Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain.

Pulpitis is a common dental emergency that presents with intense pain; there is still no specific medicine to treat pulpitis-induced pain to date. Herein, differentially expressed genes in mouse anterior cingulate cortex (ACC) were investigated 7 days after pulp exposure via a combination of high-throughput transcriptomic and proteomic analyses. We screened 34 key genes associated with 8 critical pathways. Among these, genes (Elovl5, Ikbke, and Nbeal2) involved in immune or inflammatory responses exhibited exclusive regulation at the transcriptomic level, as confirmed by qRT-PCR. We also investigated the comprehensive expression profiles of genes (Erg1, Shank2, Bche, Serinf1, and Pax6) related to synaptic plasticity. Furthermore, the underlying mechanisms for pulpitis-induced pain through immune or inflammatory responses and synaptic plasticity were discussed. Taken together, our findings shed light on the mechanisms underlying pulpitis-induced pain, deepening our understanding of the molecular pathways and providing potential therapeutic and diagnostic targets.

Effect of steam explosion on the morphological, textural, and compositional characteristics of betel nut.

To reduce the adverse physical effects on the oral mucosa caused by excessive hardness of betel nut fibers, steam explosion was used to soften betel nuts. The effect of three operating parameters (pressure holding time, explosion pressure, and initial moisture content) on the morphology, texture, and chemical composition of the betel nuts was investigated. The fiber hardness and Shore hardness decreased by 56.17%-89.28% and 7.03%-34.29%, respectively, and the transverse tensile strength and fiber tensile strength also decreased by up to 60.72% and 24.62%, respectively. Moreover, the coefficient of static friction and moisture content increased. After steam explosion, the betel nut increased in transverse diameter, became darker and more yellow-red in color, and showed a damaged microstructure. The contents of free phenol and alkaloids decreased after steam explosion treatment, with free phenols and total alkaloids decreasing from 34.32 mg(GAE)/g and 7.84 mg/g to 21.58 mg(GAE)/g and 6.50 mg/g, respectively, after the A-50 s treatment condition. The steam explosion increased the quantity of phenols, alkaloids, and soluble solids released from the betel nut under the same simulated release conditions of the texture analyzer. The research also showed that increased pressure holding time and explosion pressure enhanced the explosion efficiency, while the initial moisture content was reduced the explosion efficiency. Therefore, steam explosion is an effective pretreatment approach to soften betel nut and facilitate healthy development of the betel nut industry.

Role of Xihuang capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions.

To investigate the impact of Xihuang Capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions. Totally 200 patients with stage III breast cancer were evenly randomized into control group (albumin-bound paclitaxel for chemotherapy) and observation group (Xihuang Capsules for adjuvant therapy based on the treatment of the control group). The RR and DCR of the observation group was markedly higher as compared to the control group (66.7% vs 28.6%; 80.9% VS 47.6%) (all P <0.05). After 4 weeks of treatment, the CD8+ in the two groups decreased, while CD3+ and CD4+ increased, and the change in observation group was more significant (all P<0.05). The observation group exhibited a better half-year, 1-year, 1.5-year and 2-year survival rates compared to the control group (81.0% vs 71.4%, 71.4% vs 57.1%, 57.1% vs 33.3% and 42.9%vs 19.0%) (all P<0.05). Adding Xihuang Capsule to adjuvant therapy with albumin paclitaxel chemotherapy benefits the patient's immunity and survival rate, with good efficacy and safety profiles.

Improved confidence estimation for the binomial proportion with applications to clinical studies.

In this paper, we establish a frequentist framework that incorporates all confidence sets with guaranteed frequentist coverage probability for the binomial proportion, where different confidence sets are completely characterized by their tail functions. Based on measures of precision in the form of interval length, probability of false coverage, and a new evaluation criterion utilizing prior information, we construct the optimal confidence set for the binomial proportion. The newly proposed methodology is applied to clinical studies. It is shown that confidence intervals obtained via the tail functions are often better than prevailing confidence intervals in view of precision.

A novel robust estimation for high-dimensional precision matrices.

