Increased ACSL6 Expression Predicts a Favorable Prognosis in Triple-negative Breast Cancer.

BACKGROUND: Long-chain acyl-coenzyme A synthases (ACSLs) are responsible for the catalysis of fatty acids into their corresponding fatty acyl-CoAs. The dysregulation of ACSLs has been increasingly recognized in cancer patients. However, the function of ACSL6 in triple-negative breast cancer (TNBC) is still completely unknown. METHODS: In this study, immunohistochemistry was applied to detect ACSL6 protein expression using a TNBC tissue microarray. Additionally, the mRNA levels of ACSL6 in human normal tissues and pancancer tissues were analyzed using Genotype Tissue Expression (GTEx) datasets and The Cancer Genome Atlas (TCGA) database. The correlations between the levels of ACSL6 expression and clinical characteristics were analyzed. The survival analysis of ACSL6 in TNBC was carried out using the Kaplan‒Meier Plotter online tool. Associations of ACSL6 with immune infiltration analyses were conducted using the ESTIMATE, CIBERSORT, and TISIDB databases. The relationship between ACSL6 and sensitivity to drugs was analyzed from Genomics of Drug Sensitivity in Cancer (GDSC). RESULTS: The results indicated a significant increase in ACSL6 expression in TNBC tissues compared to adjacent normal tissues. However, high ACSL6 expression was significantly associated with favorable survival outcomes in TNBC patients. Enrichment analysis revealed that coexpressed genes of ACSL6 were significantly enriched in various immunity processes. ACSL6 was positively correlated with the infiltration of memory CD4 T cells, while a negative correlation was found between ACSL6 and M2 macrophages and resting dendritic cells. Further analysis revealed that high levels of ACSL6 correlated with increased survival outcomes in cancer patients who received immunotherapy. CONCLUSION: Altogether, the current findings highlight the potential value of ACSL6 as a diagnostic and prognostic marker in the treatment of TNBC.

Recognition of outer membrane proteins using multiple feature fusion.

Introduction: Outer membrane proteins are crucial in maintaining the structural stability and permeability of the outer membrane. Outer membrane proteins exhibit several functions such as antigenicity and strong immunogenicity, which have potential applications in clinical diagnosis and disease prevention. However, wet experiments for studying OMPs are time and capital-intensive, thereby necessitating the use of computational methods for their identification. Methods: In this study, we developed a computational model to predict outer membrane proteins. The non-redundant dataset consists of a positive set of 208 outer membrane proteins and a negative set of 876 non-outer membrane proteins. In this study, we employed the pseudo amino acid composition method to extract feature vectors and subsequently utilized the support vector machine for prediction. Results and Discussion: In the Jackknife cross-validation, the overall accuracy and the area under receiver operating characteristic curve were observed to be 93.19% and 0.966, respectively. These results demonstrate that our model can produce accurate predictions, and could serve as a valuable guide for experimental research on outer membrane proteins.

Efficacy and Clinical Significance of the Zuogui Pill on Premature Ovarian Failure via the GDF-9/Smad2 Pathway.

Our study aims to investigate the efficacy and clinical significance of the Zuogui pill (ZGP) on premature ovarian failure (POF) via the GDF-9/Smad2 pathway. Changes in clinical symptoms in the control group (treated with Femoston alone) and the treatment group (treated with ZGP combined with Femoston) were assessed before and after treatment. Sex hormone levels, serum inflammatory cytokine levels, and ultrasound parameters were measured before and after treatment. POF rat models were established using cyclophosphamide and the POF rats were treated with Femoston, or ZGP combined with Femoston. GDF-9 and Smad2 expression levels were determined by RT-qPCR. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), interleukin (IL)-6, and IL-21 levels, and the pulsatility index (PI) and resistance index (RI) values were decreased, while the estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), mean ovarian diameter (MOD), and peak systolic velocity (PSV) values were increased in the treatment group compared to the control group. After treatment with ZGP combined with Femoston, GDF-9 and Smad2 expression in the ovarian tissues of POF rats increased. ZGP has a therapeutic effect on POF via modulation of the GDF-9/Smad2 pathway.

Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker.

Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer. Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The "survival" and "GSVA" package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model. Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared. Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer.

The single-atom iron nanozyme mimicking peroxidase remodels energy metabolism and tumor immune landscape for synergistic chemodynamic therapy and photothermal therapy of triple-negative breast cancer.

