Vertebral HU value and the pectoral muscle index based on chest CT can be used to opportunistically screen for osteoporosis.

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment. METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The T4 HU value and PMI were obtained using manual chest CT measurements. The participants were classified into normal, osteopenia, and osteoporosis groups based on the results of dual-energy X-ray (DXA) absorptiometry. We compared the clinical baseline data, T4 HU value, and PMI between the three groups of patients and analyzed the correlation between the T4 HU value, PMI, and BMD to further evaluate the diagnostic efficacy of the T4 HU value and PMI for patients with low BMD and osteoporosis. RESULTS: The study ultimately enrolled 469 participants. The T4 HU value and PMI had a high screening capacity for both low BMD and osteoporosis. The combined diagnostic model-incorporating sex, age, BMI, T4 HU value, and PMI-demonstrated the best diagnostic efficacy, with areas under the receiver operating characteristic curve (AUC) of 0.887 and 0.892 for identifying low BMD and osteoporosis, respectively. CONCLUSIONS: The measurement of T4 HU value and PMI on chest CT can be used as an opportunistic screening tool for osteoporosis with excellent diagnostic efficacy. This approach allows the early prevention of osteoporotic fractures via the timely screening of individuals at high risk of osteoporosis without requiring additional radiation.

Population pharmacokinetics of adebrelimab - Support of alternative flat dose regimen in extensive-stage small-cell lung cancer.

Adebrelimab, a novel anti-PD-L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer in 2023. A two-compartment model with empirical time-varying CL for adebrelimab was established based on data from 263 patients receiving body weight-based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti-drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non-responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure-response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight-based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic.

Microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug.

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China.

BACKGROUND: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020-2022. METHOD: We collected HIV incidence and mortality data from the website of the National Health Commission of the People's Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020-2022 with those in 2015-2019 using a two-ratio Z-test. RESULTS: From January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015-2019 (pre-COVID-19 stage) and 2020-2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p <  0.001) in 2020-2022 compared with that in 2015-2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p <  0.001), in 2020-2022 compared with those in 2015-2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015-2019, while the incidence during the routine stage in May 2020-December 2022 increased by 27.4334%, (all p <  0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p <  0.001). CONCLUSIONS: The findings suggest that China's dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without China's dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020-2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.

A single-centre, open-label, single-arm, fixed-sequence pharmacokinetic study of SHR3680 on repaglinide and bupropion in prostate cancer patients.

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion. METHODS: A single-centre, open-label, single-arm, fixed-sequence clinical trial in 18 patients with prostate cancer. RESULTS: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (Cmax ) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration-time curve (AUC0-t )was 20.577 and 7.320 h ng/mL, geometric mean AUC0-∞ was 20.949 and 7.451 h ng/mL, mean half-life (t1/2 ) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean Cmax of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC0-t was 1003.896 and 380.158 h ng/mL, geometric mean AUC0-∞ was 1038.054 and 401.387 h ng/mL, mean t1/2 was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean Cmax of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC0-t was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC0-∞ was 15 218.158 and 5364.625 h ng/mL, mean t1/2 were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively. CONCLUSION: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half-lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion.

Analysis of Influencing Factors of Unplanned Readmission in Patients With Acute Coronary Syndrome Within 30 Days After PCI.

OBJECTIVE: The purpose of this study is to identify the influencing factors of unplanned readmission in patients with the acute coronary syndrome (ACS) within 30 days after percutaneous coronary intervention (PCI). METHODS: From November 1, 2018, to October 31, 2019, the clinical data of 1277 patients with acute coronary syndrome and percutaneous coronary intervention retrospectively were collected. After screening by exclusion and rejection criteria, a total of 936 patients finally entered the study. Patients were divided into the readmission group (57 cases) and the non-readmission group (879 cases), according to whether unplanned readmission occurred within 30 days after PCI. To analyze the influence of patients' age, past disease history, medication history, laboratory data, vascular diseases, and other factors on readmission and the clinical characteristics of readmission patients. RESULTS: Fifty-seven patients had unplanned readmission within 30 days, and the readmission rate was 6.09%. The clinical features of readmission patients are older age, longer hospitalization days, more emergency percutaneous coronary intervention, more patients with diabetes history, and more patients diagnosed with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. Logistic regression analysis revealed that smoking index, number of diseased vessels, ACEF score, diabetes, and PCI status were the influencing factors of unplanned readmission of ACS patients within 30 days after PCI. CONCLUSION: Smoking index, number of diseased vessels, ACEF score, diabetes, and PCI status are the influencing factors of unplanned readmission within 30 days after percutaneous coronary intervention for patients with acute coronary syndrome.

