circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

DEAD-box helicase 1 inhibited CD8+ T cell antitumor activity by inducing PD-L1 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) does not respond well to current treatments, even immune checkpoint inhibitors. PD-L1 (programmed cell death ligand 1 or CD274 molecule)-mediated immune escape of tumor cells may be a key factor affecting the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the regulatory mechanisms of PD-L1 expression and immune escape require further exploration. Here, we observed that DDX1 (DEAD-box helicase 1) was overexpressed in HCC tissues and associated with poor prognosis in patients with HCC. Additionally, DDX1 expression correlated negatively with CD8+ T cell frequency. DDX1 overexpression significantly increased interferon gamma (IFN-γ)-mediated PD-L1 expression in HCC cell lines. DDX1 overexpression decreased IFN-γ and granzyme B production in CD8+ T cells and inhibited CD8+ T cell cytotoxic function in vitro and in vivo. In conclusion, DDX1 plays an essential role in developing the immune escape microenvironment, rendering it a potential predictor of ICI therapy efficacy in HCC.

Atrazine exposure promotes cardiomyocyte pyroptosis to exacerbate cardiotoxicity by activating NF-κB pathway.

Atrazine is a ubiquitous herbicide with persistent environmental presence and accumulation in the food chain, posing potential health hazards to organisms. Increasing evidence suggests that atrazine may have detrimental effects on various organ systems, including the nervous, digestive, and immune systems. However, the specific toxicity and underlying mechanism of atrazine-induced cardiac injury remain obscure. In this study, 4-week-old male C57BL/6 mice were administered atrazine via intragastric administration at doses of 50 and 200 mg/kg for 4 and 8 weeks, respectively. Our findings showed that atrazine exposure led to cardiac fibrosis, as evidenced by elevated heart index and histopathological scores, extensive myofiber damage, and interstitial collagen deposition. Moreover, atrazine induced cardiomyocyte apoptosis, macrophage infiltration, and excessive production of inflammatory factors. Importantly, atrazine upregulated the expressions of crucial pyroptosis proteins, including NLRP3, ASC, CASPASE1, and GSDMD, via the activation of NF-κB pathway, thus promoting cardiomyocyte pyroptosis. Collectively, our findings provide novel evidence demonstrating that atrazine may exacerbate myocardial fibrosis by inducing cardiomyocyte pyroptosis, highlighting its potential role in the development of cardiac fibrosis.

Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). Methods: A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Results: Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). Conclusion: HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.

Evaluation of five lymphocyte-based scores for prediction of mortality in hepatitis B virus-associated decompensated cirrhosis.

Background: Lymphocytes are generally accepted to be a key component of the immune response, and an inadequate immune response is closely associated with disease severity and adverse outcomes in hepatitis B virus (HBV)-infected patients. The present study aimed to determine and compare the prognostic values of five lymphocyte-based scores (monocyte-to-lymphocyte ratio [MLR], mean platelet volume-to-lymphocyte ratio [MPVLR], neutrophil-to-lymphocyte ratio [NLR], red cell distribution width-to-lymphocyte ratio [RLR], and C-reactive protein-to-lymphocyte ratio [CLR]) for HBV-associated decompensated cirrhosis (HBV-DC). Methods: Data were extracted from an institutional database. The outcome was 30-day mortality. Receiver operating characteristic curve analyses were conducted, and the resulting area under the curve (AUC) values were used to evaluate the predictive capabilities of the five lymphocyte-based scores for mortality in HBC-DC relative to Model for End-Stage Liver Disease (MELD) score. Results: The study included 273 patients, and the 30-day mortality was 20.9%. Lymphocyte counts were slightly lower in non-survivors than in survivors. The prognostic values of CLR, NLR, MLR, MPVLR, and RLR for mortality in HBV-DC were different. The predictive powers of NLR and MLR were superior to those of the other three scores and similar to that of MELD score. Multivariate analyses identified NLR, MLR, and MELD score as independent prognostic predictors. Conclusion: High NLR and MLR are easily accessible and reliable indicators for predicting 30-day mortality in HBV-DC and have superior prognostic ability compared with other lymphocyte-based scores.

