´ ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: As the cesarean section rate increases year by year, the treatment of previous cesarean scar defects (PCSD) poses a significant challenge. This study aims to evaluate the clinical value of preoperative magnetic resonance imaging (MRI) technology and analyze relevant influencing factors for patients with abnormal uterine bleeding (AUB) associated with cesarean scar defects who underwent laparoscopic surgery. METHODS: A retrospective cohort analysis was performed on women who underwent laparoscopic surgery for PCSD-related AUB at the Department of Gynecology, the Third Xiangya Hospital of Central South University from 2018 to 2022. A total of 57 patients who underwent laparoscopic surgery for the treatment of AUB associated with PCSD were divided into 2 groups based on their postoperative clinical cure status: The clinically-cured group (n=28, 49.1%) and the non-clinically-cured group (n=29, 50.9%). After a postoperative follow-up period of 3 months for all participants, logistic regression analysis was conducted to explore the correlation between the clinical cure rate of AUB associated with cesarean scar defects treated by laparoscopic surgery and various factors. These factors included patient age, clinical symptoms, obstetric history, history of cesarean section, basic clinical information, preoperative MRI parameters, and postoperative menstrual conditions. RESULTS: There were no significant differences in many aspects, including the patient's age at the time of previous cesarean section, number of pregnancy, time since the previous cesarean section, the uterus position assessed by preoperative T2 signal MRI, defect length, defect width, residual muscle layer thickness, adjacent uterine muscle layer thickness, and distance from the defect to the external cervical os between the 2 groups (all P>0.05). However, the time of onset of AUB symptoms (P=0.036, OR=1.019, 95% CI 1.002 to 1.038) and the depth of the defect on the preoperative MRI (P=0.010, OR=5.793, 95% CI 1.635 to 25.210) were identified as risk factors affecting the clinical cure rate. CONCLUSIONS: The time of onset of AUB symptoms and the depth of the defect on preoperative MRI are risk factors that influence the clinical cure rate of laparoscopic surgery for the treatment of AUB associated with PCSD, which could be helpful for evaluating the prognosis of disease.

The N6-methyladenosine modification of circALG1 promotes the metastasis of colorectal cancer mediated by the miR-342-5p/PGF signalling pathway.

BACKGROUND: Previous studies have shown that the N6-methyladenosine (m6A) modification enhances the binding ability of mRNAs/long noncoding RNAs (lncRNAs) to microRNAs (miRNAs), but the impact of this modification on the competitive endogenous RNA (ceRNA) function of circular RNAs (circRNAs) is unclear. METHODS: We used a human circRNA microarray to detect the expression profiles of circRNAs in 3 pairs of cancer and paracancerous tissues from patients with colorectal cancer (CRC) and 3 pairs of peripheral blood specimens from patients with CRC and healthy individuals. The circRNAs highly expressed in both peripheral blood and tumour tissues of patients with CRC, including circALG1, were screened. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of an expanded sample size was performed to detect the expression level of circALG1 in peripheral blood and tumour tissues of patients with CRC and determine its correlation with clinicopathological features, and circRNA loop-forming validation and stability assays were then conducted. Transwell assays and a nude mouse cancer metastasis model were used to study the function of circALG1 in CRC and the role of altered m6A modification levels on the regulation of circALG1 function. qRT-PCR, western blot (WB), Transwell, RNA-binding protein immunoprecipitation (RIP), RNA antisense purification (RAP), and dual-luciferase reporter gene assays were performed to analyse the ceRNA mechanism of circALG1 and the effect of the m6A modification of circALG1 on the ceRNA function of this circRNA. RESULTS: CircALG1 was highly expressed in both the peripheral blood and tumour tissues of patients with CRC and was closely associated with CRC metastasis. CircALG1 overexpression promoted the migration and invasion of CRC cells, and circALG1 silencing and reduction of the circALG1 m6A modification level inhibited CRC cell migration and invasion. In vivo experiments further confirmed the prometastatic role of circALG1 in CRC. Further mechanistic studies showed that circALG1 upregulated the expression of placental growth factor (PGF) by binding to miR-342-5p and that m6A modification enhanced the binding of circALG1 to miR-342-5p and promoted its ceRNA function. CONCLUSION: M6A modification enhances the binding ability of circALG1 to miR-342-5p to promote the ceRNA function of circALG1, and circALG1 could be a potential therapeutic target in and a prognostic marker for CRC.