Application of physiologically based pharmacokinetic modelling for the prediction of drug-drug interactions involving anlotinib as a perpetrator of cytochrome P450 enzymes.

Anlotinib is a small molecule of novel tyrosine kinase inhibitor initially approved to treat non-small cell lung cancer in China. Drug-drug interaction (DDI) is an extrinsic factor important for the appropriate use of anlotinib in clinical practice. In vitro experiments demonstrated that anlotinib is a substrate of cytochrome P450 (CYP) enzymes and moderate inhibitor of several common ones; however, no clinical DDI studies have been performed to investigate inhibitory effects of anlotinib on these CYP enzymes. Thus, its drug label recommends avoiding co-administration with substrates of these enzymes, which have narrow therapeutic windows. In this study, we performed a CYP450 inhibition study, followed by gathering in vitro and clinical pharmacokinetic data to build the first physiologically based pharmacokinetic (PBPK) model of anlotinib. The verified model was subsequently used to predict the DDI mediated by anlotinib. As a result, the marginal plasma exposure changes of typical CYP3A and CYP2C9 substrates were less than the bioequivalence threshold, indicating that anlotinib has a very low potential of causing clinically meaningful DDI through the inhibition of several major CYP enzymes. According to the FDA's latest guideline on DDI, the established model with the simulation results may support the revision of anlotinib labelling without further clinical studies, lifting unnecessary restrictions on anlotinib regimens.

MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH.

This study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.

Downregulation of long non-coding RNA MR4435-2HG suppresses breast cancer progression via the Wnt/ß-catenin signaling pathway.

Extensive research has contributed to the current understanding of the critical roles played by long non-coding RNAs in various types of cancer. The present study aimed to investigate the function and mechanism of the long non-coding RNA, MIR4435-2HG (also termed LINC00978), in breast cancer growth and metastasis. Using Gene Expression Profiling Interactive Analysis, an online web tool, it was revealed that MIR4435-2HG was upregulated in breast cancer tissue, and its high expression was associated with poor prognosis based on The Cancer Genome Atlas database. MIR4435-2HG knockdown increased cell apoptosis but decreased cell proliferation, migration and invasion. MIR4435-2HG knockdown increased pro-apoptotic protein expression but decreased anti-apoptotic protein expression. In addition, MIR4435-2HG knockdown leads to dysregulation of epithelial-to-mesenchymal transition-associated genes. Furthermore, knockdown of MIR4435-2HG results in inactivation of the Wnt/ß-catenin signaling pathway. The results of the present study demonstrate the tumor-promoting role of MIR4435-2HG in breast cancer progression.

Ethylene glycol and glycolic acid production from xylonic acid by Enterobacter cloacae.

BACKGROUND: Biological routes for ethylene glycol production have been developed in recent years by constructing the synthesis pathways in different microorganisms. However, no microorganisms have been reported yet to produce ethylene glycol naturally. RESULTS: Xylonic acid utilizing microorganisms were screened from natural environments, and an Enterobacter cloacae strain was isolated. The major metabolites of this strain were ethylene glycol and glycolic acid. However, the metabolites were switched to 2,3-butanediol, acetoin or acetic acid when this strain was cultured with other carbon sources. The metabolic pathway of ethylene glycol synthesis from xylonic acid in this bacterium was identified. Xylonic acid was converted to 2-dehydro-3-deoxy-D-pentonate catalyzed by D-xylonic acid dehydratase. 2-Dehydro-3-deoxy-D-pentonate was converted to form pyruvate and glycolaldehyde, and this reaction was catalyzed by an aldolase. D-Xylonic acid dehydratase and 2-dehydro-3-deoxy-D-pentonate aldolase were encoded by yjhG and yjhH, respectively. The two genes are part of the same operon and are located adjacent on the chromosome. Besides yjhG and yjhH, this operon contains four other genes. However, individually inactivation of these four genes had no effect on either ethylene glycol or glycolic acid production; both formed from glycolaldehyde. YqhD exhibits ethylene glycol dehydrogenase activity in vitro. However, a low level of ethylene glycol was still synthesized by E. cloacae ΔyqhD. Fermentation parameters for ethylene glycol and glycolic acid production by the E. cloacae strain were optimized, and aerobic cultivation at neutral pH were found to be optimal. In fed batch culture, 34 g/L of ethylene glycol and 13 g/L of glycolic acid were produced in 46 h, with a total conversion ratio of 0.99 mol/mol xylonic acid. CONCLUSIONS: A novel route of xylose biorefinery via xylonic acid as an intermediate has been established.