A novel signature incorporating lipid metabolism- and immune-related genes to predict the prognosis and immune landscape in hepatocellular carcinoma.

Background: Liver hepatocellular carcinoma (LIHC) is a highly malignant tumor with high metastasis and recurrence rates. Due to the relation between lipid metabolism and the tumor immune microenvironment is constantly being elucidated, this work is carried out to produce a new prognostic gene signature that incorporates immune profiles and lipid metabolism of LIHC patients. Methods: We used the "DEseq2" R package and the "Venn" R package to identify differentially expressed genes related to lipid metabolism (LRDGs) in LIHC. Additionally, we performed unsupervised clustering of LIHC patients based on LRDGs to identify their subgroups and immuno-infiltration and Gene Ontology (GO) enrichment analysis on the subgroups. Next, we employed multivariate, LASSO and univariate Cox regression analyses to determine variables and to create a prognostic profile on the basis of immune- and lipid metabolism-related differential genes (IRDGs and LRDGs). We separated patients into low- and high-risk groups in accordance with the best cut-off value of risk score. We conducted Decision Curve Analysis (DCA), Receiver Operating Characteristic curve analysis as a function of time as well as Survival Analysis to evaluate this signature's prognostic value. We incorporated the clinical characteristics of patients into the risk model to obtain a nomogram prognostic model. GEO14520 and ICGC-LIRI JP datasets were employed to externally confirm the accuracy and robustness of signature. The gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were applied for investigating the underlying mechanisms. Immune infiltration analysis was implemented to examine the differences in immune between both risk groups. Single-cell RNA sequencing (scRNA-SEQ) was utilized to characterize the genes that were involved in the distribution of signature and expression characteristics of different LIHC cell types. The patients' sensitivity in both risk groups to commonly used chemotherapeutic agents and semi-inhibitory concentrations (IC50) of the drugs was assessed using the GDSC database. On the basis of the differentially expressed genes (DEGs) in the two groups, the CMAP database was adopted for the prediction of potential small-molecule compounds. Small-molecule compounds were molecularly docked with prognostic markers. Lastly, we investigated the prognostic gene expression levels in normal and LIHC tissues with immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction(qRT-PCR). Results: We built and verified a prognostic signature with seven genes that incorporated immune profiles and lipid metabolism. Patients were classified as low- and high-risk groups depending on their prognostic profiles. The overall survival (OS) was markedly lower in the high-risk group as compared to low-risk group. Time-dependent ROC curves more precisely predicted patients' survival at 1, 3 and 5 years; the area under the ROC curve was 0.81 (1 year), 0.75 (3 years) and 0.77 (5 years). The DCA curves showed the value of the prognostic genes in this signature for clinical applications. We included the patients' clinical characteristics in the risk model for both multivariate and univariate Cox regression analyses, and the findings revealed that the risk model represents an independent factor that influences OS in LIHC patients. With immune analysis, GSVA and GSEA, we identified that there are remarkable differences between the two risk groups in immune pathways, lipid metabolism, tumor development, immune cell infiltration and immune microenvironment, response to immunotherapy, and sensitivity to chemotherapy. Moreover, those with higher risk scores presented greater sensitivity to the chemotherapeutic agents. Experiments in vitro further elucidated the roles of SPP1 and FLT3 in the LIHC immune microenvironment. Furthermore, four small-molecule drugs that could target LIHC were screened. In vitro qRT-PCR , IHC revealed that the SPP1,KIF18A expressions were raised in LIHC in tumor samples, whereas FLT3,SOCS2 showed the opposite trend. Conclusions: We developed and verified a new signature comprising immune- and lipid metabolism-associated markers and to assess the prognosis and the immune status of LIHC patients. This signature can be applied to survival prediction, individualized chemotherapy, and immunotherapeutic guidance for patients with liver cancer. This study also provides potential targeted therapeutics and novel ideas for the immune evasion and progression of LIHC.