The global, regional, national burden of laryngeal cancer and its attributable risk factors (1990-2019) and predictions to 2035.

OBJECTIVE: We aim to report the incidence, mortality and disability-adjusted life years (DALYs) between 1990 and 2019 and provide predictions to 2035. METHODS: We use estimates from Global Burden of Disease, Injuries and Risk Factors Study 2019 to analyse the incidence, mortality and DALYs. RESULTS: In 2019, there were more than 209,149 incidence cases, with age-standardised rates (ASRs) of 2.5. Laryngeal cancer accounted for 123,356 death cases, with ASRs of 1.5. Laryngeal cancer was also responsible for 3.26 million (3,034,634 to 3,511,354) DALYs, with ASRs of 38.8 (36.1 to 41.8). In 2019, Central Europe had the highest age-standardised incidence rate. At the national level, the highest incidence rate was observed in Mongolia. Total number and rate were significantly higher among males than females across all age groups. DALYs were attributable to Alcohol use, Smoking, Occupational exposure to sulfuric acid and asbestos. The age-standardised incidence rates in seven GBD regions and 59 countries are projected to increase between 2019 and 2035. CONCLUSIONS: Despite the current and predicted decline in age-standardised incidence globally, the absolute number of estimates continue to increase. Prevention programmes should concentrate on modifiable risk factors, especially among the males across all age groups.

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer.

Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner.

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated. METHODS: Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis. RESULTS: We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice. CONCLUSIONS: The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.

Analysis of the correlation between high iodized salt intake and the risk of thyroid nodules: a large retrospective study.

BACKGROUND: Currently, whether daily excess iodized salt intake increases the risk of thyroid nodules and even thyroid cancer remains controversial. Our research group aimed to provide a theoretical basis for the clinical guidance of daily iodized salt intake and the prevention of thyroid nodules through a retrospective analysis of the correlation between daily iodized salt intake and the risk of thyroid nodules and thyroid cancer in Hunan, China. METHODS: This study retrospectively analyzed the data of subjects who underwent a physical examination at the Health Management Center, Third Xiangya Hospital of Central South University, between January 1, 2017, and December 31, 2019. Subjects enrolled in this study underwent thyroid ultrasonography and tests to urine routines and liver and kidney function, and all subjects completed a questionnaire survey. The daily iodized salt intake of the study subjects was estimated based on spot urine methods (Tanaka). A multivariate logistic regression model was used to analyze the relationship between daily iodized salt intake and thyroid nodules and thyroid cancer. RESULTS: Among the 51,637 subjects included in this study, the prevalence of thyroid nodules was 40.25%, and the prevalence of thyroid cancer was 0.76%; among all enrolled subjects, only 3.59% had a daily iodized salt intake less than 5 g. In addition, we found that a daily intake of more than 5 g of iodized salt was not only an independent risk factor for the occurrence of thyroid nodules (odds ratio (OR): 2.08, 95% confidence interval (CI): 1.86-2.31, p < 0.001) but also an independent risk factor for the occurrence of thyroid cancer (OR: 5.81, 95% CI: 1.44-23.42, p = 0.012). A pooled analysis showed a significantly higher risk of thyroid nodules in subjects aged > 60 years with a daily iodized salt intake of more than 5 g compared to subjects aged < 60 years with a daily iodized salt intake of no more than 5 g (OR: 4.88, 95% CI: 4.29-5.54, p < 0.001); the risk of thyroid cancer was not significantly different between subjects aged > 60 years with a daily iodized salt intake of more than 5 g and those aged < 60 years with a daily iodized salt intake of no more than 5 g (OR: 2.15, 95% CI: 0.52-8.95, p = 0.281). The risk of thyroid nodules was not increased in physically active subjects with a daily iodized salt intake of more than 5 g compared to physically inactive subjects with a daily iodized salt intake of no more than 5 g (OR: 1.12, 95% CI: 0.97-1.28, p = 0.111). The same protective effect of physical activity was observed for thyroid cancer in subjects whose daily iodized salt intake exceeded 5 g. The risk of thyroid nodules was reduced for subjects with an education level of postgraduate and above, even when the daily iodized salt intake exceeded 5 g, compared to those with high school education and below and a daily iodized salt intake of no more than 5 g (OR: 0.79, 95% CI: 0.66-0.93, p = 0.005); however, a protective effect of education level on the occurrence of thyroid cancer was not observed. Independent risk factors affecting daily iodized salt intake greater than 5 g included age, triglycerides, family history of tumors, physical activity, and marital status. CONCLUSIONS: Daily intake of more than 5 g of iodized salt increased the risk of thyroid nodules and thyroid cancer, while increased physical activity and education level reduced the risk of thyroid nodules and thyroid cancer caused by iodized salt intake.

