High expression level of CXCL1/GROα is linked to advanced stage and worse survival in uterine cervical cancer and facilitates tumor cell malignant processes.

BACKGROUND: CXCL1 belongs to a member of the ELR + CXC chemokine subgroups that also known as GRO-alpha. It has been recognized that several types of human cancers constitutively express CXCL1, which may serve as a crucial mediator involved in cancer development and metastasis via an autocrine and/or paracrine fashion. However, the expression pattern and clinical significance of CXCL1 in human uterine cervix cancer (UCC), as well as its roles and mechanisms in UCC tumor biology remains entirely unclear. METHODS: The expression and clinical significance of CXCL1 in UCC tissues was explored using immunohistochemistry and bioinformatics analyses. The expression and effects of CXCL1 in HeLa UCC cells were assessed using ELISA, CCK-8 and transwell assays. Western blotting experiments were performed to evaluate the potential mechanism of CXCL1 on malignant behaviors of HeLa UCC cells. RESULTS: The current study demonstrated that CXCL1 was expressed in HeLa UCC cells, PHM1-41 human immortalized cervical stromal cells, as well as cervical tissues, with UCC tissues having an evidently high level of CXCL1. This high level of CXCL1 in cancer tissues was notably related to poor clinical stages and worse survival probability, rather than tumor infiltration and patient age. In addition, CXCL1 expression was extremely correlated with CCL20, CXCL8 and CXCL3 cancer-associated chemokines expression. In vitro, the growth and migration abilities of HeLa cells were significantly enhanced in the presence of exogenous CXCL1. Gain-function assay revealed that CXCL1 overexpression significantly promoted growth and migration response in HeLa cells in both autocrine and paracrine manners. Finally, we found that CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes, and HeLa cell malignant behaviors derived from CXCL1 overexpression were further interrupted in the presence of the ERK1/2 blocker. CONCLUSION: Our findings demonstrate the potential roles of CXCL1 as a promoter and a novel understanding of the functional relationship between CXCL1 and the ERK signaling pathway in UCC.

Folate metabolic profiling and expression of folate metabolism-related genes during panicle development in foxtail millet (Setaria italica (L.) P. Beauv).

BACKGROUND: Foxtail millet grain has higher folate content than other cereal crops. However, the folate metabolite content and the expression patterns of folate metabolite-related genes are unknown. RESULTS: Liquid chromatography-mass spectrometry was used to investigate 12 folate metabolites in a foxtail millet panicle. The content of total folate and derivatives gradually decreased during panicle development. Polyglutamate 5-formyl-tetrahydrofolate was the major form. Twenty-eight genes involved in the folate metabolic pathway were identified through bioinformatic analysis. These genes in Setaria italica, S. viridis and Zea mays showed genomic collinearity. Phylogenetic analysis revealed that the folate-related genes were closely related among the C4 plants compared to C3 plants. The gene expressions were then studied at three panicle development stages. The gene expression patterns were classified into two groups, namely SiADCL1 and SiGGH as two key enzymes, which are responsible for folate synthesis and degradation; their expression levels were highest at the early panicle development stage, up to 179.11- and 163.88-fold, respectively. Their expression levels had a similar downward trend during panicle development and were significantly positively correlated with the concentration of total folate and folate derivatives. However, SiSHMT3 expression levels were significantly negatively correlated with total folate concentration. CONCLUSION: Besides being the major determinants of folate and folate derivatives accumulation, SiADCL1 and SiGGH expression levels are key limiting factors in the foxtail millet panicle. Therefore, SiADCL1 and SiGGH expression levels can be targeted in genetic modification studies to improve folate content in foxtail millet seeds in the future. © 2021 Society of Chemical Industry.

Survival outcomes of neoadjuvant chemotherapy-related strategies compared with concurrent chemoradiotherapy for locally advanced cervical cancer: a meta-analysis of randomized controlled trials.