Integrative analysis of disulfidptosis and immune microenvironment in hepatocellular carcinoma: a putative model and immunotherapeutic strategies.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and m metastasis that does not respond well to current therapies and has a very poor prognosis. Disulfidptosis is a novel mode of cell death that has been analyzed as a novel therapeutic target for HCC cells. Methods: This study integrated bulk ribonucleic acid (RNA) sequencing datasets, spatial transcriptomics (ST), and single-cell RNA sequencing to explore the landscape of disulfidptosis and the immune microenvironment of HCC cells. Results: We developed a novel model to predict the prognosis of patients with HCC based on disulfidptosis. The model has good stability, applicability, and prognostic and immune response prediction abilities. N-myc downregulated gene1 (NDRG1) may contribute to poor prognosis by affecting macrophage differentiation, thus allowing HCC cells to evade the immune system. Conclusion: Our study explores the disulfidptosis of HCC cells through multi-omics and establishes a new putative model that explores possible targets for HCC treatment.

DNAH7 mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors.

Background: Colorectal cancer (CRC) is a malignant tumor associated with a high mortality rate. While the advent of immune checkpoint inhibitors (ICIs) has been a gamechanger, only a small percentage of CRC patients benefit from ICIs. The pathological mechanism of CRC is not well understood, but somatic mutations, especially missense mutations, are believed to play an important role. This study examined the relationship between ICIs in colorectal cancer and missense mutations in the axonemal dynein heavy chain gene 7 (DNAH7). Methods: A clinical cohort (n=690) and the CRC data from the publicly available Cancer Genome Atlas (TCGA) were examined. Gene Set Enrichment Analysis, ESTIMATE analysis, and clinical correlation analysis were performed to explore the effects and mechanisms of DNAH7 mutation on immunotherapy in colorectal cancer. Results: The results showed that CRC patients with DNAH7 mutations can benefit more from ICIs (P<0.05). Patients with DNAH7 mutation had higher ESTIMATE scores, immune scores, and matrix scores, compared to patients without the DNAH7 mutation (P<0.001). The transport of small molecules, keratinization, asthma, autoimmune thyroid disease, allograft rejection, and other pathways were significantly enriched in DNAH7 mutated tissues (P<0.05). The top key genes associated with the DNAH7 mutation included AQP8, MS4A12, GUCA2B, and ZG16 (P<0.01). Conclusions: The current study not only demonstrated the significance of DNAH7 as a risk factor and prognostic feature in CRC, but also revealed that DNAH7 mutations might affect the clinical efficacy of ICIs by impacting the tumor immune microenvironment.

A Green and Wide-Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water.

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence.

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated ß-galactosidase (SA-ßGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1ß (IL-1ß)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-ßGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

Dairy Consumption and Associations with Nutritional Status of Chinese Children and Adolescents.

OBJECTIVE: This study aimed to describe frequency and quantity of total dairy consumption of Chinese children and adolescents and explore the associations between dairy consumption and nutrition status, including stunting, wasting, overweight, and obesity. METHODS: Participants included 28,250 children and adolescents aged 6-17 years old. A food frequency questionnaire (FFQ) including 100 kinds of food was used to collect information about frequency and quantity of dairy consumption. Determination of stunting was with a height cutoff value for age and gender, and determination for wasting, overweight, and obesity was with BMI for age and gender. RESULTS: Of the total sample, 36.1% of children aged 6-17 reported consuming dairy food more than once per day (⪖ 1/day). The average total dairy intake of all the participants was 126.7 g/day. For boys, dairy consumption had an inverse correlation with stunting and wasting after controlling for confounders. For girls, dairy consumption was negatively associated with stunting and obesity after controlling for confounders as above. CONCLUSION: Dairy consumption in Chinese children and adolescents was relatively lower than that in developed countries, and was negatively associated with stunting and wasting for boys and with stunting and obesity for girls.

The risk factors and complications of forgotten double-J stents: A single-center experience.

