Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer.

Urinary bladder neoplasm is one of the most common cancers worldwide. Cancer stem cells (CSCs) have been proven to be an important cause of cancer progression and poor prognosis. In the present study, we established bladder CSCs and identified the crucial differentially expressed genes (DEGs) between these cells and parental bladder cancer cells. Analyses of bioinformatics data and clinical samples from local hospitals showed that stearoyl CoA desaturase-1 (SCD) was the key factor among the DEGs. A significant correlation between SCD gene expression and poor prognosis among patients with bladder cancer was observed in our data. Loss-of-function experiments further revealed that the SCD inhibitor A939572 and SCD gene interference reduced cell proliferation and invasion. The above data suggest that SCD may serve as a novel marker for the prediction of tumour progression and poor prognosis in patients with bladder cancer.

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma.

In light of the increasing incidence of renal cell carcinoma (RCC), its molecular mechanisms have been comprehensively explored in numerous recent studies. However, few studies focus on the influence of multi-factor interactions during the occurrence and development of RCC. This study aims to investigate the quantitative global proteome and the changes in lysine succinylation in related proteins, seeking to facilitate a better understanding of the molecular mechanisms underlying RCC. LC-MS/MS combined with bioinformatics analysis are used to quantitatively detect the perspectives at the global protein level. IP and WB analysis were conducted to further verify the alternations of related proteins and lysine succinylation. A total of 3,217 proteins and 1,238 lysine succinylation sites are quantified in RCC tissues, and 668 differentially expressed proteins and 161 differentially expressed lysine succinylation sites are identified. Besides, expressions of PGK1 and PKM2 at protein and lysine, succinylation levels are significantly altered in RCC tissues. Bioinformatics analysis indicates that the glycolysis pathway is a potential mechanism of RCC progression and lysine succinylation may plays a potential role in energy metabolism. These results can provide a new direction for exploring the molecular mechanism of RCC tumorigenesis.

TGF-ß1 induced fascin1 expression facilitates the migration and invasion of kidney carcinoma cells through ERK and JNK signaling pathways.

Transforming growth factor-ß1 (TGF-ß1) plays a crucial role in the signaling network that controls cellular invasion and motility capability during tumor development. To investigate whether fascin1 plays a crucial role in TGF-ß1-facilitated invasion and migration of kidney cancer cells (KCC), real-time PCR and western blotting were used to test the fascin1 expression after TGF-ß1 treatment (10 ng/ml) in 769-P and OSRC cells. Fascin1 was silenced using the small interfering RNA (siRNA) technique. Cytoskeleton staining was used to test the change of Cytoskeleton. Cell migration and invasion changes were measured by wound-healing and Transwell assay. The results indicate that mRNA and protein levels of fascin1 were dramatically increased after treatment with 10 ng/ml TGF-ß1 in 769-P and OSRC cells. TGF-ß1 promoted the occurrence of EMT (Epithelial-Mesenchymal Transition) and the invasive and migratory capabilities of the two cell lines after treatment with 10 ng/ml TGF-ß1. In addition, fascin1 siRNA dramatically attenuated the invasiveness and migration induced by TGF-ß1. Furthermore, we identified that specific inhibitors of ERK and JNK signaling pathways, FR180204 and SP600125, can suppress TGF-ß1-induced fascin1 expression. In conclusion, these results reveal that fascin1 is an important mediator of TGF-ß1-induced invasion and migration of KCC through ERK and JNK signal pathways.

Bibliometric Analysis of Tumor Immunotherapy Studies.