Flexible Three-Dimensional Net for Intravascular Fishing of Circulating Tumor Cells.

Current strategies for in vitro isolation of circulating tumor cells (CTCs) fail to detect extremely rare CTCs heterogeneously distributed in blood. It is possible to devise methods for in vivo capture of CTCs based on processing almost all of the blood in the human body to improve detection sensitivity, but the complicated manipulation, biosafety concerns, and limited capture efficiency of conventional detection strategies prohibit their implementation in the clinic. Herein, we present a flexible three-dimensional (3-D) CTC-Net probe for intravascular collection of CTCs. The CTC-Net, consisting of a 3-D elastic scaffold with an interconnected, spatially distributed network accommodates a large quantity of immobilized antibodies and provides an enhanced substrate-cell contact frequency, which results in an enhanced capture efficiency and effective detection of heterogeneous CTCs. The as-prepared CTC-Net can be readily compressed and injected into blood vessels and fully unfolded to form a 3-D "fishing-net" structure for capture of the CTCs, and then retracted for imaging and downstream gene analysis of the captured CTCs. Significant advantages for the CTC-Net over currently available in vitro and in vivo procedures are demonstrated for detection of extremely rare CTCs from wild-type rats and successful capture of CTCs and CTC clusters before metastasis in the case of tumor-bearing rats. Our research demonstrates for the first time the use of a 3-D scaffold CTC-Net probe for in vivo capture of CTCs. The method shows exceptional performance for cell capture, which is readily implemented and holds great potential in the clinic for early diagnosis of cancer.

Spexin protects cardiomyocytes from hypoxia-induced metabolic and mitochondrial dysfunction.

Spexin (SPX) is a novel peptide with pleiotropic functions in adipose tissue including energy balance adjustment, fatty acid uptake, and glucose homeostasis. SPX level is closely associated with cardiovascular risk factors such as age, obesity, hypertension, and diabetes; however, its physiological significance in the cardiovascular system remains mostly undefined. We therefore here investigated the roles of SPX in regulating hypoxia-induced alterations in energy metabolism and mitochondrial function. We firstly confirmed that SPX is expressed in human and mouse cardiac tissue and documented that exposure to hypoxia in vitro reduces SPX level in rat H9C2 cardiomyocytes and primary neonatal rat ventricular myocytes (NRVMs). We then treated primary NRVMs with SPX before exposure to hypoxia, which (1) promoted fatty acid metabolism by enhancing expression of FAT/CD36, CPT1, ACADM, and PPAR-a and PGC1-a; (2) did not improve impaired glucose uptake; and (3) significantly prevented the downregulation of TFAM and mitochondrial electron transport chain complex and restrained UCP2 level and reactive oxygen species (ROS) production, thus enhancing ATP level in cardiomyocytes. In summary, SPX protects energy and mitochondrial homeostasis of cardiomyocytes during hypoxia, thereby highlighting the potential importance of SPX in the treatment of cardiovascular diseases.

Small RNA sequencing reveals a novel tsRNA-26576 mediating tumorigenesis of breast cancer.

Purpose: As a malignancy that develops from breast tissue, breast cancer has been widely regarded as the most common type of cancer threatening the health of women worldwide. Emerging evidence has demonstrated that tsRNAs might play a vital part in the tumorigenesis and progression of several types of cancers. However, the functions of tsRNAs in breast cancer remain largely unknown. Here, we investigated the functions of tsRNA-26576 in tumorigenesis of breast cancer. Patients and methods: In this study, the tsRNA deregulation states in breast cancer patients (four cancer tissues and four adjacent normal tissues) were evaluated using small RNA sequencing. And then, RT-PCR was used to detected the tsRNA-26576 expression level in breast cancer patients. Results: A total of 263 tsRNAs were identified as significantly differentially expressed, of which 75 were upregulated, and 188 were downregulated. The functional classification through KEGG pathway database illustrated that the most significant pathway enriched by the targets of differentially expressed tsRNAs was the pathway in cancer. Among these differently expressed tsRNAs, we found that tsRNA-26576 was remarkably upregulated in cancer tissue in comparison with adjacent normal tissue. Meanwhile, RT-PCR results verified that tsRNA-26576 expression level was highly upregulated in 10 paired samples from breast cancer patients. Besides, tsRNA-26576 was found to motivate cellular multiplication and migration while suppressing cellular apoptosis in MDA-MB-231 cells. Moreover, mRNA sequencing results showed that several tumor suppressor genes, including FAT4 and SPEN, were upregulated after delivering tsRNA-26576 inhibitor in MDA-MB-231 cells. Conclusion: We found tsRNA-26576 was upregulated in breast cancer tissue, and it could promote the cell growth while inhibite cell apoptosis. Therefore, tsRNA-26576 might serve as a potential clinical therapy target and a predictive marker for breast cancer.

