Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-506 pathway.

HOXA transcript at the distal tip (HOTTIP), a lncRNA, induces cell proliferation and cancer progression. However, the expression and function of HOTTIP in renal cell carcinoma (RCC) were rarely reported. The role of the HOTTIP in RCC was explored in this study. HOTTIP expresses higher in RCC tissues than in normal tissues and indicates poor prognosis based on the TCGA database. The over- and low-expression HOTTIP cell line was established in this research to assess the oncogenic function of HOTTIP in RCC progression. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for miR-506. RIP experiment and luciferase assay were performed to explore the mechanisms of the sponge between HOTTIP and miR-506. HOTTIP down-regulation attenuated cell proliferation, migration, and invasion, which could be rescued by miR-506 down-regulation. On the whole, this study revealed that the HOTTIP/miR-506 axis has a dominant impact on RCC progression and potentially provides a novel strategy for RCC diagnosis and therapy.

Research of targeted therapy for renal cancer from 2006 to 2022: a bibliometric and visualized analysis.

Background: This review aimed to analyze the research progress and development trends in targeted therapy (TT) for renal cancer (RC) from 2006 to 2022. Methods: The Web of Science Core Collection database was searched using the search terms "renal cancer", "kidney neoplasms", "kidney cancer", and "targeted therapy", and all publications were extracted. VOSviewer version 1.6.18 was used to complete the visual analysis based on the information of publications, including author, journal, subject, year, and institution. Results: A total of 1,136 studies related to TT for RC were found. The top journals in this field were the Journal of Clinical Oncology, Annals of Oncology, and European Urology. Among them, the Journal of Clinical Oncology had the highest number of publications (n=35). In terms of country, the United States had the highest number of publications (n=366). The main document type was article, which accounted for 64.26% of the total publications. Conclusions: To the best of our knowledge, this is the first bibliometric analysis related to TT for RC. The annual number of publications has exhibited a steady growth trend, with the United States having the greatest contribution in this field. Through an analysis of a keyword time density map, we identified that hypoxia-inducing factor-1, drug resistance and therapeutic targets are the research hotspots and trends in this field.

A Novel 7-Methylguanosine (m7G)-Related Gene Signature for Overall Survival Prediction in Patient with Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common pathology type of renal cancer that has an abysmal prognosis. Although a crucial role for 7-methylguanosine modification in cancer cell development has been reported, its role in ccRCC remains uncertain. This study was conducted to determine the efficacy of predictive biomarkers based on m7G-related genes in ccRCC. Firstly, we extracted clinical data and gene expression profiles of ccRCC patients from publicly accessible databases. It identified that 22 of the m7G-related 34 genes were related to overall survival, and 5 of the 22 genes were significantly expressed differently in tumor tissues. Based on Lasso regression analysis, five optimal genes (CYFIP2, EIF4A1, NUDT1, NUDT10, and NUDT4) were chosen to build a new predictive risk model in the TCGA cohort. Validation was carried out with the E-MTAB-1980 cohort. Then, a prognostic nomogram was erected, including the m7G-related gene risk score, age, histological grade, and stage status. Further studies and analysis showed that immune cell infiltration might be associated with the m7G-related risk genes. In addition, the relationship between gene expression and drug response was evaluated by the Pearson correlation test. Therefore, the risk signature with five selected m7G-related genes may be a promising prognostic biomarker and contribute to standardized prognostic assessment for ccRCC.

Association between multiple sclerosis and prostate cancer risk: A systematic review and meta­analysis.

Prostate cancer (PCa) risk in patients with multiple sclerosis (MS) remains to be elucidated. The present study conducted a meta-analysis to assess the relationship between MS and PCa. PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to identify studies on the PCa risk in patients with MS up to September 2022. A random effects meta-analyses model was performed to estimate the relative risk (RR) and the 95% confidence intervals (CI). All eight studies involving 210,943 patients with MS were identified and included in the meta-analysis. The present study revealed that there was no significant association between MS and the risk of PCa (RR=0.78, 95% CI: 0.56-1.08, P<0.0001). Subgroup analyses verified this conclusion when stratified by regions. However, after adjusting for potential confounders, the findings suggested conflicting results. The current evidence shows that compared with the population control, patients with MS have no relationship with PCa risk and further large samples and long-term trials are needed to verify these results.

Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis.