In this paper we propose a new robust estimation of precision matrices for high-dimensional data when the number of variables is larger than the sample size. Different from the existing methods in literature, the proposed model combines the technique of modified Cholesky decomposition (MCD) with the robust generalized M-estimators. The MCD reparameterizes a precision matrix and transforms its estimation into solving a series of linear regressions, in which the commonly used robust techniques can be conveniently incorporated. Additionally, the proposed method adopts the model averaging idea to address the ordering issue in the MCD approach, resulting in an accurate estimation for precision matrices. Simulations and real data analysis are conducted to illustrate the merits of the proposed estimator.

Supplementation of dietary areca nut extract modulates the growth performance, cecal microbiota composition, and immune function in Wenchang chickens.

Introduction: The study was aimed at evaluating the effects of areca nut extract (ANE) on the growth performance, cecal microbiota, and immunity of Wenchang chickens. Methods: For this study, 42-day-old healthy Wenchang chickens (n = 450) with similar body weight were chosen. The animals were randomly divided into five groups, with six replicates per group and 15 chickens per replicate. One group was fed a basal diet (control; CCK). The remaining four groups were fed a basal diet supplemented with varying ANE concentrations: 0.038, 0.063, 0.100, and 0.151 g/kg, with the groups denoted as CNT1, CNT2, CNT3, and CNT4, respectively. The feeding experiment lasted 35 days. The ligated cecum segments of the control and experimental groups were collected for metabolomic and metagenomic analysis, while the bone marrow samples were extracted for tandem mass tag (TMT)-based proteomic analysis. Results: All the experimental groups exhibited significantly higher average daily gain (ADG) and significantly lower feed-to-weight (F/G) ratios than CCK. Metabolomic screening of the cecum contents revealed the presence of 544 differential metabolites, including several gut health-related metabolites, such as xanthine, hydroxy hypoxanthine, 2,5-dimethylhydrazine, ganoderic acid, and 2-aminohexanoic acid. Metagenomic analysis of the cecum contents showed an upregulation in the abundance of Prevotella spp. in the experimental groups. However, we observed no significant differences in the abundances of other cecal microbes at phylum and genus levels. Furthermore, we observed significant associations between Prevotella spp. and the differentially abundant metabolites, such as cherubins, thiaburimamide, and 3,4-dihydroxy-L-phenylalanine, (r)-mevalonate, 5-O-methylalloptaeroxylin, nalidixic acid, and deoxyloganin (p < 0.05). Proteomic analysis revealed that the differentially expressed proteins (such as interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), MHC-BF1, and death domain-associated protein (Daxx)) in the bone marrow of the chickens were primarily enriched in the immune network for IgA production and B cell receptor signaling pathway. Conclusion: In conclusion, dietary ANE supplementation was found to enhance metabolic activity and energy utilization, improve growth performance, modulate cecal microbiota, and strengthen the immunity of Wenchang chickens.

Dopamine Suppresses Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells via AKT/GSK-3ß/ß-Catenin Signaling Pathway.

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (Col1a1, Alp, Runx2, Opn, and Ocn). Furthermore, dopamine inactivated AKT/GSK-3ß/ß-catenin signaling pathway. Treatment of LiCl (GSK-3ß inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3ß/ß-catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis.

Neoadjuvant Chemotherapy Combined with Breast-Conserving Surgery in the Treatment of Triple-Negative Breast Cancer.