MiR-133b inhibits colorectal cancer metastasis via lncRNA-LUCAT1.

Aim: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. Metastasis is the leading cause of poor prognosis of CRC patients, warranting further study of the molecular mechanism of metastasis in CRC and identification of new therapeutic targets. MiR-133b has been proven to play an important role in tumorigenesis by directly targeting coding genes. However, whether miR-133b can regulate tumorigenesis via long noncoding RNA (lncRNA) remains unclear. Methods: We systematically analyzed the expression level and correlation of miR-133b and LUCAT1 in cancer tissues and adjacent tissues from 30 patients with CRC. The effects of miR-133b and LUCAT1 on the invasive ability of CRC cells were detected by a transwell assay. The relationship between miR-133b and LUCAT1 was investigated by cells transfection experiments, rescue experiments and luciferase reporter assays. The binding of LUCAT1 and EZH2 was detected by RNA immunoprecipitation assay. Results: MiR-133b was expressed at low levels in CRC tissues, and LUCAT1 was highly expressed, with an inverse correlation between them. LUCAT1 promoted the migration and invasion of HCT116 and SW620 cells. Overexpression of LUCAT1 attenuated the inhibition of cell migration and invasion induced by miR-133b. However, the dual luciferase assay showed that miR-133b did not directly target LUCAT1. Conclusion: MiR-133b affects CRC metastasis via the LUCAT1/EZH2 complex. MiR-133b and LUCAT1 may be potential targets for antimetastasis therapy in CRC.

Value of contrast-enhanced ultrasonography in radiofrequency ablation of secondary hyperparathyroidism.

OBJECTIVES: The purpose of the current study was to determine the performance of contrast-enhanced ultrasound (CEUS) in the assessment of radiofrequency ablation (RFA) of hyperplastic parathyroid glands due to secondary hyperparathyroidism (SHPT). METHODS: Thirty-two patients, each with ≥4 hyperplastic parathyroid glands due to SHPT, underwent RFA via hydro-dissection. CEUS was performed in each patient before and during RFA. The patients in whom the intact parathyroid hormone (iPTH) level did not decrease to 300 pg/ml were examined by CEUS. The iPTH, serum calcium, and serum phosphorus levels before and after RFA were compared. RESULTS: Ablation was achieved in all patients (131 ablated glands). The volume of the glands was 479.88 ± 549.3mm3. The pre-operative and day 1 post-operative iPTH levels were 2355 ± 1062 and 292.7 ± 306.8 pg/ml, respectively. Three nodules in three patients showed little enhancement on CEUS on post-operative day 1. The iPTH level was <300 pg/mL on post-operative day 1 in 23 patients, which indicated complete ablation; follow-up evaluations were therefore performed. The pre- and post-operative iPTH levels in the 23 patients were 2113 ± 787.2 and 106.2 ± 84.62 pg/ml, respectively (p < 0.05), and the 6- and 12-month post-operative iPTH levels were 111.1 ± 56.57 and 117.6 ± 97.08 pg/ml, respectively (p > 0.05). CONCLUSIONS: CEUS-guided RFA is effective and feasible for the treatment of ≥4 hyperplastic parathyroid glands. CEUS was shown to assist the surgeon before, during, and after RFA. CEUS on post-operative day 2, but not immediately post-operatively, was shown to accurately reflect gland perfusion.

Short-Chained Platinum Complex Catalyzed Hydrosilylation under Thermomorphic Conditions: Heterogeneous Phase Separation at Ice Temperature.