BACKGROUND Cancer immunotherapy is the use of the immune system to treat cancer. After years of research, there have been a significant number of publications in this field. We analyzed the literature and performed a hotspot analysis to identify important areas of future scientific research. MATERIAL AND METHODS Articles (2945) related to cancer immunotherapy published in the past 3 years were selected as the research sample. BICOMB software was then used to retrieve the high-frequency words and construct a text/co-word matrix. Next, gCLUTO software was used to analyze the matrix by double-clustering and visual analysis, in a strategy of hotspot identification. RESULTS We constructed a text and co-word matrix composed of 40 high-frequency words and 2945 articles and generated a hotspot "peak map" based on double-clustering analysis. The strategic coordinates were set by use of a co-word matrix and clustering analysis. The distribution of organs or disease and the subclass of cancer immunotherapy were analyzed. CONCLUSIONS In this study, we classified the hot-spots of "tumor immunotherapy" into 6 categories and 8 aspects. Calculation and analysis revealed that the field of tumor immunotherapy shows a slight trend of polarization, and the immune checkpoint inhibitor PD1 blocker shows the greatest potential for future development.

Comprehensive analysis of differentially expressed genes associated with PLK1 in bladder cancer.

BACKGROUND: The significance of PLK1 (polo-like kinase 1) has become increasingly essential as both a biomarker and a target for cancer treatment. Here, we aimed to determine the downstream genes of PLK1 and their effects on the carcinogenesis and progression of bladder cancer. METHODS: Specific siRNA was utilized to silence the target gene expression. The cell proliferation, invasion and migration of bladder cancer cells by MTT assay, BrdU assay and transwell assay. The differential expression genes were identified using Affymetrix HTA2.0 Array. The KEGG, GO and STRING analysis were used to analyze the signaling pathway and protein-protein interaction. Spearman analysis was used to analyze the correlation between protein and protein, between protein and clincopathologic characteristics. RESULTS: PLK1 siRNA hindered the proliferation, invasion and migration of bladder cancer cells, as determined by the MTT, BrdU and transwell assays. A total of 561 differentially expressed genes were identified using an Affymetrix HTA2.0 Array in PLK1 knockdown T24 cells. According to KEGG, GO and STRING analysis, five key genes (BUB1B, CCNB1, CDC25A, FBXO5, NDC80) were determined to be involved in cell proliferation, invasion and migration. PLK1 knockdown decreased BUB1B, CCNB1, CDC25A and NDC80 expressions but increased FBXO5 expression. BUB1B, CCNB1, CDC25A and NDC80 were positively correlated with cell proliferation, invasion, migration and PLK1 expression in tissues, but FBXO5 was negatively correlated with each of those factors. The results showed that the five genes expressions were significantly correlation with the PLK1 expression in normal bladder tissues and bladder cancer tissues. Four of them (BUB1B, CCNB1, CDC25A, NDC80) were obviously positive correlations with pT stage and metastasis. But FBXO5 was negative correlated with pT stage and metastasis. Furthermore, significant correlations were found between CCNB1 or CDC25A or NDC80 and histological grade; between BUB1B or NDC80 and recurrence. CONCLUSION: Five downstream genes of PLK1 were associated with the regulation of cell proliferation, invasion and migration in bladder cancer. Furthermore, these genes may play important roles in bladder cancer and become important biomarkers and targets for cancer treatment.

Nitrogen-Doped Carbon Quantum Dots as Fluorescent Probes for Sensitive and Selective Detection of Nitrite.

Nitrites are the upstream precursors of the carcinogenic nitrosamines, which are widely found in the natural environment and many food products. It is important to develop a simple and sensitive sensor for detecting nitrites. In this work, a fluorescence probe based on nitrogen-doped carbon quantum dots (N-CQDs) was developed for the sensitive and selective determination of nitrites. At pH 2, the fluorescence of N-CQDs can be selectively quenched by nitrite due to the fact N-nitroso compounds can be formed in the reaction of amide groups with nitrous acid, which results in fluorescence static quenching. Under optimal conditions, fluorescence intensity quenching upon addition of nitrite gives a satisfactory linear relationship covering the linear range of 0.2-20 µM, and the limit of detection (LOD) is 40 nM. Moreover, this method has been successfully applied to the determination of nitrites in tap water, which indicates its great potential for monitoring of nitrites in environmental samples.

Impact of lipoprotein(a) and fibrinogen on prognosis in patients with coronary artery disease: A retrospective cohort study.