Objective: To study the clinical efficacy and quality of life of neoadjuvant chemotherapy combined with breast-conserving surgery in the treatment of triple-negative breast cancer. Methods: A retrospective analysis of 100 patients with triple-negative breast cancer was performed from May 2012 to April 2017. The patients were divided into an observation group and a control group according to different treatment methods, with 50 cases in each group. The control group received AC-T sequential chemotherapy after breast-conserving surgery, and the observation group received AC-T sequential chemotherapy before breast-conserving surgery (neoadjuvant). The operation time, postoperative immune function, postoperative tumor markers, postoperative efficacy, and postoperative complications of the two groups of patients were statistically analyzed, and the quality of life of the two groups of patients 1 year after the operation was compared. Results: Compared with the control group, the operation time and blood loss of the observation group were significantly reduced, and the difference was statistically significant (P < 0.05). The observation group produced significantly higher total effective rate after treatment (82.00% vs. 56.00%) (P < 0.05). The observation group exhibited superior immune function indexes CD3, CD4, and CD8 after operation when compared with the control group (P < 0.05). There was no significant difference in serum tumor marker levels between the two groups before surgery and after surgery (both P > 0.05). Three days after operation, the levels of procalcitonin (PCT) and TNF-α in the observation group were lower than those in the control group (P < 0.05). There was no significant difference in the local recurrence rate, distant metastasis rate, and 3-year survival rate between the two groups (P > 0.05); however, the postoperative complication rate of the observation group was 6.00%, which was significantly lower than that of the control group (30%) (P < 0.05). The overall health, physiological function, physiological function, and body pain of the observation group were significantly higher than those of the control group (P < 0.05). Conclusion: Neoadjuvant chemotherapy combined with breast-conserving surgery for triple-negative breast cancer can not only improve the therapeutic effect of patients and reduce the incidence of postoperative adverse reactions but also significantly improve the quality of life of patients after surgery.

Clinical Observation of Zhengyuan Capsule Combined with Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.

Objective: To study the clinical effect of Zhengyuan capsule combined with neoadjuvant chemotherapy in the treatment of triple-negative breast cancer (TNBC). Methods: From September 2014 to September 2017, 120 TNBC patients who underwent radical mastectomy in our hospital were randomly divided into control group (n = 60) and observation group (n = 60). The short-term curative effect, the incidence of toxicity and side effects, and the score of quality of life of the patients were compared. Both recurrence and metastasis rates were also analyzed. Results: The combined treatment of Zhengyuan capsule with neoadjuvant chemotherapy significantly improved the objective remission rate (70.00% in the observation group versus 40.00% in the control group) (P < 0.05). Moreover, this combined treatment significantly decreased the total incidence of side effects (35.00% versus 75.00%). Accordingly, the score of quality of life was also increased in patients treated with Zhengyuan capsule plus neoadjuvant chemotherapy (P < 0.05). Furthermore, supplementation of Zhengyuan capsule can significantly suppress both the recurrence and metastasis rate of TNBC in patients treated with neoadjuvant chemotherapy after radical mastectomy in following 3 years (30.00% versus 10.00%, P < 0.05). Conclusion: Zhengyuan capsule effectively improves the short-term curative effect, reduces the side effects of chemotherapy, and improves the quality of life of patients treated with neoadjuvant chemotherapy after radical mastectomy. More importantly, this combined treatment can also reduce the long-term recurrence and metastasis of TNBC.

Diagnostic Value of Echocardiography Combined with Serum h-FABP and cTnI in Myocardial Infarction and Its Evaluation Value in Left Ventricular Function.

Objective: To explore the value of color Doppler echocardiography (CDE) combined with serum heart-type fatty acid-binding protein (h-FABP) and cardiac troponin I (cTnI) in the diagnosis of myocardial infarction and its evaluation value in left ventricular function. Methods: A total of 44 patients with myocardial infarction who were treated in Cangzhou Central Hospital from October 2018 to February 2020 were included in the observation group, and 45 healthy subjects were included in the control group. The serum h-FABP and cTnI levels of the two groups were compared and analyzed. The coincidence rate of echocardiography plus serum h-FABP and cTnI for single diagnosis and combined diagnosis was analyzed. The left ventricular function indexes of patients with myocardial infarction in different cardiac function grades were compared, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac index (CI), and the ratio of peak velocity blood flow from left ventricular relaxation in early diastole to peak velocity flow in late diastole (E/A). The value of echocardiography combined with serum h-FABP and cTnI in the left ventricular function in patients with myocardial infarction was analyzed. Results: The levels of serum h-FABP and cTnI in the observation group were significantly higher than those in the control group (P < 0.05). CDE plus serum h-FABP and cTnI was associated with significantly higher sensitivity, specificity, and accuracy in diagnosing myocardial infarction versus single detection (P < 0.05). The LVEDV, SV, and CI parameters were similar in patients with different cardiac function grades (P > 0.05). Compared with cardiac function grades I and II, the level of LVEF in patients with myocardial infarction in grades III and IV of cardiac function decreased, while the levels of LVEDD, LVESD, LVESV, and E/A increased (P < 0.05). The levels of serum h-FABP and cTnI in patients with myocardial infarction increased with the increase of cardiac function grades (P < 0.05). Conclusion: Patients with myocardial infarction show high levels of h-FABP and cTnI, and CDE plus the detection of serum h-FABP and cTnI levels can significantly improve the detection accuracy and effectively evaluate the left ventricular function of patients with myocardial infarction, with a certain predictive value for cardiac function grading in myocardial infarction.

Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases.

Periodontitis is a chronic inflammatory and destructive disease caused by periodontal microbial infection and mediated by host immune response. As the main cause of loosening and loss of teeth in adults, it is considered to be one of the most common and serious oral diseases in the world. The co-existence of periodontitis and systemic chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, diabetes and so on is very common. It has been found that interleukin-17A (IL-17A) secreted by various innate and adaptive immune cells can activate a series of inflammatory cascade reactions, which mediates the occurrence and development of periodontitis and related systemic chronic inflammatory diseases. In this work, we review the role of IL-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases, and briefly discuss the therapeutic potential of cytokine targeted agents that modulate the IL-17A signaling. A deep understanding of the possible molecular mechanisms in the relationship between periodontitis and systemic diseases will help dentists and physicians update their clinical diagnosis and treatment ideas.

A Novel Functional Emulsifier Prepared with Modified Cassava Amylose with Octenyl Succinic Anhydride and Quercetin: Preparation and Application in the Pickering Emulsion.

An emulsifier with a targeted antioxidant effect was prepared using the inclusion complexes of octenyl succinic anhydride (OSA)-modified cassava amylose (CA) and quercetin (Q). The designed emulsifier, a carbohydrate polymer-flavonoid complex, exhibited both amphiphilic and antioxidant properties. To investigate the physical and oxidation stabilities of the prepared emulsion, three types of emulsions were prepared: primary emulsions stabilized by enzyme-modified starch, secondary emulsions stabilized by OSA-CA, and tertiary emulsions stabilized by Q-encapsulated complexes (OSA-CA/Q). The structural characteristics of CA, OSA-CA, and OSA-CA/Q were investigated by scanning electron microscopy, Fourier transform infrared spectrometry, and small-angle X-ray scattering analysis. The stabilities of the emulsions were evaluated based on their particle size distribution, zeta potential, creaming stability, and peroxide value. The results showed that the secondary and tertiary emulsions exhibited a relatively narrower particle size distribution than the primary emulsions, but the particle size distribution of the tertiary emulsions was the narrowest (10.42 µm). Moreover, the secondary and tertiary emulsions had lower delamination indices than the primary emulsions after 7 days of storage. The results obtained from the antioxidant experiments indicated that OSA-CA/Q exhibited good oxidation stability for application in emulsion systems.

Evaluation of left ventricular function in patients with heart failure after myocardial infarction by real-time three-dimensional transesophageal echocardiography.

OBJECTIVE: To evaluate the left ventricular function in patients with heart failure (HF) after myocardial infarction (MI) by real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) and explore its correlation with serum cTnI and H-FABP levels. METHODS: The data of 60 HF patients after MI from March 2019 to January 2021 were analyzed retrospectively and included in the research group. According to cardiac function grades, they were assigned to group A (20 cases), group B (20 cases), and group C (20 cases). During the same period, 50 healthy patients were included in the control group. The left atrial diameter (LAD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF) of participants were recorded and compared in the four groups. The serum levels H-FABP and cTnI were tested by ELISA. RESULTS: HF patients had poorer left heart structure and lower function and higher serum H-FABP and cTnI levels, as compared to the subjects in control group. Correlation analysis indicated that the cardiac function grade was positively correlated with LVEDV, LVESV, H-FABP, and cTnI, but negatively correlated with LVEF. The serum H-FABP and cTnI levels of HF patients were positively correlated with LVEDV and LVESV, but negatively correlated with LVEF. Logistic regression analysis revealed that cTnI and H-FABP were risk factors for HF, and LVEF was a protective factor for HF. CONCLUSION: Serum H-FABP and cTnI levels in HF patients are correlated with left ventricular function parameters, which presents a close relation to HF. RT-3D-TEE combined with the detection of serum H-FABP and cTnI yields important clinical significance for early diagnosis of HF.