Homogeneous catalysts PtCl2[5,5'-bis-(n-ClCF2(CF2)3CH2OCH2)-2,2'-bpy] (2A) and PtCl2[5,5'-bis-(n-HCF2(CF2)3CH2OCH2)-2,2'-bpy] (2B), which contained short fluorous chains, were synthesized and used in catalysis of hydrosilylation of alkynes. In these reactions the thermomorphic mode was effectively used to recover these catalysts from the reaction mixture up to eight cycles by taking advantage of heterogeneous phase separation at ice temperature. This kind of catalysis had previously been observed in fluorous catalysts of platinum containing about 50% F-content, but in this work the percentage of F-content is decreased to only about 30%, by which we termed them as "very light fluorous". Our new type of catalyst with limited number of F-content is considered as the important discovery in the fluorous technology field as the reduced number of fluorine atoms will help to be able to comply the EPA 8-carbon rule. The metal leaching after the reaction has been examined by ICP-MS, and the testing results show the leaching of residual metal to be minimal. Additionally, comparing these results to our previous work, fluorous chain assisted selectivity has been observed when different fluorous chain lengths of the catalysts are used. It has been found that there exists fluorous chain assisted better selectivity towards ß-(E) form in the Pt-catalyzed hydrosilylation of non-symmetric terminal alkyne when the Pt catalyst contains short fluorous chain (i.e., 4 Cs). Phenyl acetylenes showed the opposite regioselectivity due to pi-pi interaction while using the same catalyst via Markovnikov's addition to form terminal vinyl silane, which is then a major product for Pt-catalyzed hydrosilylation of terminal aryl acetylene with triethylsilane. Finally, the kinetic studies indicate that the insertion of alkyne into the Pt-H bond is the rate-determining step.

Emphysema-Predominant COPD Had a Greater 5-Year Mortality and a Worse Annual Decline in Lung Function Than Airway Obstruction-Predominant COPD or Asthma at Initial Same Degree of Airflow Obstruction.

Background and Objectives: We studied whether the extent of exertional oxygen desaturation and emphysema could cause greater mortality in COPD and asthma independent of airflow obstruction. Materials and Methods: We performed a 5-year longitudinal observational study in COPD and asthma patients who matched for airflow obstruction severity. All subjects performed a 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) and followed spirometry and oxygen saturation (SpO2) during the 6MWT every 3-6 months. Overall survival was recorded. Cumulative survival curves were performed according to the Kaplan-Meier method and compared with the log-rank test. Results: The COPD group had higher emphysema scores, higher Δinspiratory capacities (ICs) and lower SpO2 during the 6MWT, which showed a greater yearly decline in FEV1 (40.6 mL) and forced vital capacity (FVC) (28 mL) than the asthma group (FEV1, 9.6 mL; FVC, 1.2 mL; p < 0.05). The emphysema-predominant COPD group had an accelerated annual decline in lung function and worse survival. The nadir SpO2 ≤ 80% and a higher emphysema score were the strong risk factors for mortality in COPD patients. Conclusions: The greater structural changes with a higher emphysema score and greater desaturation during the 6MWT in COPD may contribute to worse yearly decline in FEV1 and higher five-year mortality than in asthma patients with a similar airflow obstruction. The lowest SpO2 ≤ 80% during the 6MWT and emphysema-predominant COPD were the strong independent factors for mortality in chronic obstructive airway disease patients.

Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer.

BACKGROUND: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. METHODS: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. RESULTS: Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. CONCLUSION: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

Etiology and characteristics of patients with bronchiectasis in Taiwan: a cohort study from 2002 to 2016.

BACKGROUND: Bronchiectasis is a chronic infectious respiratory disease with diverse causes and ethnic or geographic differences. However, few large-scale studies of its etiology have been conducted in Asia. This study aimed to determine the etiology and clinical features of bronchiectasis in Taiwan. METHODS: This longitudinal cohort study investigated the etiology and clinical features of newly diagnosed non-cystic fibrosis bronchiectasis patients from January 2002 to December 2016. The clinical, functional and microbiological data of patients were retrieved from the Chang Gung Research Database, which includes seven medical facilities throughout Taiwan. The index date was the date of the first bronchiectasis diagnosis. Known diseases that were diagnosed before the index date were regarded as etiologies of bronchiectasis. RESULTS: The cohort comprised 15,729 adult patients with bronchiectasis. Idiopathic (32%) was the most common cause, followed by post-pneumonia (24%). Other causes included post-tuberculosis (12%), chronic obstructive pulmonary disease (14%), asthma (10%), gastroesophageal reflux disease (2%) and rheumatic diseases (2%). At diagnosis, 8487 patients had sputum culture. Pseudomonas aeruginosa (5.3%) was the most common bacteria, followed by non-tuberculosis mycobacteria (3.6%), Haemophilus influenzae (3.4%) and Klebsiella pneumoniae (3.1%), but 6155 (72.1%) had negative sputum cultures. Patients with post-tuberculosis had a higher sputum isolation rate of non-tuberculosis mycobacteria than P. aeruginosa. Patients with post-tuberculosis and post-pneumonia bronchiectasis had a higher frequency of chronic lung infection than other groups (p < 0.05). Clinical characteristics, such as gender, lung function, comorbidities and microbiology, were significantly different between idiopathic and known etiologies. CONCLUSIONS: Idiopathic, post-infection and tuberculosis constitute major bronchiectasis etiologies in Taiwan. Clinical characteristics and sputum microbiology were distinct among separate etiology phenotypes.