PURPOSE: The survival benefits of neoadjuvant chemotherapy (NAC) compared with those of concurrent chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC) patients remain uncertain. Meta-analysis was used to compare NAC and CRT. METHODS: A systematic search was performed up to 9 September 2020. Survival outcomes were analyzed based on event frequency or hazard ratios (HRs). Multilevel mixed-effects logistic regression was applied to analyze the effect of regimen variables on survival outcomes. RESULTS: Analysis based on Cox regression showed that CRT was better than NAC + radical hysterectomy (RT) (HR 1.25; 95% confidence interval (CI)) 1.02-1.54; p = 0.034) in terms of overall survival (OS). According to multilevel mixed-effects model analysis comparing NAC + RT and CRT, LACC patients who used cisplatin instead of carboplatin had a better Progression-free survival (PFS) (odds ratio (OR) 1.54; 95% CI 1.08-2.20; p = 0.016). When NAC + CRT and CRT were compared, gemcitabine administration was associated with a decrease in PFS (OR 0.47; 95% CI 0.22-0.99; p = 0.047). Increased doses of cisplatin and paclitaxel were associated with survival improvement. CONCLUSION: Based on traditional meta-analysis, CRT was better than NAC + RT in terms of OS. Carboplatin instead of cisplatin as part of the NAC + RT strategy or gemcitabine use in NAC + CRT may not be a good choice. An increased total dosage of paclitaxel and/or cisplatin as part of NAC + CRT and CRT strategies may improve the survival outcome of LACC patients.

Food-Derived Pharmacological Modulators of the Nrf2/ARE Pathway: Their Role in the Treatment of Diseases.

Oxidative stress, which refers to unbalanced accumulation of reactive oxygen species (ROS) levels in cells, has been linked to acute and chronic diseases. Nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays a vital role in regulating cytoprotective genes and enzymes in response to oxidative stress. Therefore, pharmacological regulation of Nrf2/ARE pathway is an effective method to treat several diseases that are mainly characterized by oxidative stress and inflammation. Natural products that counteract oxidative stress by modulating Nrf2 have contributed significantly to disease treatment. In this review, we focus on bioactive compounds derived from food that are Nrf2/ARE pathway regulators and describe the molecular mechanisms for regulating Nrf2 to exert favorable effects in experimental models of diseases.

CXCL3 overexpression promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway.

CXCL3 belongs to the CXC-type chemokine family and is known to play a multifaceted role in various human malignancies. While its clinical significance and mechanisms of action in uterine cervical cancer (UCC) remain unclear. This investigation demonstrated that the UCC cell line HeLa expressed CXCL3, and strong expression of CXCL3 was detected in UCC tissues relative to nontumor tissues. In addition, CXCL3 expression was strongly correlated with CXCL5 expression in UCC tissues. In vitro, HeLa cells overexpressing CXCL3, HeLa cells treated with exogenous CXCL3 or treated with conditioned medium from WPMY cells overexpressing CXCL3, exhibited enhanced proliferation and migration activities. In agreement with these findings, CXCL3 overexpression was also associated with the generation of HeLa cell tumor xenografts in athymic nude mice. Subsequent mechanistic studies demonstrated that CXCL3 overexpressing influenced the expression of extracellular signal-regulated kinase (ERK) signaling pathway associated genes, including ERK1/2, Bcl-2, and Bax, whereas the CXCL3-induced proliferation and migration effects were attenuated by exogenous administration of the ERK1/2 blocker PD98059. The data of the current investigation support that CXCL3 appears to hold promise as a potential tumor marker and interference target for UCC.

MicroRNA-188 inhibits biological activity of lung cancer stem cells through targeting MDK and mediating the Hippo pathway.