Chemotherapy, as one main strategy to relieve tumor progression, has a weak effect on triple-negative breast cancer (TNBC) chest wall metastasis. The development of near-infrared (NIR) light-responsive nanomaterials for chemodynamic therapy (CDT) and photothermal therapy (PTT) is a promising platform but still challenging in biomedicine. This study reports a peroxidase mimicking nanozyme (Fe-N-C SAzyme) against TNBC by CDT and PTT. Fe-N-C SAzyme generated reactive oxygen species (ROS) by decomposing H2O2 into hydroxyl radicals (•OH) and also induced light-to-heat conversion under the exposure of 808 nm laser irradiation. With these biological characteristics, the obtained Fe-N-C SAzymes displayed enhanced cell cytotoxicity and inhibition of cancer cell proliferation both in vitro and in vivo at a low dose of nanoagent and a moderate NIR laser power density. Besides, Fe-N-C nanoagent with its excellent ROS generation brought metabolic reprogramming of elevated glycolysis in tumor cells. In vivo experiments, when combined with PTT, the enhanced antitumor effect was found by the elimination of M-MDSC in tumor microenvironment. Fe-N-C SAzymes can serve as a new synergistic CDT and PTT nanoagent to simultaneously reprogram tumor metabolism and tumor microenvironment. It will provide prospects for chemodynamic/photothermal combined cancer therapy for TNBC chest wall metastasis based on the use of a single nanosystem.

Machine learning models based on immunological genes to predict the response to neoadjuvant therapy in breast cancer patients.

Breast cancer (BC) is the most common malignancy worldwide and neoadjuvant therapy (NAT) plays an important role in the treatment of patients with early BC. However, only a subset of BC patients can achieve pathological complete response (pCR) and benefit from NAT. It is therefore necessary to predict the responses to NAT. Although many models to predict the response to NAT based on gene expression determined by the microarray platform have been proposed, their applications in clinical practice are limited due to the data normalization methods during model building and the disadvantages of the microarray platform compared with the RNA-seq platform. In this study, we first reconfirmed the correlation between immune profiles and pCR in an RNA-seq dataset. Then, we employed multiple machine learning algorithms and a model stacking strategy to build an immunological gene based model (Ipredictor model) and an immunological gene and receptor status based model ICpredictor model) in the RNA-seq dataset. The areas under the receiver operator characteristic curves for the Ipredictor model and ICpredictor models were 0.745 and 0.769 in an independent external test set based on the RNA-seq platform, and were 0.716 and 0.752 in another independent external test set based on the microarray platform. Furthermore, we found that the predictive score of the Ipredictor model was correlated with immune microenvironment and genomic aberration markers. These results demonstrated that the models can accurately predict the response to NAT for BC patients and will contribute to individualized therapy.

Pituitary hormone α-MSH promotes tumor-induced myelopoiesis and immunosuppression.

The hypothalamic-pituitary (HP) unit can produce various hormones to regulate immune responses, and some of its downstream hormones or effectors are elevated in cancer patients. We show that the HP unit can promote myelopoiesis and immunosuppression to accelerate tumor growth. Subcutaneous implantation of tumors induced hypothalamus activation and pituitary α-melanocyte-stimulating hormone (α-MSH) production in mice. α-MSH acted on bone marrow progenitors to promote myelopoiesis, myeloid cell accumulation, immunosuppression, and tumor growth through its melanocortin receptor MC5R. MC5R peptide antagonist boosted antitumor immunity and anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. Serum α-MSH concentration was elevated and correlated with circulating myeloid-derived suppressor cells in cancer patients. Our results reveal a neuroendocrine pathway that suppresses tumor immunity and suggest MC5R as a potential target for cancer immunotherapy.

Analysis of lncRNA and mRNA Repertoires in Lung From BAFF-R-Deficient Pneumocystis-Infected Mice.