Facilitating colorectal cancer cell metastasis by targeted binding of long non-coding RNA ENSG00000231881 with miR-133b via VEGFC signaling pathway.

BACKGROUND: Colorectal cancer mainly metastasizes through the lymphatic pathways and is associated with a high mortality rate. It is one of the leading causes of cancer-related deaths. In this study, the effects of long non-coding RNA (lncRNA) ENSG00000231881 on the metastasis of colorectal cancer cells were evaluated. METHODS: The expression level of ENSG00000231881 in colorectal cancer tissues was detected with bioinformatics analysis and quantitative polymerase chain reaction (qPCR) assay. Functional colorectal cancer cell models for the overexpression and interference expression of ENSG00000231881 were established. MTT, transwell, tube formation, qPCR, and western blot assays were performed to detect changes in various cellular functions and expression levels of key factors (miR-133b and vascular endothelial growth factor C [VEGFC]) in ENSG00000231881 functional models. Dual luciferase assay was performed to verify the binding relationship between ENSG00000231881 and miR-133b. RESULTS: ENSG00000231881 expression level was substantially higher in colorectal cancer tissues than in paracancerous tissues and correlated with malignancy and prognosis. In colorectal cancer cells, ENSG00000231881 overexpression significantly promoted cell proliferation, metastasis, and tube formation in lymphatic epithelium, decreased miR-133b expression, and increased VEGFC expression. On the contrary, ENSG00000231881 interference expression showed exactly opposite results. ENSG00000231881 could bind to miR-133b and consequently affect the cell functions through the regulation of VEGFC expression via miR-133b. CONCLUSION: ENSG00000231881 binds to miR-133b via competitive endogenous RNA (ceRNA) mechanism and regulates the VEGFC signaling pathway, consequently leading to the metastasis of colorectal cancer cells. Our study provides a theoretical basis for the use of ENSG00000231881 as a therapeutic target for gene-targeted therapy in colorectal cancer.

Oxygen desaturation during the 6-min walk test as a risk for osteoporosis in non-cystic fibrosis bronchiectasis.

BACKGROUND: Osteoporosis is a common comorbidity in non-cystic fibrosis (non-CF) bronchiectasis patients. We determined whether desaturation during 6-min walk test (6MWT) can be a predictor for osteoporosis risk. METHODS: This was a retrospective cross-sectional study. Sixty-six non-CF bronchiectasis patients were enrolled. Lung function, walking distance, the lowest oxygen saturation (SpO2), the fall in SpO2 (ΔSpO2), and the distance-saturation product (DSP) were determined during the 6MWT. Desaturators (n = 45) were defined as those with ΔSpO2 > 10% or the lowest SpO2 < 88%. Bone mineral density (BMD) was determined through dual-energy X-ray absorptiometry. The severity of non-CF bronchiectasis was evaluated using high-resolution computed tomography. RESULTS: Osteoporosis was evident in more desaturators (82%) than non-desaturators (43%, p < 0.01). BMD at the level of the femoral neck was significantly lower in desaturators than in non-desaturators (- 3.6 ± 1.1 vs. - 2.4 ± 0.9, p < 0.01). BMD was correlated positively with the lowest SpO2 and negatively with ΔSpO2 and severe exacerbations. In multivariate linear regression analysis, desaturation during 6MWT was the most significant predictive factor for osteoporosis (95% confidence interval - 1.60 to - 0.26, p = 0.01). Other risk factors included old age, low body mass index and severe exacerbation. CONCLUSIONS: Exertional desaturation during the 6MWT was a significant predictive factor for osteoporosis in Asian non-CF bronchiectasis patients. The 6MWT may be useful in identifying the osteoporotic phenotype of non-CF bronchiectasis and increasing clinician awareness to promote early intervention.

Long noncoding RNA LINC01510 promotes the growth of colorectal cancer cells by modulating MET expression.

