Lanreotide-conjugated PEG-DSPE micelles: an efficient nanocarrier targeting to somatostatin receptor positive tumors

Lanreotide is an octapeptide analog of endogenous somatostatin, specifically binding with tumors over-express somatostatin receptor 2 (SSTR2). In this study, we conjugated lanreotide to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-(ethylene glycol))-2000] (PEG-DSPE), constructed active targeted micelles (lanreotide-PM), characterized their in vitro and in vivo targeting effect, and explored the receptor mediated transportion. The uptake of lanreotide-PM was found to be related to the expression level of SSTR2 in different cell lines and the competitive inhibition phenomenon indicated that the cellular uptake of lanreotide-PM was via a receptor meditated mechanism. In vivo, more lanreotide-PM accumulated in SSTR2 high expression tumor xenografts, endocytosed by the tumor cells, induced more apoptosis of tumor cells, and suppressed tumor growth efficiently. In conclusion, lanreotide–modified micelles containing antitumor drugs provide a promising strategy for the treatment of SSTR-expressing tumors.     

Effectiveness and safety of Yufeng Ningxin for the treatment of essential hypertension: A protocol for systematic review and meta-analysis

Background:Essential hypertension is the primary cause of death and disability and it has become a major public health problem globally. Yufeng Ningxin (YFNX) is a commonly used Chinese patent medicine in treating essential hypertension. The objective of this protocol is to evaluate the effectiveness and safety of YFNX for the treatment of essential hypertension.Methods:Randomized controlled trials (RCTs) in relation to the effectiveness and safety of YFNX in the treatment of essential hypertension will be systematically searched and collected from the following databases: PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database from the database inception to January 1, 2021. The data screening and extraction will be carried out by 2 different reviewers. The quality of randomized controlled trials will be assessed based on the version 2 of the risk-of-bias tool for randomized trials (RoB 2) in the Cochrane Handbook. The reduction of systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be served as the primary outcome. The secondary outcomes will include average SBP and average DBP during the day and the night measured by 24 hours ambulatory blood pressure monitoring, the clinical effectiveness rate, scores of traditional Chinese medicine syndrome, clinical symptoms, the quality of life and adverse events. Statistical analysis will be conducted with Review Manager 5.3 and STATA 14.0 software.Conclusion:This systematic review will provide strong evidence to assess the effectiveness and safety of YFNX in the treatment of essential hypertension.Trial registration number:INPLASY202110059.     

A five-gene signature for predicting overall survival of esophagus adenocarcinoma

Esophageal adenocarcinoma (EAC) is common and aggressive with increasing trend of incidence. Urgent need for an effective signature to assess EAC prognosis and facilitate tailored treatment is required.Differentially expressed mRNAs (DEMs) were identified by analyzing EAC tissues and adjacent normal samples from The Cancer Genome Atlas (TCGA). Then univariate regression analyses were performed to confirm prognostic DEMs. We used least absolute shrinkage and selection operator (LASSO) to build a prognostic mRNA signature whose performance was assessed by Kaplan–Meier curve, receiver operating characteristic (ROC). GSE72874 were used as an external test set. The performances of the signature were also validated in internal TCGA and external test sets. Gene set enrichment analysis (GSEA) and tumor immunity analysis were performed to decipher the biological mechanisms of the signature.A 5-mRNA signature consisted of SLC26A9, SINHCAF, MICB, KRT19, and MT1X was developed to predict prognosis of EAC. The 5-mRNA signature was promising as a biomarker for predicting 3-year survival rate of EAC in the internal test set, the entire TCGA set, and the external test set with areas under the curve (AUC) = 0.849, 0.924, and 0.747, respectively. Patients were divided into low- and high-risk groups based on risk scores of the signature. The high-risk group was mainly associated with cancer-related pathways and low levels of B cell infiltration.The 5-mRNA prognostic signature we identified can reliably predict prognosis and facilitate individualized treatment decisions for EAC patients.     

A randomized controlled trial protocol of the cardiovascular safety and efficacy of liraglutide in the treatment of type 2 diabetes

Background:Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.Methods:This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m² body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.Conclusions:For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.Trial registration:This study protocol was registered in Research Registry (researchregistry6306).     

Impact of binocular integrated visual field defects on healthy related quality of life in glaucoma

To investigate the impact of different types of binocular integrated visual field defects on the quality of life in glaucoma.Ninety-six patients with primary glaucoma were divided into 5 groups with 25, 24, 11, 15, and 21 patients according to types of the binocular integrated visual field (BVF) defects. The criteria for BVF grouping included mild visual field defect in binocular eyes, mild visual field defect in 1 eye and moderate or advanced defect in the other, moderate and non-overlapping visual field defect in both eyes, overlapping and moderate visual field defect in binocular eyes, and severe defect in both eyes, respectively. The visual field (VF) evaluation was based on H-P-A visual field grading system. Visual acuity, visual field tests and Glaucoma Quality of Life-15 Questionnaire (GQL-15) were performed for enrolled patients, and binocular visual field results were integrated. The changes and correlations of the Visual field index values and quality of life scores were compared among the 5 groups. The main factors affecting the quality of life in glaucoma were analyzed by multiple regression analysis.The best binocular integrated visual field index (BVFI) and optimal quality of life were observed in group A. The BVFI of group B was better than that of group C or group D, but the peripheral vision glare and dark adaptation were worse. No significant difference was noted between group C and group D in terms of BVFI. However, the glare and dark adaptation in group C were better than that in group D. The BVFI was the lowest and the quality of life was the worst in group E. In all, BVFI and decibels (dB) values were negatively correlated with GQL-15 scores and positively correlated with patients’ quality of life.Binocular integrated visual field accurately reflects the visual function in glaucoma. Higher binocular integrated visual field indices represent a better quality of life for patients with glaucoma. Mild to moderate synchronous or complementary binocular VF defects had a slight effect on the quality of life, while severe and non-compensated VF loss significantly impacts on quality of life in glaucoma patients.     

The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats

Aim:

Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia.

Methods:

SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting.

Results:

Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α.

Conclusion:

Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury.     

Absence of Toxemia in Clostridioides difficile Infection: Results from Ultrasensitive Toxin Assay of Serum

Digestive Diseases and Sciences - Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom...     

Inhibition of MicroRNA-302c on Stemness of Colon Cancer Stem Cells via the CARF/Wnt/β-Catenin Axis

Digestive Diseases and Sciences - Even though the relevance of microRNA (miR)-302c has been studied, little is known about its involvement in colon cancer (CC). Our aim here was to investigate the...