Effects of row direction and row spacing on maize leaf senescence.

To analyze three row orientations (south-north, east-west, southwestern 20°) and two row spacings ('65 + 65', '160 + 40'), we investigated the effect of row orientation and planting pattern on photosynthetic performance, physiological and biochemical indicators related to the aging of leaves. Results revealed that during maturity stage, in north-south and east-west, the initial fluorescence (Fo) at '65 + 65' were higher than those under'160 + 40'; the maximum quantum yield of PS2 photochemistry(ΦP0), basal quantum yield of non-photochemical processes in PS2(ΦN0)of the lower leaves and photosynthetic rate of the upper and ear leaves under'160 + 40'were higher than those under'65 + 65'. The polyphenoloxidase (POD) activities of leaves at different positions under '160 + 40' were higher than that under'65 + 65', while the malondialdehyde (MDA) content was lower. The photosynthesis rate, superoxide dismutase (SOD) and catalase (CAT) activity of leaves at different positions under southwestern 20° '160 + 40' were higher than others. Whilst MDA content '160 + 40' were lower. Therefore, in De Hui City, Jilin Province, southwestern 20° '160 + 40' delayed leaf senescence at the late stage of growth of maize, as well as the effect of increasing maize yield was most obvious.

Overexpression and mutation of ZNF384 is associated with favorable prognosis in breast cancer patients.

BACKGROUND: To search for genes with high sensitivity and to explore its application value related to clinical prognostic prediction, so as to provide important foundation for the preventive intervention, early diagnosis, treatment and prognosis evaluation for breast cancer. METHODS: Tissue samples from ten clinical breast cancer patients were collected to search for the common mutant genes among various samples, and to explore the enrichment degree of mutant genes at both disease and signaling pathway levels using the whole exome sequencing (WES). Subsequently, targets genes with changes in expression levels that showed high correlations with mutation were screened from the above common genes using The Cancer Genome Atlas (TCGA) database. On this basis, differences in the mutation and expression levels of the screened target genes between breast cancer tissues and para-carcinoma tissues, as well as their correlations with patient survival were analyzed using the gene expression and mutation data in TCGA database, together with the clinical information. Finally, the potential regulatory pathways and potential downstream targets of the target genes were predicted through gene set enrichment analysis (GSEA) using Multi-Experiment Matrix (MEM) software. RESULTS: A total of 23 common mutant genes were discovered from the tissue samples from ten breast cancer patients, which were mostly enriched in the cancer, PI3K/Akt and cAMP signaling pathways. Among these 23 genes, only the changes in the expression levels of ZNF384 and PDE4DIP had displayed over 15% consistency with mutation. Besides, it was discovered through TCGA database analysis that, the expression level of ZNF384 gene in breast cancer tissues with ZNF384 mutation was far higher than that in those with no ZNF384 mutation. Moreover, such gene mutation and high expression had shown significantly positive correlation with the patient survival (P<0.05). In addition, GSEA indicated that, tissues with high ZNF384 expression were associated with enrichments related to cell cycle signaling pathway and mitosis metaphase pathway, while this series of effects might be correlated with its regulation on the level and activity of its downstream gene CXCL14. CONCLUSIONS: ZNF384 mutation and up-regulated ZNF384 expression level in breast cancer tissues is significantly positively correlated with patient survival. Therefore, ZNF384 can serve as a molecular marker for the diagnosis and prognostic prediction of breast cancer as well as a potential therapeutic target.

Chronic obstructive sleep apnea promotes aortic remodeling in canines through miR-145/Smad3 signaling pathway.