BACKGROUND: Abnormal expression of long non-coding RNA (lncRNAs) often facilitates unrestricted growth of cancer cells. Long intergenic non-protein coding RNA 1510, an enhancer lncRNA (LINC01510), a lncRNA enhancer is upregulated in colorectal cancer (CRC), and its expression might relate to MET as revealed by lncRNA microarray data. However, the potential biological role of LINC01510 and its regulatory mechanism in CRC remain unclear. Therefore, we investigated the involvement of LINC01510 in the proliferation of CRC cells. METHODS: Microarray analysis, In situ hybridization, colony formation assay, MTT assay, Western blotting, quantitative RT-PCR and flow cytometry were applied. The two-tailed Student's t test and analysis of variance or general linear model of single factor variable was used for statistical analyse. RESULTS: In the present study, we found that LINC01510 was significantly upregulated in CRC tissues and cell lines. The LINC01510 expression level were associated with the clinicopathological grade and stage. Meanwhile, gain- and loss-of-function assays demonstrated that LINC01510 overexpression increased CRC cell proliferation, and promoted cell cycle progression from the G1 phase to the S phase. Further study indicated that LINC01510 was positively correlated with the expression of MET, and its effects were most likely at the transcriptional level. CONCLUSIONS: Taken together, our findings suggested that upregulation of LINC01510 contributes to the proliferation of CRC cells, at least in part, through the regulation of MET protein. LINC01510 could be a candidate prognostic biomarker and a target for new therapies in CRC patients.

Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway.

Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear. In this study, we suggested hypothesized that nintedanib can suppress MV-augmented bleomycin-induced EMT and pulmonary fibrosis by inhibiting the Src pathway. Five days after administrating bleomycin to mimic acute lung injury (ALI), C57BL/6 mice, either wild-type or Src-deficient were exposed to low tidal volume (VT ) (6 ml/kg) or high VT (30 ml/kg) MV with room air for 5 hrs. Oral nintedanib was administered once daily in doses of 30, 60 and 100 mg/kg for 5 days before MV. Non-ventilated mice were used as control groups. Following bleomycin exposure in wild-type mice, high VT MV induced substantial increases in microvascular permeability, TGF-ß1, malondialdehyde, Masson's trichrome staining, collagen 1a1 gene expression, EMT (identified by colocalization of increased staining of α-smooth muscle actin and decreased staining of E-cadherin) and alveolar epithelial apoptosis (P < 0.05). Oral nintedanib, which simulated genetic downregulation of Src signalling using Src-deficient mice, dampened the MV-augmented profibrotic mediators, EMT profile, epithelial apoptotic cell death and pathologic fibrotic scores (P < 0.05). Our data indicate that nintedanib reduces high VT MV-augmented EMT and pulmonary fibrosis after bleomycin-induced ALI, partly by inhibiting the Src pathway.

Hypertension and non-alcoholic fatty liver disease proven by transient elastography.

AIM: The relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension is poorly understood. In the present study, we aimed to assess the relationship between essential hypertension and NAFLD, by using a new diagnostic tool, transient elastography (TE). METHODS: We enrolled 836 subjects in this study. All subjects underwent a comprehensive questionnaire survey and blood test. Each patient had undergone TE to detect the controlled attenuation parameter, which was used to and quantify liver steatosis with the help of TE. RESULTS: Participants with hypertension showed a higher prevalence of NAFLD defined by TE (P < 0.05). After adjusting for body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, triglycerides, total cholesterol, and high-density lipoprotein cholesterol, the odds ratio for NAFLD, comparing the grade 3 group (systolic blood pressure level ≥ 180 mmHg and/or diastolic blood pressure level ≥ 110 mmHg) with the normal group, was 1.476 (95% confidence interval, 1.166-2.551). A stepwise multivariate linear regression analysis (R2 = 0.084, P = 0.043) retained NAFLD, BMI, and AST as significant predictors of the systolic blood pressure levels. Additionally, stepwise multivariate linear regression analysis (R2 = 0.199, P = 0.037) retained NAFLD, controlled attenuation parameter, BMI, triglycerides, and high-density lipoprotein cholesterol as significant predictors of diastolic blood pressure levels. In addition, BMI, AST, and alanine aminotransferase were associated with systolic blood pressure levels among individuals with NAFLD; BMI, AST, and total cholesterol were associated with diastolic blood pressure levels among individuals with NAFLD. CONCLUSION: The main finding of our study is that hypertensive patients have a higher prevalence of NAFLD defined by TE, and NAFLD is independently associated with hypertension and blood pressure category.