Background: Long non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of non-protein-coding RNAs. Many miRNAs have been reported to play a key role in the progression of myocardial hypertrophy. In this study, we aimed to investigate whether lncRNA reprogramming regulators (ROR) promotes hypoxic injury in cardiomyocytes by targeting and regulating the miR-145/HS1-associated protein X-1 (HAX-1) axis. Methods: A mouse model of myocardial hypertrophy was established by conventional TAC method, and the cardiomyocytes were isolated. We transfected pcDNA3.0-ROR vector, pcDNA3.0-HAX-1 vector plasmid, and miR-145 simulant into cardiomyocytes with Lipofectamine 2000. Luciferase reporter gene was used to analyze the targeting relationship between genes. Results: The expression of ROR in hypertrophic myocardium was significantly increased after phenylephrine (PE) intervention. After transfection with si-ROR, the ROR expression in hypertrophic cardiomyocytes treated with PE decreased significantly. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) decreased and superoxide dismutase (SOD) increased. The expression of miR-145 in cardiomyocytes was significantly down-regulated after PE treatment. In hypertrophic cardiomyocytes, after up-regulating the expression of miR-145, the relative messenger ribonucleic acid (mRNA) and protein expressions of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) induced by PE decreased. Compared with the miR-NC group, wild type (WT)-ROR activity in the miR-145 group was significantly inhibited (P<0.05), and mutant (MUT)-ROR activity had no significant change (P>0.05). When cardiomyocytes were transfected with HAX-1 3'URT WT vector along with miR-145 simulant, miR-145 inhibitor, and their respective controls. Compared with the control groups, the luciferase activity of cells transfected with simulant was significantly decreased (P<0.05), and increased in inhibitor group (P<0.05). Transfection of HAX-1 3'URT mutant vector did not show this phenomenon. ROR was negatively correlated with miR-145 expression and positively correlated with HAX-1 mRNA. Conclusions: The lncRNA ROR can promote the expression of HAX-1 by competitive binding with miR-145, so as to promote the pathophysiological process of myocardial hypertrophy.

Self-assembly of DNA-templated copper nanoclusters and carbon dots for ratiometric fluorometric and visual determination of arginine and acetaminophen with a logic-gate operation.

This work describes the synthesis of red-emitting copper nanoclusters (CuNCs) by using DNA as the template. DNA-templated CuNCs combined with blue-emitting carbon dots (CDs) form the self-assembled complex DNA-CuNC/CDs through electrostatic interactions. In the presence of arginine (Arg), the blue fluorescence of CDs (with excitation/emission maxima at 350/440 nm) is quenched. Addition of acetaminophen (AP) induces the competitive combination of Arg and AP for the CDs. This results in the release of Arg from CDs and the recovery of blue fluorescence. On addition of both Arg and AP, the red fluorescence of CuNCs (with excitation/emission maxima at 350/670 nm) undergoes only slight changes. Hence, the DNA-CuNC/CD complex can serve as a dually emitting ratiometric probe to determine both Arg and AP, with detection limits of 0.35 µM and 0.26 µM, respectively. The probe also enables on-site, visual determination of Arg and AP in aqueous samples, best by placing the system in cuvettes or dropping it onto filter paper strips. An "INHIBIT" logic gate was designed based on this ratiometric and visual fluorometric assay, with Arg and AP as the inputs. Graphical abstractSchematic presentation of self-assembly of DNA-templated copper nanoclusters and carbon dots to construct novel dual-emitting nanoprobes for ratiometric fluorometric and visual determination of arginine and acetaminophen in aqueous solutions and on wetting filter paper strips.

Melamine-Induced Decomposition and Anti-FRET Effect from a Self-Assembled Complex of Rhodamine 6G and DNA-Stabilized Silver Nanoclusters Used for Dual-Emitting Ratiometric and Naked-Eye-Visible Fluorescence Detection.

In this work, blue-emitting silver nanoclusters (AgNCs) were prepared in a matrix of single-stranded deoxyribonucleic acid (DNA) on the basis of ambient hydrothermal reactions. DNA acted as the stabilizer or coating agent, and NaBH4 was used as the reducing agent. Through the interactions between rhodamine 6G (Rh6G) and the synthesized DNA-AgNCs, the self-assembled complex of DNA-AgNC-Rh6G was generated. Meanwhile, fluorescence emission of AgNCs was weakened as a result of fluorescence-resonance-energy transfer (FRET) from AgNCs (donor) to Rh6G (acceptor). In the DNA-AgNC-Rh6G complex aqueous suspension, the addition of melamine induced obvious emission recovery of AgNCs and fluorescence decrease of Rh6G, attributable to melamine-induced decomposition of the self-assembled complex and anti-FRET effects. There was a well-plotted linear relationship of ratiometric fluorescence intensities ( IAgNCs/ IRh6G) versus melamine concentration in the range of 0.1-10 µM, with a low detection limit of 25 nM. Responses of IAgNCs/ IRh6G to melamine were highly selective and sensitive over potential interferents. A novel dual-emitting ratiometric fluorescence sensor of melamine was facilely constructed on the basis of the DNA-AgNC-Rh6G complex. In particular, the sensor enabled visual fluorescence detection of melamine both in aqueous solution and on wetted filter paper. Superior detection results of the sensor were experimentally obtained and confirmed its high feasibility for melamine detection in practical samples.

