The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis.

PURPOSE: This study sought to investigate the causal effects of circulating C-reactive protein (CRP) level on risk of asthma and its subtypes by two-sample Mendelian randomization (MR) analysis. METHODS: We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma, and obesity-related asthma as genetic variables via a genome-wide summary association study (GWAS). MR analysis mainly based on the inverse variance weighted (IVW) method was performed to infer the causal relationship between exposure and outcomes. Cochran's Q test and MR-Egger regression analysis were performed to determine respectively the heterogeneity and pleiotropy among instrumental variables (IVs), and leave-one-out analysis was conducted to determine the stability of the MR results. RESULTS: In our study, 42 SNPs were identified as IVs for MR analyses. According to the primary inference results by IVW methods, circulating CRP was demonstrated to be significantly associated with risk of asthma [odds ratio (OR): 1.046; 95% confidence interval (95% CI): 1.004-1.090; P = .030] and obesity-related asthma (OR: 1.072; 95% CI: 1.009-1.138; P = 0.025), whereas no distinct causality with allergic asthma was found (OR: 1.051; 95% CI: 0.994-1.112; P = .081). Sensitivity analyses indicated that there was no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite the presence of heterogeneity. CONCLUSION: The present study suggested that higher CRP might genetically predict an increased risk of developing asthma and obesity-related asthma, without causality with allergic asthma.

Astragalin flavonoid inhibits proliferation in human lung carcinoma cells mediated via induction of caspase-dependent intrinsic pathway, ROS production, cell migration and invasion inhibition and targeting JAK/STAT signalling pathway.

The aim of the current study was to investigate the anti-lung cancer effects of astragalin. Studies were also undertaken to evaluate its effects on apoptosis induction, ROS production, cellular migration and invasion and JAK/STAT3 signalling pathway. MTT assay was used to evaluate cell viability in NSCLC A549 cells after exposure to astragalin molecule. Apoptosis was investigated using AO/EB staining, comet assay and western blotting assay. Fluorescence microscopy was implemented to estimate ROS production. Cell migration and invasion were measured using transwell chambers assay. Effects of astragalin on JAK/STAT pathway were investigated using western blotting assay. Results showed astragalin molecule induced inhibition of proliferation in A549 cells in a dose-dependent fashion. Further, the antiproliferative effects were found to mediate via apoptosis as suggested by AO/EB staining and western blotting assay. Astragalin modulated the expressions of caspase-3, caspase-9, Bax, Bak, Cyt-c Bcl-2, XIAP and Bcl-xL. Astragalin induced DNA damage in A549 cells which too indicated apoptotic cell death. Astragalin molecule enhanced the production of ROS by A549 cells. It inhibited both cell migration and invasion of A549 cells in a concentration-dependent manner. Finally, astragalin drug was observed with remarkable potential of targeting JAK/STAT pathway in A549 NSCLC cells. These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed.

Progress in the study of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) reversing multidrug resistance.

Currently, multidrug resistance (MDR) is one of the major reasons for failure in clinical cancer chemotherapy. Overexpression of the ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which significantly increases the efflux of anticancer drugs from tumor cells, enhances MDR. In the past few decades, four generations of P-gp inhibitors have appeared. However, they are limited in clinical application due to their severe toxic side effects. As a P-gp inhibitor and carrier for loading chemotherapy agents, TPGS has received increasing attention due to its advantages and unique properties of reversing MDR. TPGS is an amphipathic agent that increases the solubility of most chemotherapy drugs and decreases severe side effects. In addition, TPGS is an excellent carrier with P-gp-inhibiting ability. In this review, we summarize the latest articles on TPGS-based nanodelivery systems to prevent MDR.

Redox-responsive hyaluronic acid-based nanoparticles for targeted photodynamic therapy/chemotherapy against breast cancer.

Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization, blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.

The correlation of long non-coding RNA NEAT1 and its targets microRNA (miR)-21, miR-124, and miR-125a with disease risk, severity, and inflammation of allergic rhinitis.