NEW FINDINGS: What is the central question of this study? The aim was to investigate the function of microRNA-188 in the biological characteristics of lung cancer stem cells and the molecular mechanisms involved. What is the main finding and its importance? This study highlights a new molecular mechanism involving microRNA-188, MDK and the Hippo signalling pathway that plays a suppressive role in biological activity of lung cancer stem cells. This finding might offer new insights into gene-based therapy for lung cancer. ABSTRACT: MicroRNAs (miRNAs) have been implicated in lung cancer and reported as new promising diagnostic and therapeutic tools for cancer control. Here, we investigated the action of microRNA-188 (miR-188) in lung cancer stem cells. We first tested miR-188 expression in clinical samples of lung cancer patients, and a low expression profile of miR-188 was found. Next, we analysed the role of miR-188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we used a xenograft model to validate the capability of miR-188 in tumorigenesis. Overexpression of miR-188 reduced viability and metastasis of cancer stem cells. Similar results were reproduced in vivo, where overexpression of miR-188 retarded tumour growth in mice. We also identified MDK as a target of miR-188, and overexpression of MDK was found in lung cancer samples. Overexpressed MDK promoted the malignant behaviours of lung cancer stem cells. In addition, the Hippo pathway was found to be inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of the Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumours. To sum up, our results reveal that miR-188 inhibits the malignant behaviours of lung cancer stem cells and the growth of xenograft tumours. This study might offer new insights into gene-based therapies for cancer.

Comparison of clinical outcomes between intravascular ultrasound-guided and angiography-guided drug-eluting stent implantation: A meta-analysis of randomised control trials and systematic review.

This systematic review was designed to evaluate the overall efficacy of angiography-guided drug-eluting stent (DES) implantation vs intravascular ultrasound-guided (IVUS) implantation for percutaneous coronary intervention. The electronic databases CENTRAL, PubMed, Cochrane, and EMBASE were searched for systematic reviews to investigate angiography-guided and IVUS-guided DES implantation. We measured the following six parameters in each patient: cardiovascular death, stent thrombosis, target lesion revascularisation (TLR), myocardial infarction (MI), major adverse cardiac events (MACEs), and all-cause death. Twelve studies involving 6268 subjects were included, with 2984 receiving IVUS-guided DES implantation and 3284 using angiography-guided DES implantation. With regard to MACEs, TLR, MI, cardiovascular death, and all-cause death, the IVUS-guided DES implantation group had remarkably improved clinical outcomes. However, there was no significant statistical difference in stent thrombosis between the two groups. Dramatic decrease in MACEs through IVUS guidance was presented by trial sequential analysis. Remarkably improved clinical outcomes, including MACEs, cardiovascular death, all-cause death, and TLR, were identified through IVUS-guided DES implantation in comparison with angiography-guided DES implantation. Nonetheless, the effect on stent thrombosis and MI required further confirmation. In this meta-analysis, eligible randomised clinical trials were warranted to verify the findings and to determine the beneficial effect of IVUS guidance for patients.

Identification and Application of CLE Peptides for Drought Resistance in Solanaceae Crops.

The CLE (CLAVATA3/Embryo Surrounding Region-related) family, a group of peptides with hormone-like features, plays a pivotal role in plant growth, development, and adaptation to stress. Through homology-based blast analysis of 32 Arabidopsis thaliana CLE peptide sequences, we have identified 5, 14, and 10 CLE family members in Nicotiana tabacum, Capsicum annuum, and Solanum melongena, respectively. Chemical synthesis and functional assays of the peptides led to the discovery that NtCLE3 substantially enhances the drought resistance of these three Solanaceae crops. Our transcriptome, RT-qPCR, and antioxidant enzyme activity data showed that NtCLE3 increased antioxidant capacity and ABA synthesis in tobacco. Moreover, the recombinant protein RPNtCLE3, composed of 6*NtCLE3, preserved the capacity to foster drought resilience and proved to be a promising drought resistance regulator, which presents a more favorable alternative for field applications compared to ABA which degrades rapidly under sunlight exposure. This research unveils the prospective utility of NtCLE3 in enhancing drought tolerance in Solanaceae crops and provides new ideas for the development of novel bioregulators aimed at mitigating drought stress.