A Cholesky-based sparse covariance estimation with an application to genes data.

The modified Cholesky decomposition (MCD) is a powerful tool for estimating a covariance matrix. The regularization can be conveniently imposed on the linear regressions to encourage the sparsity in the estimated covariance matrix to accommodate the high-dimensional data. In this paper, we propose a Cholesky-based sparse ensemble estimate for covariance matrix by averaging a set of Cholesky factor estimates obtained from multiple variable orderings used in the MCD. The sparse estimation is enabled by encouraging the sparsity in the Cholesky factor. The theoretical consistent property is established under some regular conditions. The merits of the proposed method are illustrated through simulation and a maize genes data set.

Establishment and Clinical Application of an Artificial Intelligence Diagnostic Platform for Identifying Rectal Cancer Tumor Budding.

Tumor budding is considered a sign of cancer cell activity and the first step of tumor metastasis. This study aimed to establish an automatic diagnostic platform for rectal cancer budding pathology by training a Faster region-based convolutional neural network (F-R-CNN) on the pathological images of rectal cancer budding. Postoperative pathological section images of 236 patients with rectal cancer from the Affiliated Hospital of Qingdao University, China, taken from January 2015 to January 2017 were used in the analysis. The tumor site was labeled in Label image software. The images of the learning set were trained using Faster R-CNN to establish an automatic diagnostic platform for tumor budding pathology analysis. The images of the test set were used to verify the learning outcome. The diagnostic platform was evaluated through the receiver operating characteristic (ROC) curve. Through training on pathological images of tumor budding, an automatic diagnostic platform for rectal cancer budding pathology was preliminarily established. The precision-recall curves were generated for the precision and recall of the nodule category in the training set. The area under the curve = 0.7414, which indicated that the training of Faster R-CNN was effective. The validation in the validation set yielded an area under the ROC curve of 0.88, indicating that the established artificial intelligence platform performed well at the pathological diagnosis of tumor budding. The established Faster R-CNN deep neural network platform for the pathological diagnosis of rectal cancer tumor budding can help pathologists make more efficient and accurate pathological diagnoses.

Periodontal disease and emotional disorders: A meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the relationship of periodontal disease with depression and anxiety via a systematic review and meta-analysis. METHOD: We systematically searched the EMBASE, PubMed, Web of Science, PsycINFO, and SinoMed databases (until August 4, 2019) with language restricted to English and Chinese. Case-control, cross-sectional, and cohort studies that calculated the risk ratio (RR), odds ratio (OR)/prevalence OR (POR), and hazard ratio (HR) of depression/anxiety with periodontal disease or the OR/POR/RR/HR of periodontal disease caused by depression/anxiety were included. Observational studies that reported the depression/anxiety scale score of patients with periodontal disease and healthy periodontal subjects aged ≥14 years were also included. We used the standard format to extract the following information from each included study: author/s, survey year, study design, age of participants, periodontal disease definition, depression/anxiety measurement, and summary of results. The Newcastle-Ottawa scale was used to ascertain the quality of the included citations. RESULTS: After screening, 40 studies were included. A meta-analysis of the case-control studies showed that periodontal disease was positively associated with depression (OR = 1.70, 95% confidence interval [CI] â€Š= 1.01-2.83). A meta-analysis of 12 studies showed that periodontal disease was significantly correlated with anxiety (OR = 1.36, 95% CI = 1.11-1.66). A meta-analysis of 18 studies showed that subjects with periodontal disease had higher depression scale score (standardized mean difference [SMD] = 1.05, 95% CI = 0.68-1.41) and anxiety scale score (SMD = 0.70, 95% CI = 0.44-0.96). CONCLUSION: Periodontal disease is associated with emotional disorders. However, the high degree of heterogeneity among studies should be considered. More high-quality prospective studies are required to confirm the relationship.

Bayesian auxiliary variable model for birth records data with qualitative and quantitative responses.