BACKGROUND: Postoperative urology patients may require the insertion of a ureteral stent. However, the delayed removal or change of the ureteral stent may lead to serious consequences for some patients. This study primarily aimed to examine the risk factors and complications associated with forgotten double-J stents (DJSs). METHODS: In this retrospective study, postoperative patients who underwent DJS insertion were recruited. Based on the brand of DJS, the maximal stent life (MSL) was classified into 3-month, 6-month, and 12-month groups, and a forgotten DJS was defined as the one that had yet to be removed 2 weeks past its MSL. A total of 479 patients were analyzed. The reasons for the use of DJSs use and the time and method of their insertion were recorded, and the risk factors and possible complications associated with forgotten DJSs were analyzed. RESULTS: The primary reason for DJS insertion was urolithiasis (69.7%), and insertions performed using ureterorenoscopy were the most common (413/479, 86.2%). Eighteen patients (3.8%) had forgotten DJSs, with an average overdue period of 63.17 days (18-189 days). Multivariate analysis revealed that patients older than 60 years (odds ratio [OR] = 3.626, 95% confidence interval [CI] = 1.070-12.289; p = 0.039) and DJSs exchanged using fibrocystoscopy (OR = 5.437, 95% CI = 1.060-28.256; p = 0.042) were significantly associated with forgotten DJSs. Out of the 18 patients with forgotten DJS, three (16.67%) experienced symptomatic complications, with one developing acute pyelonephritis, and the remaining two experiencing stone encrustation. CONCLUSION: Patients older than 60 years were 3.6 times more likely to have forgotten DJSs than patients aged 60 and below, and DJSs exchanged using fibrocystoscopy were 5.4 times more likely to be forgotten than those inserted using ureterorenoscopy. Greater attention with regards to tracking and recalling DJSs should be paid in high-risk patients to prevent forgotten DJSs and associated complications.

Low Long Noncoding RNA Growth Arrest-Specific Transcript 5 Expression in the Exosomes of Lung Cancer Cells Promotes Tumor Angiogenesis.

Angiogenesis plays a key role in the development and progression of lung cancer. Recent studies have found that tumor cells can stimulate angiogenesis by secreting exosomes, which contain many long noncoding RNAs (lncRNAs), some of which are important for the development of lung cancer. However, the roles and mechanisms of exosomal lncRNAs in lung cancer angiogenesis have not yet been reported. In this study, lung cancer in mice was induced by urethane; we found that growth arrest specific 5 (GAS5) was lowly expressed in the serum exosomes and lung cancer tissues of mice with lung cancer. And there was a significant positive correlation between GAS5 expression in serum exosomes and lung cancer tissues. Furthermore, GAS5 was lowly expressed in human lung cancer tissues, lung cancer cells, and cells culture supernatant exosomes. The exosomes of lung cancer cells promoted human umbilical vein endothelial cells (HUVECs) proliferation and tube formation and inhibited their apoptosis. GAS5 overexpression in lung cancer cells increased GAS5 level in cell culture supernatant exosomes. And the exosomes of lung cancer cells containing high GAS5 level inhibited HUVECs proliferation and tube formation and increased their apoptosis. In addition, we found that GAS5 competitively bound miRNA-29-3p with phosphatase and tensin homolog (PTEN), upregulating PTEN mRNA and protein expression, and inhibited level of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3K) and serine/threonine kinase 1 (AKT) phosphorylation in HUVECs. Overall, our results suggest that exosomal GAS5 could be a new therapeutic target for lung cancer which inhibits angiogenesis.

Involvement of lncR-30245 in Myocardial Infarction-Induced Cardiac Fibrosis Through Peroxisome Proliferator-Activated Receptor-γ-Mediated Connective Tissue Growth Factor Signalling Pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as important mediators of cardiac pathophysiology. The aim of the present study is to investigate the effects of lncR-30245, an lncRNA, on cardiac fibrogenesis and the underlying mechanism. METHODS: Myocardial infarction (MI) and transforming growth factor (TGF)-ß1 were used to induce fibrotic phenotypes. Cardiac fibrosis was detected by Masson's trichrome staining. Cardiac function was evaluated by echocardiography. Western blot, quantitative reverse transcription-polymerase chain reaction, and pharmacological approaches were used to investigate the role of lncR-30245 in cardiac fibrogenesis. RESULTS: Expression of lncR-30245 was significantly increased in MI hearts and TGF-ß1-treated cardiac fibroblasts (CFs). LncR-30245 was mainly located in the cytoplasm. Overexpression of lncR-30245 promoted collagen production and CF proliferation. Knockdown of lncR-30245 significantly inhibited TGF-ß1-induced collagen production and CF proliferation. LncR-30245 overexpression inhibited the antifibrotic role of peroxisome proliferator-activated receptor (PPAR)-γ and increased connective tissue growth factor (CTGF) expression, whereas lncR-30245 knockdown exerted the opposite effects. Rosiglitazone, a PPAR-γ agonist, significantly inhibited lncR-30245-induced CTGF upregulation and collagen production in CFs. In contrast, T0070907, a PPAR-γ antagonist, attenuated the inhibitory effects of lncR-30245 small interfering RNA (siRNA) on TGF-ß1-induced CTGF expression and collagen production. LncR-30245 knockdown significantly enhanced ejection fraction and fractional shortening and attenuated cardiac fibrosis in MI mice. CONCLUSION: Our study indicates that the lncR-30245/PPAR-γ/CTGF pathway mediates MI-induced cardiac fibrosis and might be a therapeutic target for various cardiac diseases associated with fibrosis.