Disulfiram/Copper Induce Ferroptosis in Triple-Negative Breast Cancer Cell Line MDA-MB-231.

BACKGROUND: The complex formed by disulfiram (DSF) and copper (Cu) is safe and effective for the prevention and treatment of triple-negative breast cancer (TNBC). Although previous studies have shown that DSF/Cu induces ferroptosis, the mechanism remains unclear. METHODS: The mitochondrial morphology of TNBC treated with DSF/Cu was observed by transmission microscopy, and intracellular levels of iron, lipid reactive oxygen species (ROS), malondialdehyde, and glutathione were evaluated to detect the presence of ferroptosis. Target genes for the DSF/Cu-activated ferroptosis signaling pathway were examined by transcriptome sequencing analysis. Expression of the target gene, HOMX1, was detected by qRT-PCR, immunofluorescence and western blot. RESULTS: The mitochondria of TNBC cells were significantly atrophied following treatment with DSF/Cu for 24 h. Addition of DSF/Cu supplement resulted in significant up-regulation of intracellular iron, lipid ROS and malondialdehyde levels, and significant down-regulation of glutathione levels, all of which are important markers of ferroptosis. Transcriptome analysis confirmed that DSF/Cu activated the ferroptosis signaling pathway and up-regulated several ferroptosis target genes associated with redox regulation, especially heme oxygenase-1 (HMOX-1). Inhibition of ferroptosis by addition of the ROS scavenger N-acetyl-L-cysteine (NAC) significantly increased the viability of DSF/Cu-treated TNBC cells. CONCLUSIONS: These results show that DSF/Cu increases lipid peroxidation and causes a sharp increase in HMOX1 activity, thereby inducing TNBC cell death through ferroptosis. DSF/Cu is a promising therapeutic drug for TNBC and could lead to ferroptosis-mediated therapeutic strategies for human cancer.

The comparison of ibuprofen versus acetaminophen for blood pressure in preeclampsia: a meta-analysis of randomized controlled studies.

INTRODUCTION: The comparison of ibuprofen with acetaminophen for blood pressure (BP) in preeclampsia remains controversial. We conduct a systematic review and meta-analysis to compare the impact of ibuprofen versus acetaminophen on BP for preeclampsia. METHODS: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through October 2019 for randomized controlled trials (RCTs) assessing the effect of ibuprofen versus acetaminophen on BP for preeclampsia. This meta-analysis is performed using the random-effect model. RESULTS: Four RCTs are included in the meta-analysis. Overall in preeclampsia patients, ibuprofen and acetaminophen show similar systolic BP (SBP) (standard mean difference [SMD] = 0.04; 95% CI = -0.26-0.34; p= .81), diastolic BP (DBP) (SMD = 0.15; 95% CI = -0.18-0.48; p = 0.38), mean BP (MAP) (SMD = 0.02; 95% CI = -0.29-0.33; p = .91), severe range BP (SMD = -0.10; 95% CI = -0.40-0.19; p = .50), severe hypertension (SMD = 1.18; 95% CI = 0.85-1.62; p = .32), and satisfaction level (SMD = 1.2; 95% CI = 0.95-1.53; p = .13). CONCLUSIONS: Ibuprofen and acetaminophen may have no significant influence on BP for preeclampsia.

DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy.

Breast cancer has become a leading cause of cancer-related deaths in women worldwide. DNA methylation has been revealed to play an enormously important role in the development and progression of breast cancer. DNA methylation is regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT2, and DNMT3. DNMT3 family has three members: DNMT3A, DNMT3B, and DNMT3L. The roles and functions of DNMT1 in breast cancer have been well reviewed. In this article, the roles of DNMT3A and DNMT3B in breast tumorigenesis and development are reviewed. We also discuss the SNP and mutations of DNMT3A and DNMT3B in breast cancer. In addition, we summarize how DNMT3A and DNMT3B are regulated by non-coding RNAs and signaling pathways in breast cancer, and targeting the expression levels of DNMT3A and DNMT3B may be a promising therapeutic approach for breast cancer. This review will provide reference for further studies on the biological functions and molecular mechanisms of DNMT3A and DNMT3B in breast cancer.