BACKGROUND: Despite the considerable progress made in preventative methods, medication, and interventional therapies, it remains evident that cardiovascular events (CVEs) continue to be the primary cause of both death and morbidity among individuals diagnosed with coronary artery disease (CAD). OBJECTIVE: To compare the connection between lipoprotein a (Lp[a]), fibrinogen (Fib), and both parameters combined with all-cause mortality to detect their value as prognostic biomarkers. METHODS: This is a retrospective study. Patients diagnosed with CAD between January 2007 and December 2020 at the Guangdong Provincial People's Hospital (China) were involved in the study. 43,367 patients met the eligibility criteria. The Lp(a) and Fib levels were distributed into three tertile groups (low, medium, and high). All of the patients included in the study were followed up for all-cause mortality. Kaplan-Meier and Cox regression were performed to determine the relationship between Lp(a), Fib, and all-cause mortality. A concordance statistics model was developed to detect the impact of Fib and Lp(a) in terms of anticipating poor outcomes in patients with CAD. RESULTS: Throughout a median follow-up of 67.0 months, 6,883 (15.9%) patients died. Participants with high Lp(a) (above 27.60 mg/dL) levels had a significantly higher risk for all-cause mortality than individuals with low Lp(a) levels (below 11.13 mg/dL; adjusted hazard ratio [aHR] 1.219, 95% confidence interval [CI]: 1.141-1.304, p< 0.001). Similarly, patients with high Fib levels (above 4.32 g/L) had a significantly greater risk of developing all-cause mortality compared with those with reduced Fib levels (below 3.41 g/L; aHR 1.415, 95% CI: 1.323-1.514, p< 0.001). Patients with raised Lp(a) and Fib levels had the maximum risk for all-cause mortality (aHR 1.702; 95% CI: 1.558-1.859, p< 0.001). When considered together, Lp(a) and Fib caused a significant elevation of the concordance statistic by 0.009 (p< 0.05), suggesting a higher value for predicting mortality when combining the two indicators. CONCLUSION: High Lp(a) and Fib levels could be used as predictive biomarkers for all-cause mortality in individuals with CAD. The prediction accuracy for all-cause mortality improved after combining the two parameters.

The High-Sensitivity C-Reactive Protein to High-Density Lipoprotein Cholesterol Ratio and the Risk of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention.

Background: The high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (CHR) is a novel biomarker associated with coronary artery disease (CAD) risk. This study aimed to analyze the relationship between CHR and contrast-induced acute kidney injury (CI-AKI). Methods: This retrospective cross-sectional research included 10,917 individuals who underwent PCI. CI-AKI was diagnosed using the Kidney Disease: Improving Global Outcomes (KIDIGO) standard. Univariate and multivariable logistic regression analyses were conducted to examine the association between CHR and CI-AKI, followed by a receiver operating characteristic (ROC) curve of participants to assess the clinical diagnostic performance of CHR on CI-AKI. Results: A total of 1037 patients (9.50%) developed CI-AKI after PCI. The age of individuals averaged 64.1 ± 11.1 years old, with 2511 females (23.0%). A multivariate logistic regression study revealed that higher CHR levels were linked to higher CI-AKI incidence rates ([Q4 vs. Q1]: odds ratio (OR) = 1.89, 95% confidence interval (CI) [1.42 to 2.54], p < 0.001). A restricted cubic spline analysis revealed a linear association between CHR and CI-AKI. ROC analysis indicated that CHR was an excellent predictor of CI-AKI (area under ROC curve = 0.606, 95% CI [0.588 to 0.624]). Conclusions: A high CHR level is strongly associated with increased CI-AKI incidence, suggesting that CHR may be an independent risk factor for CI-AKI. Clinical Trial registration: NCT05050877. https://clinicaltrials.gov/study/NCT05050877?tab=results.

[Corrigendum] Knockdown of SNHG15 suppresses renal cell carcinoma proliferation and EMT by regulating the NF­κB signaling pathway.