Background: Pneumocystis pneumonia (PCP) is a common medical issue in immunosuppressive patients. Increasing evidence supports that B cells may play an essential role in PCP individuals. The present study aims to integrate lncRNA and mRNA expression profiles and further investigate the molecular function of mature B cells in PCP. Methods: The lung tissue of wild-type (WT) mice and B-cell-activating factor receptor-deficient (mature B-cell deficiency, BAFF-R-/-) mice were harvested at 3 weeks after being infected with pneumocystis. After total RNAs were extracted, transcriptome profiling was performed following the Illumina HiSeq 3000 protocol. lncRNA-targeted miRNA pairs were predicted using the online databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment pathways were analyzed to functionally annotate these differentially expressed genes. Additionally, the immune-related lncRNA-miRNA-mRNA-ceRNA network was subsequently performed. The quantitative real-time PCR (RT-PCR) analysis was conducted to evaluate the lncRNA and mRNA expression profiles in WT-PCP mice and BAFF-R-/- PCP mice. Results: Compared with the control group, 166 mRNAs were observed to be aberrantly expressed (fold change value ≥2; P <0.05) in the BAFF-R-/- PCP group, including 39 upregulated and 127 downregulated genes, while there were 69 lncRNAs differently expressed in the BAFF-R-/- PCP group, including 15 upregulated and 54 downregulated genes. In addition, GO and KEGG pathway analyses showed that BAFF-R deficiency played an important role in the primary and adaptive immune responses in PCP. Furthermore, the lncRNA and mRNA co-expression network was established. We noted that the core network of lncRNA-TF (transcription factor) pairs could be classified into the categories including infection and immunity pathways. Conclusion: In summary, in this study, we further explored the role of mature B cells in the pathogenesis and progression of PCP and the data demonstrated that BAFF-R deficiency could play a significant role in immune regulation in the PCP population.

Value of CT Radiomics Combined with Clinical Features in the Diagnosis of Allergic Bronchopulmonary Aspergillosis.

Objective: Early diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and targeted treatment can block the process of the disease. This study explores the diagnostic value of CT radiomics combined with clinical features in allergic ABPA. Methods: A total of 40 patients with ABPA were studied retrospectively, divided into training set (n = 28) and test set (n = 12). Based on CT imaging, the radiomics features are extracted and combined with clinical features to build a diagnostic model. The diagnosis model was based on support vector machine algorithm. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic efficiency of the model. Results: There was no significant difference in general information and clinical data between the training and test sets (P > 0.05). The AUC of the training set and the test set is 0.896 (95% CI: 0.836-0.963) and 0.886 (95% CI: 0.821-0.952), respectively. Conclusion: Based on the CT radiomics model combined with clinical data, it has high efficiency in the diagnosis of ABPA.

A multifunctional α-Fe2O3@PEDOT core-shell nanoplatform for gene and photothermal combination anticancer therapy.

Exploration of versatile nanoplatforms within one single nanostructure for multidisciplinary treatment modalities, especially achieving a synergistic therapeutic efficacy of combinational gene/photothermal cancer therapy is still a great challenge in biomedicine and nanotechnology. In this study, a unique photothermal nanocarrier has successfully been designed and developed for a combination of gene therapy (GT) and photothermal therapy (PTT) of cancer cells. Surface-engineered iron oxides (α-Fe2O3) nanoparticles (NPs) with poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings are synthesized using a one-pot in situ oxidative polymerization method. The results show that the as-prepared α-Fe2O3@PEDOT core-shell NPs with a uniform particle size exhibit positively charged surfaces, facilitating efficient siRNA Bcl-2 (B-cell lymphoma-2) uptake for delivery to breast cancer cells. More importantly, α-Fe2O3@PEDOT core-shell NPs not only display good biocompatibility and water dispersibility but also strong optical absorption enhancement in the Vis-NIR region as compared to α-Fe2O3 NPs. The obtained α-Fe2O3@PEDOT core-shell NPs show an efficient photothermal conversion efficacy (η = 54.3%) and photostability under NIR laser irradiation. As a result, both in vitro and in vivo biological studies on two types of breast cancer cells/tumors treated with α-Fe2O3@PEDOT-siRNA nanocomplexes demonstrate high cancer cell apoptosis and tumor inhibition induced by synergistic GT/PTT therapy under mild conditions compared to an individual GT or PTT alone. Taken together, this is the first example of the use of an α-Fe2O3@PEDOT core-shell nanoagent as a siRNA delivery nanocarrier for highly effective gene/photothermal combination anticancer therapy.

TPMT mRNA Expression: A Novel Prognostic Biomarker for Patients with Colon Cancer by Bioinformatics Analysis.