The linc00152 Controls Cell Cycle Progression by Regulating CCND1 in 16HBE Cells Malignantly Transformed by Cigarette Smoke Extract.

Smoking is one of the major environmental risk factors for lung cancer. In recent years, the role of long-chain noncoding RNAs (lncRNAs) in chemical carcinogenesis has attracted extensive research attention. In this study, we treated human bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2 µg/ml to establish a malignantly transformed cellular model (16HBE-M). Screening of lncRNAs highly expressed in transformed cells via differential analysis revealed a crucial role of linc00152 in CSE-induced malignant transformation. The linc00152 serum level in CSE-exposed individuals was increased in a dose-dependent manner and its high expression associated with metastasis and proliferation of lung cancer tissue. In malignantly transformed 16HBE-M cells, linc00152 was involved in regulation of cell adhesion, epithelial transition and other malignant phenotypes, which in turn, affected in vivo metastasis. Interference with linc00152 expression led to G1/S arrest and inhibition of proliferation of 16HBE-M and H1299 cells. Furthermore, linc00152 promoted cyclin D1 expression and G1/S transition by functioning as an endogenous competitive RNA targeting miR-193b. Our collective findings supported a critical regulatory role of linc00152 in cell cycle alterations and abnormal proliferation in CSE-induced malignant transformation of human bronchial epithelial cells.

Spontaneous regression of adrenal metastasis from renal cell carcinoma after sunitinib withdrawal: case report and literature review.

BACKGROUND: The spontaneous regression of metastatic renal cell carcinoma is a rare phenomenon, with an estimated incidence of < 1%. We report a case of post-nephrectomy renal cell carcinoma adrenal metastasis, followed by the spontaneous regression of the metastasis after withdrawal of sunitinib. CASE PRESENTATION: The patient was a 55-year-old male with clear cell type renal cell carcinoma who previously underwent a left laparoscopic radical nephrectomy. After 51 months of follow up, a recurrence in the left renal fossa was observed and subsequently excised. Four months after excision, an abdominal Computerized tomography (CT) identified an adrenal metastasis of 1.6 cm. The patient was treated with sunitinib. However, the treatment was discontinued because of gastrointestinal side effects and fatigue. Eleven months after the discontinuation of sunitinib treatment, a progression in the adrenal metastasis growth (5.7 cm) was observed, whereas 16 months after the discontinuation, a regression of the adrenal metastasis growth (3.4 cm) was observed. During subsequent follow-ups, a gradual reduction in the size of the adrenal metastasis (1.8 cm) was observed. After 44 months from the discontinuation of sunitinib treatment, the patient was still alive and followed up in the outpatient department. CONCLUSIONS: Sunitinib is a multi-targeted inhibitor of vascular endothelial growth factor (VEGF) receptors. This compound reduces tumor angiogenesis and has been approved worldwide for the treatment of advanced renal cell carcinoma. To our knowledge, this is the fourth case of the spontaneous regression of metastatic renal cell carcinoma after the discontinuation of sunitinib treatment.

Bis-Naphthalene Cleft with Aggregation-Induced Emission Properties through Lone-Pair⋠⋠⋠π Interactions.

A rigid molecular cleft shows unique aggregation-induced emission (AIE) by restricting the motion of aldehyde through intermolecular lone pair⋅⋅⋅π interactions, which are tuned by side chains. This AIE luminogen was demonstrated to work as a fluorescent sensor for aniline and an optical chirality sensor for chiral amine.