Subsequently to the publication of the above article, the authors have realized that, on p. 390, the data selected for the siRNA­1 and siRNA­2 experiments for the ACHN and 786-O cell lines concerning both the invasion and the migration assays in Fig. 4B were selected inappropriately. Furthermore, after having inspected the published version of Fig. 5, the authors have realized that, for the immunofluorescence experiments shown in Fig. 5D, the first 'Merged' pictures for the first two columns of the ACHN cell line were accidentally published in the wrong order. The corrected versions of Figs. 4, and 5, including all the correct data for Figs. 4B and 5D, are shown on the next three pages. The authors confirm that these data continue to support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 53: 384­394, 2018; DOI: 10.3892/ijo.2018.4395].

Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1.

MicroRNAs (miRNAs) are small, noncoding ribonucleic acids (ncRNAs), which regulate gene expression by targeting mRNAs for translational repression and degradation. Several lines of evidences have indicated that miRNAs act as tumor suppressors and oncogenes. However, the role of miRNAs in pathogenesis of multiple myeloma (MM) remains unclear. In this study, we examined the profile of miRNA expression of primary MM cells, using miRNA microarray and quantitative real-time polymerase chain reaction (qPCR) techniques. These results showed that in the bone marrow specimens analyzed, miRNA-29b was significantly downregulated. Similar results were also observed in human myeloma cell lines (HMCLs). Adenovirus-mediated overexpression of miR-29b induced apoptosis and elevated caspase-3 activation in HMCLs. Using a bioinformatics approach, we found a perfect complementarity between miRNA-29b and the 3'UTR of myeloid-cell-leukemia 1(Mcl-1). It is further confirmed that miRNA-29b downregulated the level of Mcl-1 without effect on the mRNA level using both qRT-PCR assays and Western blot analyses. Moreover, we observed that enforced miR-29b expression by using a retarget miRNA-29b expression vector (Ad5F11p-miR-29b) could induce apoptosis and elevate caspase-3 activation in HMCLs. Our results also indicated that miRNA-29b-induced apoptosis acted antagonistically with IL-6 in HMCLs. These findings suggest that miRNA-29b may play an important role in MM as a tumor suppressor.

iASPP is important for bladder cancer cell proliferation.

Inhibitor of apoptosis stimulatory protein phosphatase (iASPP) is a key inhibitor of p53 conserved from worm to human and is associated with cell proliferation and carcinogenesis in a variety of human cancers. Because iASPP is important for tumor cell apoptosis, it is a potential target for cancer gene therapy. However, it is still not clear whether iASPP is relevant to p53-deficient human bladder cancer. In the present study, iASPP was knocked down in bladder carcinoma 5637 and T24 cells (p53 defective) by lentiviral-mediated interfering short hairpin RNAs (siRNAs). MTT assay, BrdU incorporation assay, and colony formation assay were performed to investigate the role of iASPP on cell proliferation. It was suggested that iASPP knockdown led to cell growth deceleration and slow colony formation. A positive relationship between expression of iASPP and bladder cancer proliferation was found. The expression of iASPP may be critical for proliferation of bladder cancer cells. Our study indicates iASPP could be an important target for therapy in bladder cancer.

Chemically modified self-doped biocarbon via novel sulfonation assisted sacrificial template method for high performance flexible all solid-state supercapacitor.

The development of lignin-based carbon electrodes for high-performance flexible, solid-state supercapacitors in next-generation soft and portable electronics, has received much attention. Herein, a self-doped multi-porous lignin-based biocarbon (SUMBC) has been prepared via a simple sulfonation assisted sacrificial template method for the effective formation of oxygenated C-S-C moieties in the carbon network. In this proposed method, the sulfonate moieties in lignin are responsible for the successful decoration of oxygen enriched C-S-C moieties as well as for creating the optimal multilevel porous architecture (ultra-micropores, micropores and mesopores) in the carbon matrix with a large surface area (3149 m2 g-1). Because the sulfonate functionalities yield more sulfur species and induce further defects into carbon framework, in the activation process, these sulfur functionalities produce additional narrow micropores. Benefiting from the above unique feature, the supercapacitor (SC) with the SUMBC electrode delivers excellent capacitive behavior in both acidic (2 M H2SO4) and alkaline (6 M KOH) liquid electrolytes. More prominently, the all-solid state, symmetric supercapacitors assembled by SUMBC show outstanding capacitance of ~140 F g-1 at 0.5 A g-1 in two different devices and reveals high energy density (~5.41 W h kg-1 at 0.5 k W kg-1 power density) and excellent stability. In addition, the solid-state supercapacitors manifest a remarkable flexibility at different bending angles. Hence, the present work provides a new strategy for the preparation of efficient biocarbons via a facile sulfonation assisted sacrificial template method; moreover, the high-performance all-solid supercapacitors based on sulfonated modified lignin has great potential in the field of portable and wearable energy storage devices.