Many applications involve data with qualitative and quantitative responses. When there is an association between the two responses, a joint model will produce improved results than fitting them separately. In this paper, a Bayesian method is proposed to jointly model such data. The joint model links the qualitative and quantitative responses and can assess their dependency strength via a latent variable. The posterior distributions of parameters are obtained through an efficient MCMC sampling algorithm. The simulation is conducted to show that the proposed method improves the prediction capacity for both responses. Further, the proposed joint model is applied to the birth records data acquired by the Virginia Department of Health for studying the mutual dependence between preterm birth of infants and their birth weights.

LncRNA-SNHG7 Enhances Chemotherapy Resistance and Cell Viability of Breast Cancer Cells by Regulating miR-186.

BACKGROUND: Clinical tolerance to trastuzumab greatly affects the therapeutic effect in breast cancer (BC). Long-chain non-coding RNA (lncRNA) plays an important role in the development of trastuzumab resistance, in which SNHG7 can promote the epithelial mesenchymal transformation (EMT) of breast cancer cells into, while EMT is related to trastuzumab resistance of breast cancer cells. OBJECTIVE: To investigate whether lncRNA-SNHG7 can enhance chemotherapy resistance and cell viability of BC cells by regulating miR-186. METHODS: SK-BR-3 and SNHG7 of HER2+BC cells were induced to enhance the resistance of BC cells to trastuzumab by regulating miR-186, and to regulate the expression levels of SNHG7 and miR-186. The sensitivity of drug-resistant cells to trastuzumab and the changes of cell proliferation, migration, apoptosis, and EMT were measured and verified by tumorigenesis in vivo. The effects of miR-186 on SNHG7 were investigated through rescue experiments; the regulatory relationship between the expression of SNHG7 and miR-186 was verified by the double luciferase reporter (DLR) and the mechanism of SNHG7 was explored. RESULTS: Down-regulation of SNHG7 or up-regulation of miR-186 could increase the sensitivity of BC cells to trastuzumab, inhibit the proliferation, migration and EMT, and promote apoptosis. Compared with the down-regulation of SNHG7 or miR-186 alone, simultaneous down-regulation of SNHG7 and miR-186 on drug-resistant cells brought notably lower sensitivity to trastuzumab and apoptosis rate, and higher proliferation and apoptosis ability. The DLR showed that miR-186 could specifically inhibit the expression of SNHG7. The results of tumorigenesis in vivo revealed that down-regulation of SNHG7 or up-regulation of miR-186 could improve the therapeutic effect of trastuzumab and reduce the tumor volume, and miR-186 could also antagonize the effect of SNHG7. CONCLUSION: Down-regulation of SNHG7-targeted miR-186 can reverse trastuzumab resistance of BC cells, inhibit the proliferation, migration, and EMT levels of BC cells, and promote apoptosis.

ABCC9, NKAPL, and TMEM132C are potential diagnostic and prognostic markers in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The aim of this study is to identify the diagnostic and poor prognostic signatures in TNBC by exploring the aberrant DNA methylation and gene expression. Differential expression and methylation analysis of the TNBC and paracancer samples from The Cancer Genome Atlas were performed. Gene set enrichment and protein-protein interaction (PPI) network analysis was used to explore the mechanisms of TNBC. Methylation-gene expression correlation analysis was performed, and multivariate Cox analysis and receiver operating characteristics analysis were used to further screen the hub genes for TNBC. We identified 1,525 differentially expressed genes and 150 differentially methylated genes between TNBC and paracancer samples. About 96.64% of the methylation sites were located on the CpG island. A total of 17 Gene Ontology biological process terms and 18 signal pathways were significantly enriched. GNG4, GNG11, PENK, MAOA, and AOX1 were identified as the core genes of the PPI network. Methylation-expression correlations revealed that ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) showed promise as diagnostic and prognostic markers in TNBC. ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) were potential diagnostic and prognostic markers in TNBC.

Pluronic P123 modified nano micelles loaded with doxorubicin enhanced tumor-suppressing effect on drug-resistant breast cancer cells.

OBJECTIVE: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells. RESULTS: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1. CONCLUSIONS: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms. METHODS: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.