Heterologous Expression of SiFBP, a Folate-Binding Protein from Foxtail Millet, Confers Increased Folate Content and Altered Amino Acid Profiles with Nutritional Potential to Arabidopsis.

The mechanism underlying folate degradation in foxtail millet grains remains unclear. Here, we identified SiFBP (Setaria italica folate-binding protein) from foxtail millet. A phylogenetic tree revealed that FBPs have close genetic relationships among cereal crop species. Docking analysis and heterologous expression of SiFBP in yeast showed that it could bind folic acid (FA). The SiFBP localized to the plasma membrane in tobacco mesophyll cells by transient expression. In Arabidopsis, it was expressed specifically in the roots and germinating seeds. Overexpressing SiFBP in yeast and Arabidopsis significantly increased folate contents. Untargeted metabolome analysis revealed differentially accumulated metabolites between the transgenic lines (TLs) and wild type (WT); these metabolites were mainly enriched in the amino acid metabolism pathway. The relative contents of lysine and leucine, threonine, and l-methionine were significantly higher in the TLs than in WT. Genes related to the folate and lysine synthesis pathways were upregulated in the TLs. Thus, SiFBP can be used for biofortification of folate and important amino acids in crops via genetic engineering.

Association between IL1B -511C/T polymorphism and Behçet's disease: a meta-analysis.

BACKGROUND: Many studies have investigated the relationship between the interleukin-1ß gene (IL1B) -511C/T polymorphism and the risk of Behçet's disease (BD); however, the conclusions remain controversial. METHODS: In this study, we systemically retrieved relevant studies from the Chinese Biomedicine Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed databases. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using the meta-package Stata version 12.0. RESULTS: The IL1B -511C/T polymorphism was not related to BD susceptibility using any of the tested models (C vs T: OR = 1.20, 95% CI = 0.97-1.49; CC vs TT: OR = 1.27, 95% CI = 0.95-1.70; CT vs TT: OR = 1.03, 95% CI = 0.781.36; dominant model: OR = 1.12, 95% CI = 0.87-1.46; recessive model: OR = 1.27, 95% CI = 0.89-1.82). Similarly, subgroup analysis including studies consistent with the Hardy-Weinberg equilibrium revealed no association between the IL1B polymorphism and BD susceptibility. CONCLUSION: This meta-analysis indicates that the IL1B -511C/T polymorphism is unlikely to affect the risk of BD; however, further large-scale, carefully designed studies are needed to verify these results.

Ovarian microcystic stromal tumor with omental metastasis: the first case report and literature review.

BACKGROUND: Microcystic stromal tumor (MCST) of the ovary is an extremely rare subtype of sex cord-stromal neoplasm first described by Irving and Young in 2009. Tumors from all previously reported cases (fewer than 40 total) were benign, but one was a case of ovarian MCST that reoccurred. CASE PRESENTATION: Herein, we present a unique single case of ovarian MCST with omental metastasis in a 47-year-old Chinese female along with its histologic and immunohistochemical profile and genetic alterations. The tumor exhibited the previously described classic microscopic features and immunoprofiles of MCST. The tumorlet in the omentum presented the same histological structures and characteristically expressed ß-catenin protein (localized in the nucleus). Molecular analysis identified a point mutation (c.98C > G) in exon 3 of CTNNB1. CONCLUSIONS: To the best of our knowledge, no such report has been documented for ovarian MCST with omental metastasis. The study may provide new insights into the tumor biology of MCST and provide a better understanding of this rare entity.

Inhibition of DNA Methyltransferase by RG108 Promotes Pluripotency-Related Character of Porcine Bone Marrow Mesenchymal Stem Cells.