Penile Calciphylaxis in a Patient with End-stage Renal Disease: A Case Report and Review of the Literature.

Penile calciphylaxis is a rare cause of penile gangrene that presents in patients with end-stage renal disease. The rates of comorbidity and mortality of penile calciphylaxis are extremely high. Unlike other penile gangrene, such as Fournier's gangrene, the benefit of aggressive surgical therapy is controversial. Here we present a case of penile calciphylaxis in a 43-year-old man with end-stage renal disease on hemodialysis. He received total penectomy but died due to multisystem complications 2 weeks after surgery. We review the literature on the management options and outcomes in patients with penile calciphylaxis.

RNA-binding protein trinucleotide repeat-containing 6A regulates the formation of circular RNA circ0006916, with important functions in lung cancer cells.

Circular RNAs (circRNAs) are widespread and diverse endogenous RNAs distinct from traditional linear RNAs, which may regulate gene expression in eukaryotes. However, the function of human circRNAs, including their potential role in lung cancer, remains largely unknown. We screened the circRNA circ0006916, which was evidently down-regulated in 16HBE-T cells (anti-benzopyrene-trans-7, 8-dihydrodiol-9, 10-epoxide-transformed human bronchial epithelial cells), and in A549 and H460 cell lines. Silencing of circ0006916, but not its parental gene homer scaffolding protein 1 (HOMER1), promoted cell proliferation via speeding up the cell cycle process rather than by inhibiting apoptosis; conversely, overexpression of circ0006916 had the opposite effect. Luciferase-screening assay indicated that circ0006916 bound to miR-522-3p and inhibited pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) activity. We also explored the effect of the RNA-binding protein trinucleotide repeat-containing 6A (TNRC6A) on circ0006916 production. Circ0006916 expression was decreased after silencing TNRC6A. TNRC6A bound to the intron regions around the circRNA-forming exons of circ0006916, as shown by RNA immunoprecipitation assay combined with sequencing analysis. The association of circ0006916 with TNRC6A was further verified by RNA pull-down assays. We then constructed a carrier and confirmed that TNRC6A binding to the flanked intron region of circ0006916 was necessary for generation of circ0006916. These results demonstrate that TNRC6A regulates the biogenesis of the circRNA circ0006916, which has a regulatory role in cell growth.

Preoperative treatment with 5α-reductase inhibitors and the risk of hemorrhagic events in patients undergoing transurethral resection of the prostate - A population-based cohort study.

OBJECTIVES: To assess the associations between preoperative treatment with 5-alpha reductase inhibitors and the risks of blood transfusion during transurethral resection of the prostate and blood clot evacuation or emergency department visits for hematuria within 1 month after surgery. METHODS: We used data from the Taiwan National Health Insurance Research Database in this population-based cohort study. A total of 3,126 patients who underwent first-time transurethral resection of the prostate from 2004 to 2013 were identified. Adjusted odds ratios estimated by multiple logistic regression models were used to assess the independent effects of the preoperative use of 5-alpha reductase inhibitors on the risks of perioperative hemorrhagic events after adjustment for potential confounders. RESULTS: Two hundred and ninety-seven (9.4%) patients were treated with 5-alpha reductase inhibitors for <3 months, and 65 (2.1%) patients were treated for ≥3 months prior to undergoing transurethral resection of the prostate. The blood transfusion rates for patients who were not treated with 5-alpha reductase inhibitors (controls), patients who were treated with 5-alpha reductase inhibitors for <3 months, and patients who were treated with 5-alpha reductase inhibitors ≥3 months were 9.5%, 8.8%, and 3.1%, respectively. 5-alpha reductase inhibitors tended to decrease the risk of blood transfusion; however, this association was not statistically significant (adjusted odds ratio=0.14, 95% confidence interval: 0.02-1.01). Age ≥80 years, coagulopathy, and a resected prostate tissue weight >50 g were associated with significantly higher risks of blood transfusion than other parameters. CONCLUSIONS: This nationwide study did not show that significant associations exist between 5-alpha reductase inhibitor use before transurethral resection of the prostate and the risks of blood transfusion and blood clot evacuation or emergency visits for hematuria.