ABSTRACT: The present study aimed to investigate the correlation of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) with microRNA (miR)-21, miR-124, and miR-125a, and their associations with disease risk, severity, and inflammatory cytokines of allergic rhinitis (AR).Totally 70 AR patients and 70 non-atopic obstructive snoring patients (as controls) were recruited. Inferior turbinate mucosa samples were collected from all participants for lncRNA NEAT1, its targets (miR-21, miR-124, and miR-125a), interleukin (IL)-4, IL-6, IL-10, and IL-17 detection via reverse transcription quantitative polymerase chain reaction. Disease severity of AR patients was assessed using individual nasal symptom score (INSS) and total nasal symptom score (TNSS).LncRNA NEAT1 was upregulated, while miR-21, miR-124, and miR-125a were downregulated in AR patients compared with controls. Additionally, lncRNA NEAT1, miR-21, and miR-125a displayed good values in differentiating AR patients from controls, while miR-124 could only slightly differentiate AR patients from controls. In AR patients, lncRNA NEAT1 was negatively associated with miR-21 and miR-125a, but not miR-124. However, in controls, no correlation of lncRNA NEAT1 with miR-21, miR-124, or miR-125a was observed. Furthermore, in AR patients, lncRNA NEAT1 was positively, while miR-21 and miR-125a was negatively associated with INSS (rhinorrhea, itching, congestion scores), TNSS and inflammatory cytokines; however, correlation of miR-124 with INSS, TNSS, and inflammatory cytokines was slight.LncRNA NEAT1 and its targets (miR-21 and miR-125a) present close correlations with disease risk, severity, and inflammation of AR, suggesting their potential as biomarkers for AR assessment.

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma.

Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

Chondroitin sulfate-based nanoparticles for enhanced chemo-photodynamic therapy overcoming multidrug resistance and lung metastasis of breast cancer.

As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.

Incidence, treatment, and survival analysis in mediastinal malignant teratoma population.

BACKGROUND: Mediastinal malignant teratoma, as a germ cell tumor, is rare and lacking of population-based study. This study aims to illustrate the incidence, treatment and prognosis of mediastinal malignant teratoma by using a population-based database. METHODS: We gathered clinicopathological data (1975-2016) of malignant teratoma from the Surveillance, Epidemiology and End Results (SEER) database. Then we conducted analysis on the incidence, treatment and prognosis of mediastinal malignant teratoma and other malignant teratomas. RESULTS: A total of 5,550 cases were in our study cohort, including mediastinal malignant teratoma (n=133) and other malignant teratomas (n=5,417). The incidence of mediastinal malignant teratoma in 2016 was 0.004 per 100,000 persons. Both overall survival (OS) and cancer-specific survival (CSS) of mediastinal malignant teratoma were significantly worse than those of other malignant teratomas (both P<0.001). Surgery significantly improved OS and CSS of either early-staged or all-staged patients with mediastinal malignant teratoma (all P<0.001). However, both chemotherapy and radiotherapy negatively influenced both OS and CSS of patients with mediastinal malignant teratomas (all P<0.001). Besides, compared with surgery alone, combinational therapies like surgery + chemotherapy or surgery + radiotherapy were more harmful to OS and CSS (all P<0.001) of patients with mediastinal malignant teratoma. CONCLUSIONS: Our population-based evidence showed that mediastinal malignant teratoma, a rare cancer, had worse prognosis compared with other malignant teratomas. Compared with chemotherapy and radiotherapy, surgery could yield more survival benefits for either early-staged or all-staged patients with mediastinal malignant teratoma. Adjuvant use of chemotherapy/radiotherapy to surgery cannot improve but potentially harm patient prognosis.

Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs.

The selective infiltration of cell membranes and tissue barriers often blocks the entry of most active molecules. This natural defense mechanism prevents the invasion of exogenous substances and limits the therapeutic value of most available molecules. Therefore, it is particularly important to find appropriate ways of membrane translocation and therapeutic agent delivery to its target site. Cell penetrating peptides (CPPs) are a group of short peptides harnessed in this condition, possessing a significant capacity for membrane transduction and could be exploited to transfer various biologically active cargoes into the cells. Since their discovery, CPPs have been employed for delivery of a wide variety of therapeutic molecules to treat various disorders including cranial nerve involvement, ocular inflammation, myocardial ischemia, dermatosis and cancer. The promising results of CPPs-derived therapeutics in various tumor models demonstrated a potential and worthwhile scope of CPPs in chemotherapy. This review describes the detailed description of CPPs and CPPs-assisted molecular delivery against various tissues and organs disorders. An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.

[Effects of potassium humate on ginger root growth and its active oxygen metabolism].

A pool-culture experiment was conducted to study the effects of potassium humate on the growth and active oxygen metabolism of ginger root. The results showed that applying potassium humate increased the root fresh mass and root vigor significantly, and promoted the root growth especially in later period. Potassium humate application obviously increased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), decreased the content of MDA, and delayed the senescence of ginger root. After applying potassium humate, the soluble protein content in root was increased by 49.18%, 25.89% and 13.26%, and the yield was increased by 61.29%, 48.13% and 9.92%, respectively, compared with the treatments CK, same application rate of humic acid, and same application rate of potassium monoxide.