Mesenchymal stem/stromal cells (MSCs) have been identified in almost all adult human tissues and been used in numerous clinical trials for a variety of diseases. Studies have shown that MSCs would undergo cellular senescence when cultured over a long term, which is brought on by increased epigenetic modifications, including DNA methylation. However, the mechanism of MSCs senescence is not well studied. In this study, the effects of RG108, a DNA methyltransferase inhibitor (DNMTi), on senescence, apoptosis, and pluripotency gene expressions in porcine bone marrow (pBM)-MSCs were investigated. First, we determined the optimized dose and time of RG108 treatment in pBM-MSCs to be 10 µM for 48 hours, respectively. Under these conditions, the pluripotency genes (NANOG, POU5F1), the anti-senescence genes (TERT, bFGF), and the anti-apoptosis gene (BCL2) were increased, whereas the apoptotic gene (BAX) was decreased. RG108 protected against apoptosis when pBM-MSC induces apoptosis with H2O2 for 1.5 hours. We also found that RG108 significantly induced the expression of NANOG and POU5F1 by decreasing DNA methylation in gene promoter regions. These results indicate that an optimized dose of RG108 may promote the pluripotency-related character of pBM-MSCs through improving cellular anti-senescence, anti-apoptosis, and pluripotency, which provide a better cell origin for stem cell therapy.

Aspirin Use and Mortality in Women With Ovarian Cancer: A Meta-Analysis.

BACKGROUND: Aspirin use has been suggested to reduce the incidence of ovarian cancer (OC) in women. However, previous studies regarding the association between aspirin use and mortality in women with OC showed inconsistent results. We aimed to evaluate the association between aspirin use and mortality in women with OC in a meta-analysis. METHODS: Relevant cohort studies were obtained via search of PubMed, Cochrane's Library, and Embase databases from inception to May 3, 2020. A random-effect model, which incorporates the potential heterogeneity among the included studies, was used to pool the results. Predefined stratified analyses were applied to evaluate the potential study characteristics on the outcome, including the timing of aspirin use, dose of aspirin, age of the women, and the clinical stages of the cancer. Sensitivity analysis by omitting one study at a time was used to assess the stability of the results. RESULTS: Six cohort studies including 17,981 women with OC were included. Pooled results showed that aspirin use had no statistically significant association with mortality in these patients (adjusted risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.70 to 1.02, p = 0.08; I2 = 69%). The results were similar for OC-specific mortality (RR: 0.85, 95% CI: 0.57 to 1.26, p = 0.41) and all-cause mortality (RR: 0.78, 95% CI: 0.55 to 1.11, p = 0.17). Stratified analyses suggested that aspirin use had no statistically significant association with mortality risk in OC regardless the timing of aspirin use, dose of aspirin, age of the women, or the clinical stages of the cancer. Funnel plots suggested potential risk of publication bias (p all > 0.05). However, further "trim-and-fill" analysis incorporating hypothesized unpolished studies to achieve symmetrical funnel plots showed similar results of the meta-analysis (RR: 0.91, 95% CI: 0.74 to 1.13, p = 0.39). CONCLUSIONS: Current evidence from observational studies indicated that aspirin use had no statistically significant association with mortality in women with OC.

A Decision-Making Supporting Prediction Method for Breast Cancer Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) may increase the resection rate of breast cancer and shows promising effects on patient prognosis. It has become a necessary treatment choice and is widely used in the clinical setting. Benefitting from the clinical information obtained during NAC treatment, computational methods can improve decision-making by evaluating and predicting treatment responses using a multidisciplinary approach, as there are no uniformly accepted protocols for all institutions for adopting different treatment regiments. In this study, 166 Chinese breast cancer cases were collected from patients who received NAC treatment at the First Bethune Hospital of Jilin University. The Miller-Payne grading system was used to evaluate the treatment response. Four machine learning multiple classifiers were constructed to predict the treatment response against the 26 features extracted from the patients' clinical data, including Random Forest (RF) model, Convolution Neural Network (CNN) model, Support Vector Machine (SVM) model, and Logistic Regression (LR) model, where the RF model achieved the best performance using our data. To allow a more general application, the models were reconstructed using only six selected features, and the RF model achieved the highest performance with 54.26% accuracy. This work can efficiently guide optimal treatment planning for breast cancer patients.