BACKGROUND: To explore the clinicopathological significance and prognostic value of thiopurine methyltransferase (TPMT) in patients with colon cancer by bioinformatics analysis. MATERIALS AND METHODS: The clinicopathological information and TPMT expression data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Wilcoxon signed-rank test was used to evaluate the relationship between TPMT mRNA expression levels and clinicopathological characteristics in patients with colon cancer. Then, the prognostic value of TPMT mRNA expression for disease-free survival (DFS) and overall survival (OS) in patients with colon cancer was assessed by Kaplan-Meier and Cox regression analyses. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential functions of TPMT in patients with colon cancer. RESULTS: TPMT mRNA was significantly downregulated in colon cancer compared with normal tissues (P < 0.05). Wilcoxon analysis revealed that lower TPMT mRNA expression was remarkably associated with lymph node metastasis (P = 0.008), distant metastasis (P = 0.012) and advanced pathological stage (P = 0.010). Besides, the high TPMT mRNA level was also correlated with a favorable DFS and OS in colon cancer patients (both P < 0.05). Moreover, GO enrichment analysis indicated that the co-expressed genes of TPMT function as extracellular matrix (ECM) structural constituent, insulin-like growth factor binding, cell adhesion molecule binding and growth factor binding. KEGG enrichment analysis suggested that the co-expressed genes of TPMT were particularly enriched in amino sugar and nucleotide sugar metabolism, ECM-receptor interaction and focal adhesion. CONCLUSION: TPMT mRNA level might be a novel prognostic biomarker for patients with colon cancer.

Fis1 phosphorylation by Met promotes mitochondrial fission and hepatocellular carcinoma metastasis.

Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.

An artificial neural network model based on DNA damage response genes to predict outcomes of lower-grade glioma patients.

Although the prognosis of lower-grade glioma (LGG) patients is better than others, outcomes are highly heterogeneous. Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status can identify patient subsets with different prognosis. However, in the era of precision medicine, there is still a lack of biomarkers that can accurately predict the individual prognosis of each patient. In this study, we found that most DNA damage response (DDR) genes were aberrantly expressed in LGG patients and were associated with their prognosis. Consequently, we developed an artificial neural network (ANN) model based on DDR genes to predict outcomes of LGG glioma patients. Then, we validated the predictive ability in an independent external dataset and found that the concordance indexes and area under time-dependent receiver operating characteristic curves of the predict index (PI) calculated based on the model were superior to those of the mutation markers. Subgroup analyses demonstrated that the model could accurately identify patients with the same mutation status but different prognosis. Moreover, the model can also identify patients with favorable prognostic mutation status but poor prognosis or vice versa. Finally, we also found that the PI was associated with the mutation status and with the altered immune microenvironment. These results demonstrated that the ANN model can accurately predict outcomes of LGG patients and will contribute to individualized therapies. In addition, a web-based application program for the model was developed.

An autophagic gene-based signature to predict the survival of patients with low-grade gliomas.

BACKGROUND: Since autophagy remains an important topic of investigation, the RNA-sequence profiles of autophagy-related genes (ARGs) can provide insights into predicting low-grade gliomas (LGG) prognosis. METHODS: The RNA-seq profiles of autophagic genes and prognosis data of LGG were integrated from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model were carried out to identify the differentially expressed prognostic autophagy-related genes. Then, the autophagic-gene signature was formed and verified in TCGA test set and external CGGA cohorts. Time-dependent receiver operating characteristic (ROC) was examined to test the accuracy of this signature feature. A nomogram was conducted to meet the needs of clinicians. Sankey diagrams were performed to visualize the relationship between the multigene signatures and clinic-pathological features. RESULTS: Twenty-four ARGs were finally identified most relevant to LGG prognosis. According to the specific prediction index formula, the patients were classified into low-risk or high-risk groups. Prognostic accuracy was proved by time-dependent ROC analysis, with AUC 0.9, 0.93, and 0.876 at the survival time of 2-, 3-, and 5-year, respectively, which was superior to the AUC of the isocitrate dehydrogenase (IDH) mutation. The result was confirmed while validated in the TCGA test set and external validation CGGA cohort. A nomogram was constructed to meet individual needs. With a visualization approach, Sankey diagrams show the relationship of the histological type, IDH status, and predict index. In TCGA and CGGA cohorts, both low-risk groups displayed better survival rate in LGG while histological type and IDH status did not show consistency results. CONCLUSIONS: 24-ARGs may play crucial roles in the progression of LGG, and LGG patients were effectively divided into low-risk and high-risk groups according to prognostic prediction. Overall, our study will provide novel strategies for clinical applications.