PLK1 promotes proliferation and suppresses apoptosis of renal cell carcinoma cells by phosphorylating MCM3.

Minichromosome maintenance 3 (MCM3) protein has been widely studied due to its essential role in DNA replication. In addition, it is overexpressed in several human tumor types. However, the role of this protein in renal cell carcinoma (RCC) is not widely known. In this study, we demonstrated that polo-like kinase 1 (PLK1)-mediated MCM3 phosphorylation regulates proliferation and apoptosis in RCC. Our results confirm that PLK1 and phospho-MCM3 (p-MCM3) are highly expressed in renal cell carcinoma. The expression of PLK1 is closely related to the clinical characteristics of renal cell carcinoma. They play important roles in the proliferation and apoptosis of RCC. In vitro, after overexpression of PLK1 or MCM3, the proliferation of RCC cells was significantly enhanced and cell apoptosis was inhibited, while after knockout, the proliferation of RCC cells was weakened and cell apoptosis was promoted. In addition, Mn2+-Phos-tag SDS-PAGE, western blotting, and immunofluorescence were utilized to determine that MCM3 is a physiological substrate of PLK1, which is phosphorylated on serine 112 (Ser112) in a PLK1-dependent manner. PLK1-mediated MCM3 phosphorylation promotes RCC cell cycle proliferation and suppresses apoptosis in vitro. Moreover, we found that PLK1-mediated MCM3 phosphorylation induced cellular proliferation and decreased apoptosis, as well as tumor growth in mice. Overall, we conclude that PLK1-mediated MCM3 phosphorylation is a novel mechanism to regulate RCC proliferation and apoptosis.

The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer.

Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3'-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues. Furthermore, circINTS4 was found to control multiple pathological processes, including cell proliferation and migration, the cell cycle and apoptosis. Regarding the mechanism, circINTS4 directly bound to miR-146b to inhibit its activity of targeting the 3'-UTR of CARMA3 mRNA. In addition, circINTS4 could activate the NF-kB signalling pathway and suppress the P38 MAPK signalling pathway in a CARMA3-mediated manner in BC cells. In summary, the circINTS4/miR-146b/CARMA3 axis might serve as a promising therapeutic target for BC intervention.

Cost-Effective Monolithic Hierarchical Carbon Cryogels with Nitrogen Doping and High-Performance Mechanical Properties for CO2 Capture.

Cost-effective nitrogen-doped monolithic hierarchical carbon cryogels with excellent mechanical properties and carbon dioxide (CO2) adsorption performance were prepared from phenol, melamine, and formaldehyde (PMF) by the sol-gel, freeze-drying, and then, pyrolysis processes under an inert atmosphere. The morphology, mechanical properties, pore structure, and chemical characteristics of these cryogels were investigated. The results showed that the dilution ratio played a crucial role in the preparation of nitrogen-doped PMF carbon cryogels with controlled structures. The prepared carbon cryogels were a kind of monolithic materials composed of a hierarchical pore structure and had high compression properties (0.67 and 9.4 MPa for strength and modulus), porosity (97.6%), surface area (1406 m2/g), and heteroatom nitrogen content (0.98-2.09%). CO2 adsorption capacities up to 5.75 mmol/g at 0 °C and 4.50 mmol/g at 25 °C under 1 bar were obtained, which is at a high level among N-doped carbon materials and far better than resorcinol-based carbon gels reported. These superior CO2 adsorption capacities, high isosteric adsorption heat (Qst), and good CO2/N2 adsorption selectivity were ascribed to the synergistic effect of high surface area, appropriate pore size, and also heteroatom doping.