Obstructive sleep apnea (OSA) is a causal pathogenetic factor of many cardiovascular diseases, however, its role in aortic diseases remains unknown. Therefore, this study was performed to explore the potential effects and pathophysiological mechanisms of chronic OSA on aortic remodeling in a canine model. After chronic OSA, the morphological changes of ascending aorta were characterized by thinner cells with pycnotic nuclei and swollen mitochondria, and obvious hyperplasia of collagenous fiber in the matrix. Both the apoptotic ratio and collagen volume fraction were significantly increased in ascending aorta of chronic OSA canines. Besides, aortic sympathetic nerve sprouting increased significantly in chronic OSA group. Meanwhile, protein expression of TGF-ß1, Smad3, collagenI, apoptosis-inducing factor (AIF), tyrosine hydroxylase (TH) and growth associated protein-43 (GAP43) was upregulated after chronic OSA. Additionally, chronic OSA also strikingly increased pro-inflammatory factors like tumor necrosis factor α (TNF-α), NOD-like receptor 3 (NLRP3), NF-κB-p65 and oxidative stress factors like xanthine oxidase (XOD), malondialdehyde (MDA) while declined superoxide dismutase (SOD) activity. Furthermore, suppressed miR-145 and subsequently increased Smad3 expression were found obviously in vascular smooth muscle cells (VSMCs) treated by hypoxia. Luciferase reporter assays confirmed that Smad3 was one of the targets of miR-145. In conclusion, OSA could exacerbate aortic remodeling by aortic fibrosis, apoptosis and sympathetic nerve sprouting. miR-145/Smad3 signaling pathway might promote aortic remodeling during OSA. These findings provide novel information of chronic OSA-induced vascular dysfunction.

Dietary fatty acids affect lipid metabolism and estrogen receptor expression in N-methyl-N-nitrosourea-induced rat mammary cancer model.

BACKGROUND: We hypothesized that dietary polyunsaturated fatty acids (PUFA) could affect the expression of serum fatty acid binding protein 5 (FABP5) and CD36 levels and also fatty acid synthase (FAS), and estrogen receptor (ER) expressions in breast cancer cells. METHODS: A rat mammary cancer model was induced by injection i.p., with 50 mg MNU/kg body weight. Low (13.8% energy) or high-fat (42.5% energy) diets composed mainly of n-6 or n-3 PUFAs originating either from linoleic acid or linolenic acid, respectively, were given for eight weeks. After sacrifice at week 8, serum FABP5 level was examined and immunostainings of CD36, FAS, and ER of breast cancer tissue were observed. RESULTS: By week 8, there was no statistical difference of tumor formation rate between each group. The level of serum FABP5 in the high n-3 group was significantly lower than the low n-6 and high n-6 groups. Immunohistochemistry results showed that there was a significant difference of CD36 expression between the low n-3 group and high n-6 group (p < 0.05). Although the high n-3 group had the most inhibition on FAS and ER expression, there was no statistical difference between each group. CONCLUSIONS: Our study showed that different dietary PUFAs may affect lipid metabolism in breast cancer tissues by altering the expression of FABP5, CD-36, FAS, and ER, which may change treatment response and even prognosis of breast cancer.

Effect of n-3 and n-6 polyunsaturated fatty acids on lipid metabolic genes and estrogen receptor expression in MCF-7 breast cancer cells.

BACKGROUND: To investigate the effect of different ratios of n-6/n-3 polyunsaturated fatty acids (PUFAs) on the expression of lipid metabolic genes and estrogen receptor (ER). METHODS: This study took place in the Department of Surgery, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China, between January 2012 and October 2013. MCF-7 breast cancer cells were cultured for 48 hours with different ratios of PUFAs. Cell proliferation capability was detected by MTT method. Lipid metabolic genes and estrogen receptor (ER) were detected by western blot. RESULTS: Compared with the control group, the single n-6 PUFA group had no effect on sterol-regulatory-element-bindingprotein (SREBP) and fatty acid synthase (FAS) expression, while other groups all inhibited their expressions. Single n-6 group and 2:1 n-6/n-3 group down-regulated the expression of peroxisome proliferator-activated receptor (PPARγ), while in the other groups it was up-regulated. Single n-3 and n-6 groups had no effect on ER expression, while the others all suppressed the ER expression. CONCLUSIONS: Different ratios of n-6/n-3 polyunsaturated fatty acids may suppress the ER expression of MCF-7 cells and the effect may be related to its effect on the expression of lipid metabolic genes.