PTEN inhibitor improves vascular remodeling and cardiac function after myocardial infarction through PI3k/Akt/VEGF signaling pathway.

BACKGROUND: Myocardial infarction (MI) is the leading cause of death from cardiovascular disease (CVD). Currently, the efficacy for MI treatment remains unsatisfactory. Therefore, it is urgent to develop a novel therapeutic strategy. METHODS: Left anterior descending arteries (LAD) of mice were ligated to induce MI. Another set of mice were intravenously injected with PTEN inhibitor BPV (1 mg/kg) 1 h after LAD ligation and continued to receive BPV injection daily for the following 6 days. Mice were performed echocardiography 14 days after surgery. RESULTS: Mice in MI group displayed an increased expression of PTEN with impaired cardiac function, enhanced cardiomyocyte apoptosis and decreased angiogenesis. BPV treatment significantly improved cardiac function, with reduced cardiomyocyte apoptosis, promoted angiogenesis, and activated PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway. CONCLUSION: PTEN inhibitor BPV could effectively prevent myocardial infarction in mice, highlighting its potential as a candidate therapeutic drug.

Combination of Fluorine-18 Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography (¹8F-FDG PET/CT) and Tumor Markers to Diagnose Lymph Node Metastasis in Non-Small Cell Lung Cancer (NSCLC): A Retrospective and Prospective Study.

BACKGROUND The early diagnosis of lymph node (LN) metastasis is crucial for patients with non-small cell lung cancer (NSCLC). However, the diagnosis of LN metastasis mainly dependent on ¹8F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography) which exhibited high false positive/negative rate. MATERIAL AND METHODS In retrospective analysis, 135 patients with NSCLC from February 2014 to March 2017 were enrolled. Based on the pathological examination, 71 patients were distributed to the LN Metastasis Group while 64 patients were distributed to the No LN Metastasis Group. Data from ¹8F-FDG PET/CT and tumor marker (TM) examination were collected to establish a logistic model. The receiver operating characteristic (ROC) curve analysis set the threshold of diagnostic factors. Finally, the diagnostic values of these factors were verified in a prospective analysis that included 78 patients with NSCLC from July 2017 to April 2019. RESULTS In our retrospective analysis, compared with the No LN Metastasis Group, the maximum standardized uptake value (SUVmax)/size of primary lesion, the CT value/SUVmax/short diameter of LN, the level of TM were all significantly different than the LN Metastasis Group (All P<0.05). Our logistic model showed that SUVmax of primary lesion (odds ratio [OR]=1.491), short diameter of LN (OR=1.310) and grade of TM (OR=2.927) were significant variables. The ROC curve analysis showed the specificity and sensitivity of our logistic model was 90.6% and 90.1%, respectively. In our prospective analysis, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the logistic model were calculated as 85.7%, 90.9%, 87.2%, 96.0%, and 71.4%, respectively. CONCLUSIONS Our study found that combining ¹8F-FDG PET/CT data and TM to establish a logistic model performed better in the diagnosis of LN metastasis with low false positive/negative rates in patients with NSCLC.

The efficacy and safety of PD-1/PD-L1 inhibitors in patients with recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

OBJECTIVES: There is currently no effective salvage therapeutic modality that improves the survival outcomes of patients with recurrent or metastatic nasopharyngeal carcinoma. However, the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors may provide clinical benefit for these advanced patients. MATERIALS AND METHODS: The databases, including PubMed, Web of Science, EMBASE and Cochrane Library, were systematically searched up to Nov 5, 2019. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) rate, overall survival (OS) rate, and drug-related adverse events were extracted and pooled meta-analyzed. RESULTS: From 71 search records, eight studies were included in the systematic review, of which three were eligible for final meta-analysis. In recurrent or metastatic nasopharyngeal carcinoma patients treated with anti-PD-1 therapy, the pooled ORR was 27% (95% confidence interval [CI] 19-36%), DCR was 63% (95% CI 50-75%), 6 months PFS rate was 49% (95% CI 40-58%), 1-year PFS rate was 25% (95% CI 19-32%), 1-year OS rate was 61% (95% CI 49-72%). The pooled incidences of any grade and grade ≥ 3 drug-related adverse events were 94% and 20% respectively. CONCLUSION: We present the aggregate response rates, survival rates and incidences of drug-related adverse events for recurrent or metastatic nasopharyngeal carcinoma patients receiving PD-1/PD-L1 blockage treatment, which could provide useful information for future design of clinical studies. There is a need for more randomized controlled studies with head-to-head comparison of PD-1/PD-L1 inhibitors and traditional chemotherapeutic strategies to enable better recommendations for optimal advanced nasopharyngeal carcinoma treatment.