[Diagnosis and treatment for the corticomedullary mixed tumor of adrenal gland].

OBJECTIVE: To study and summarize the diagnosis and treatment for the corticomedullary mixed tumor of adrenal gland. METHODS: The clinical data of 25 cases of adrenal corticomedullary mixed tumor from January 2000 to April 2008 were analyzed retrospectively, which including 9 males and 16 females. The ages were from 25 to 60 years old, and the average age was 39 years old. Thirteen cases had paroxysmal hypertension and 11 cases had central obesity, as well as 8 cases with hypokalemia. There were different degree abnormalities in plasma endocrine hormones in laboratory examination. Every case underwent b-ultrasound and CT normal plus extensive scan to make the diagnosis. RESULTS: Adrenalectomy was performed in the 25 cases, which contain 9 cases of open operations and 16 cases of endoscopic adrenalectomies. All of the cases had blood pressure fluctuation during dissection of the adrenal tumors, with the highest blood pressure reached to 230/140 mm Hg (1 mm Hg = 0.133 kPa). Postoperative histopathological study revealed that the pathological changes was corticomedullary mixed tumor of adrenal gland, which was supported by immunohistochemical study. CONCLUSIONS: In cases with complex phenomenon that can't explain with single cortical or medullary changes, it must beware of the mixed pathological changes in adrenal gland.

Synthesis of activated carbon from biowaste of fir bark for methylene blue removal.

Activated carbon (AC) was successfully prepared from low-cost forestry fir bark (FB) waste using KOH activation method. Morphology and texture properties of ACFB were studied by scanning and high-resolution transmission electron microscopies (SEM and HRTEM), respectively. The resulting fir bark-based activated carbon (ACFB) demonstrated high surface area (1552 m2 g-1) and pore volume (0.84 cm3 g-1), both of which reflect excellent potential adsorption properties of ACFB towards methylene blue (MB). The effect of various factors, such as pH, initial concentration, adsorbent content as well as adsorption duration, was studied individually. Adsorption isotherms of MB were fitted using all three nonlinear models (Freundlich, Langmuir and Tempkin). The best fitting of MB adsorption results was obtained using Freundlich and Temkin. Experimental results showed that kinetics of MB adsorption by our ACFB adsorbent followed pseudo-second-order model. The maximum adsorption capacity obtained was 330 mg g-1, which indicated that FB is an excellent raw material for low-cost production of AC suitable for cationic dye removal.

Expression profiles analysis identifies the values of carcinogenesis and the prognostic prediction of three genes in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare disease associated with a poor prognosis. Furthermore, the underlying molecular mechanism of carcinogenesis is poorly understood, and prognostic prediction of ACC has low accuracy. In the present study, a bioinformatics approach was used to investigate the molecular mechanisms and prognosis of ACC. Samples of adrenal tumors were collected from patients undergoing adrenalectomy at the Department of Urology, the First Hospital of China Medical University. The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein­protein interaction network and survival analyses. MTT colorimetric assays, colony formation assays and 5­ethynyl­20­deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. The identified DEGs included 20 downregulated genes and 51 upregulated genes, which were highly associated with the cell cycle, organelle fission, chromosome segregation, cell division and spindle stability. The top 14 hub genes were subsequently confirmed by reverse transcription­quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2­α may serve important roles in adrenocortical tumor development. Furthermore, these three genes predicted overall survival and recurrence­free survival in patients with ACC from the TCGA cohort. The findings identified three novel genes that have important roles in carcinogenesis and in the prognostic prediction of ACC.

Olmesartan Medoxomil, An Angiotensin II-Receptor Blocker, Ameliorates Renal Injury In db/db Mice.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established. METHODS: Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed. RESULTS: Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice. CONCLUSION: Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.