SERS studies on normal epithelial and cancer cells derived from clinical breast cancer specimens.

Surface-enhanced Raman scattering (SERS) spectroscopy of single-cell suspensions obtained from fresh specimens of breast cancer tissue and normal breast tissue by mechanical enzymatic digestion was obtained and analysed, which is different from most Raman studies using breast cancer cell lines. Random forest classification was implemented to develop effective diagnostic algorithms for the classification of SERS of different typed cells. We first examined the SERS spectra of the primary breast cancer single cell and normal epithelial single cell obtained by flow sorting cytometry due to their biomarkers of CD326+/CD45-. Comparison analyses on their SERS spectra disclose that the nucleic acid and protein levels of the primary breast cancer single cell are higher than those of the normal epithelial single cell, while the lipids are at a relatively lower level. An important finding is that the cholesterol, palmitic acid, and sphingomyelin in the cancer cell profiles exhibit stronger than those of normal cells, while the glycans are at a relatively lower level. Furthermore, the standard deviation (SD) of the normal epithelial single cell is larger than that of the breast cancer cell, and the SD of the primary breast cancer single cell is more obvious than that of the normal epithelial cells. In addition, the prospective application of an algorithm to the dataset results in an accuracy of 78.2%, a precision of 75.5%, and a recall of 66.7%. The breast cancer diagnostic model laid a solid foundation for judgment of breast-conserving surgical margins and early diagnosis of breast cancer.

Thioguanine Induces Apoptosis in Triple-Negative Breast Cancer by Regulating PI3K-AKT Pathway.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of biological targets and poor sensitivity to conventional therapies. Chemotherapy is the main clinical therapy, but the effective screening strategy for chemotherapy drugs is poorly investigated. Drug repositioning has been the center of attention in recent years attracting numerous studies. Here, we firstly found multiple common features between leukemia and TNBC by analyzing the global transcriptome profiles based on the transformed comparison data from NCI60. Therefore, we investigated the role of the classic leukemia drug thioguanine (6-TG) in TNBC cancer cells. Our results indicated that 6-TG inhibited cell proliferation and tumor cell progression by suppressing PI3K-AKT pathway via downregulating the DNA methylation level of PTEN. Moreover, apoptosis was induced via the activation of PI3K-AKT downstream TSC1 and the downregulation of methylation levels of DAXX, TNF, FADD and CASP8 etc. These findings indicated 6-TG exerts its anti-tumor effects in vitro and in vivo through regulating the DNA methylation levels of genes involved in PI3K-AKT and apoptosis pathway. Meanwhile, our study suggested that transcriptome-based drug screening has potential implications for breast cancer therapy and drug selection.

Sinus of Valsalva aneurysm protruding into the mitral anterior leaflet causing dyspnea: A CARE-compliant case report.

INTRODUCTION: Sinus of Valsalva aneurysm (SVA) protruding into the mitral anterior leaflet is an extremely rare clinical condition; herein, we present a case of unruptured noncoronary SVA protruding into the mitral anterior leaflet. PATIENT'S CONCERNS: A 46-year-old male was referred to hospital for exertional dyspnea. DIAGNOSIS: Transthoracic echocardiography (TTE) and coronary computed tomography angiography (CTA) suggested a noncoronary SVA protruding into the mitral anterior leaflet, causing mitral regurgitation and aortic insufficiency. INTERVENTIONS: The aneurysm was resected and the aortic and mitral valves were replaced with mechanical valves via a transaortic approach. OUTCOMES: Postoperative recovery was uneventful. CONCLUSIONS: A rare noncoronary SVA protruding into the mitral anterior leaflet can be diagnosed via TTE and CTA. Transaortic mitral surgery is feasible in patients with a dilated aortic annulus ring and mitral valve diseases.