Involvement of miR-200b-PKCα signalling in pulmonary hypertension in cor pulmonale model.

The right ventricle (RV) enlargement and pulmonary fibrosis are involved in cor pulmonale. The role of miR-200b in cor pulmonale is less well understood. This study was designed to evaluate the regulatory roles of miR-200b in cor pulmonale. Cor pulmonary mouse model was built via monocrotaline injection of monocrotaline (MCT). The expression of miR-200b in the lungs, RV and left ventricle (LV) are using real-time polymerase chain reaction. The transthoracic echocardiography was employed to determine the effects of miR-200b mimics and Gö6976 injection on MCT mice. The protein levels of protein kinase C α (PKCα), collagen, and fibronectin in the lung, RV, and LV in the mice with and without miR-200b mimics and Gö6976 injection were evaluated using western blot. The expression of miR-200b decreased in MCT mice, while there was no difference in LV. Both the miR-200b mimics and Gö6976 injection reversed the muscularization in the pulmonary artery, reversed RV hypertrophy, reduced RV systolic pressure, wall thickness and pulmonary fibrosis. The injection of miR-200b can reduce the PKCα expression in the lung, RV, and LV. This study confirmed the down-regulation of miR-200b in cor pulmonale. The reverse effects of miR-200b in the present study may provide a potential tool for cor pulmonary treatment.

IL-17 Inversely Correlated with IL-10 via the STAT3 Gene in Pneumocystis-Infected Mice.

BACKGROUND: Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated. METHODS: IL-10 and IL-17 levels in serum from PCP mice were detected via ELISA. The percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from IL-17-/- PCP mice and Th17 cells and IL-17+ γδT cells in IL-10-/- PCP mice were examined via flow cytometry. Also, antibody neutralization examination was also performed to elucidate the relationship of IL-17 and IL-10 in the PCP model. RESULTS: We noted the increase of IL-17 and IL-10 levels in serum from mice infected with Pneumocystis. Furthermore, deficiency of IL-17 or IL-10 could lead to the delayed clearance of Pneumocystis and more severed lung damage. Our data also demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. Interestingly, we also noted an increase of the IL-17 level in serum and Th17 cell and IL-17+ γδT cell percentages in the lung from IL-10-/- PCP mice. Using antibody neutralization experiments, we found that the STAT3 gene might play a critical role in the interplay of IL-17 and IL-10 in PCP. CONCLUSION: Taken together, our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3.

MiR-16-5p inhibits breast cancer by reducing AKT3 to restrain NF-κB pathway.

Background: Breast cancer endangers the life of women and has become the major cause of deaths among them. MiRNAs are found to exert a regulatory effect on the migration, proliferation and apoptosis of breast cancer cells. This research aims at investigating the miR-16-5p expression and its effect on the pathogenesis of breast cancer. Methods: Their clinical data were analyzed with qRT-PCR. CCK8, EdU and Transwell was performed to explore the function of miR-16-5p in cell migration and proliferation of breast cancer cells. Dual-luciferase reporter assay, immunohistochemistry and Western blotting were carried out to explore the relation between miR-16-5p and AKT3. Results: It was discovered that miR-16-5p was lowly expressed in breast cancer patients. Meanwhile, breast cancer patients with under-expressed miR-16-5p had a lower survival rate than those with highly expressed miR-16-5p. Furthermore, decreased miR-16-5p in cell and animal models enhanced migration and proliferation of breast cancer cells, stimulated cell cycle and reduced cell apoptosis. Finally, we found miR-16-5p restrained the NF-κB pathway and decreased AKT3 gene, thereby suppressing the breast cancer development. Conclusion: It can be seen that miR-16-5p exhibits a low expression in breast cancer tissues, which can inhibit breast cancer by restraining the NF-κB pathway and elevating reducing AKT3.