Ratiometric fluorescence and visual imaging detection of dopamine based on carbon dots/copper nanoclusters dual-emitting nanohybrids.

In this article, blue-emitting carbon dots (CDs) were prepared via hydrothermal treatment of sodium citrate and NH4HCO3, and then combined with 3-aminophenylboronic acid (APBA) to prepare APBA modified-CDs. APBA acted as the receptor of dopamine (DA). Using bovine serum albumin (BSA) as a stabilizer and N2H4·H2O as a reducing reagent, BSA-stabilized and red-emitting copper nanoclusters (CuNCs) were prepared. By carbodiimide-activated coupling, novel nanohybrids consisting of CDs and CuNCs were constructed and exhibited dual-emitting fluorescence (FL). In the presence of DA, marked FL (at 440nm) quenching of nanohybrids was detected. Specific coupling interactions between boric acid of APBA and cis-glycol of DA induced the combination of DA and APBA on the surface of CDs. As a superior electron receptor, DA triggered the electron transfer from CDs to DA, resulting in the FL quenching of CDs in nanohybrids. The FL (at 640nm) of CuNCs in nanohybrids was almost unchanged after the addition of DA, and so further used for a reference FL to develop a novel ratiometric FL probe for DA detection. In addition to high sensitivity and selectivity, superior analytical performances of this probe were confirmed in applications, including dual-signal FL sensing of DA and naked-eye visual FL imaging of DA in aqueous solution and on filter paper.

Everolimus (RAD001) inhibits the proliferation of rat vascular smooth muscle cells by up-regulating the activity of the p27/kip1 gene promoter.

OBJECTIVE: We investigated whether the inhibitory effect of the immunosuppressant everolimus (RAD001) on vascular smooth muscle cell (VSMC) proliferation is mediated by p27/kip1 gene promoter activity. METHODS: In this experimental study, cultured rat VSMCs were transiently transfected with a recombinant plasmid (pXp27) containing p27/kip1 gene promoter sequence and a chloramphenicol acetyltransferase (CAT) reporter gene. After stimulation with the mitogen platelet-derived growth factor (PDGF-BB, 10 ng/mL) in the presence or absence of RAD001 (10 nM), the promoter activity, mRNA expression, and protein expression of p27/kip1 were examined by CAT assay, RT-PCR, and immunoblotting, respectively. Cell cycle-related changes were detected by flow cytometry. DNA synthesis was determined using 3H-TdR incorporation. RESULTS: Compared with the non-stimulation group, PDGF-BB stimulation induced a significant proliferative response in the VSMCs as indicated by decreased p27/kip1 gene promoter activity, decreased p27/kip1 mRNA and protein expression, increased S-phase and G2/M-phase cells, and increased DNA synthesis. RAD001 intervention increased p27/kip1 gene promoter activity 3.5-fold, promoted p27/kip1 mRNA and protein expression, increased G0-phase cells, reduced DNA synthesis, and, overall, inhibited PDGF-BB-stimulated cell proliferation. CONCLUSION: RAD001 inhibits PDGF-BB-stimulated proliferation of cultured VSMCs by upregulating p27/kip1 gene promoter activity and increasing p27/kip1 mRNA and protein expression.

[Treatment of fracture of tibia and fibula with three dimensional diaplasis fixation].

OBJECTIVE: To study the clinical effect of three dimensional diaplasis fixation in fracture of tibia and fibula. METHODS: Twenty-one cases of fracture of tibia and fibula were treated with three dimensions fixation (12 males, 9 females, with an average age of 46 years). There were 5 cases in open fracture, 16 cases in closed fracture, and 4 cases in up-segment fracture, 8 cases in mid-segment fracture, 9 cases in below-segment fracture. Oblique fracture were in 10 cases, thrypsis were in 8 cases, multisegmental fracture were in 3 cases. RESULTS: (1) Conditions of diaplasis fracture: dissected diaplasis were in 11 cases, closely dissected diaplasis in 9 cases, functional diaplasis in 1 case. (2) Clinical healing time: the minimum time was 43 days and maximum time was 85 days with an average of 62 days. (3) Conditions of functional recovery: all the patients were followed up from 4 to 12 months, 13 cases were excellent, 8 cases were good. (4) Time of backouting three dimensional diaplasis fixation: the minimum time was 6 weeks and the maximum 12 weeks with an average time of 8.5 weeks. CONCLUSION: The three dimensional diaplasis fixation and the fracture extremity from such a three dimensional solid that it can satisfy crus biomechanics for treating fracture of tibia and fibula with unstressed barrier and uncentric stress. Moreover, the three dimensional diaplasis fixation is elastic, it's structure is so fixed that it can be favorable for bone union.