Declined circular RNA mitofusin 2 constrains the deterioration of Wilms tumor via modulating microRNA-372-3p/transforming growth factor-ß receptor type 2 axis.

To explore the action and mechanism in which circular RNA (circRNA) mitofusin 2 (MFN2) repressed the malignant proliferation of Wilms tumor (WT) via modulating microRNA (miR)-372-3p/transforming growth factor-ß receptor type 2 (TGFBR2) axis. CircRNA MFN2 was distinctly elevated in the tissues and cells of WT patients, while miR-372-3p was silenced in the tissues and cells of WT. Test of TGFBR2, PCNA and Bax was implemented. Transfection with si-circRNA MFN2 or miR-372-3p-mimic restrained cancer cell advancement and the number of PCNA content was declined, while transfection with miR-372-3p-inhibitor was opposite, and PCNA content was augmented. MiR-372-3p-inhibitor turned around si-circRNA MFN2's therapeutic action after co-transfection with si-circRNA MFN2 + miR-372-3p-inhibitor. Ultimately, it was verified that circRNA MFN2 was negatively associated with miR-372-3p, which was negatively linked with TGFBR2, and circRNA MFN2 was positively associated with TGFBR2. To sum up, the results of this research illuminated circRNA MFN2 repressed WT's malignant proliferation via modulating miR-372-3p/TGFBR2 axis.

ENTPD1-AS1-miR-144-3p-mediated high expression of COL5A2 correlates with poor prognosis and macrophage infiltration in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. Abnormal expression of noncoding RNAs (ncRNAs) have been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). Competing endogenous RNA network plays an important regulatory role in GC. However, its specific regulatory mechanism has not been elucidated. AIM: To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC. METHODS: RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2, miRNA and lncRNA related to the prognosis of GC. Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2. StarBase was used to predict the interaction of miRNA-lncRNA or miRNA-mRNA in GC. The relationship between COL5A2, miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis. The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining. RESULTS: We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC. miR-144-3p was downregulated and correlated with the prognosis of GC. miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2. ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC. CONCLUSION: COL5A2 regulated by ENTPD1-AS1-miR-144-3p was associated with poor prognosis and macrophage infiltration in GC. This could be a new biomarker and therapeutic target in GC.

Case report: A case of ocular infection caused by Corynespora cassiicola.

Objective: The aim of this study is to identify the pathogen causing ocular infection in a Chinese patient and to describe its morphological characteristics. Methods: Samples from the patient's intraoperative pus were collected for microscopic examination and culture. Morphology and drug sensitivities of the isolated fungus were analyzed. Ribosomal DNA (rDNA) sequencing was performed and blasted in GenBank. Results: A strain of fungi was repeatedly isolated from pus samples in different types of medium. No conidia were shown when the isolate cultured on normal PDA medium, whereas pseudoseptate thick-walled conidia were shown when cultured on medium containing leaf leachate. The results of BLAST and phylogenetic trees based on internal transcribed spacer, beta-tubulin, translation elongation factor 1-alpha, and RNA polymerase II gene demonstrated that the isolated fungus was Corynespora cassiicola. Minimum inhibitory concentration results of this organism were as follows: anidulafungin, 0.06 µg/ml; amphotericin B, 0.12 µg/ml; micafungin, 0.06 µg/ml; caspofungin, 0.5 µg/ml; 5-fluorocytosine, >64 µg/ml; posaconazole, 2 µg/ml; voriconazole, 0.25 µg/ml; itraconazole, 0.5 µg/ml; fluconazole, 64 µg/ml. Conclusion: The case was infected with Corynespora cassiicola and led to eye suppurative endophthalmitis and blindness. Combined applications of morphological and molecular biology techniques facilitate accurate diagnosis of fungal infections.

Efficacy and Safety of Non-Steroidal Mineralocorticoid Receptor Antagonists in Patients With Chronic Kidney Disease and Type 2 Diabetes: A Systematic Review Incorporating an Indirect Comparisons Meta-Analysis.

Background: The non-steroidal mineralocorticoid receptor antagonists (MRAs) are promising treatments in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We conducted a meta-analysis to explore the efficacy and safety of the non-steroidal MRAs (finerenone, apararenone, esaxerenone) and detect the differences among them. Methods: We searched several databases for eligible randomized controlled trials (RCTs) investigating non-steroidal MRAs versus placebo in patients with CKD and T2D. We performed a conventional meta-analysis separately, and then indirect comparisons for efficacy and safety outcomes were conducted among these included drugs. Results: Eight RCTs with 14,450 subjects were enrolled. In patients with CKD and T2D, a greater reduction in urinary albumin-to-creatinine ratio (UACR) (WMD -0.40, 95% CI -0.48 to -0.32, p < 0.001), estimated glomerular filtration rate (eGFR) (WMD -2.69, 95% CI -4.47 to -0.91, p = 0.003), systolic blood pressure (SBP) (WMD -4.84, 95% CI -5.96 to -3.72, p < 0.001) and a higher risk of hyperkalemia (RR 2.07, 95% CI 1.86 to 2.30, p < 0.001) were observed in the non-steroidal MRAs versus placebo; there is no significant difference in the incidence of serious adverse events between two groups (RR 1.32, 95% CI 0.98 to 1.79, p = 0.067). Compared with finerenone, esaxerenone showed no significant difference in UACR reduction (WMD 0.24, 95% CI -0.016 to 0.496, p = 0.869); apararenone and esaxerenone showed greater decreases in SBP (WMD 1.37, 95% CI 0.456 to 2.284, p = 0.010; WMD 3.11, 95% CI 0.544 to 5,676, p = 0.021). Conclusions: Despite the moderate increased risk of hyperkalemia, use of non-steroidal MRAs could reduce proteinuria and SBP in patients with CKD and T2D. In terms of renoprotection, esaxerenone and finerenone may have similar effects. Esaxerenone and apararenone may have better antihypertensive effects than finerenone. The head-to-head RCTs are still needed to compare the differences of the efficacy and safety in these non-steroidal MRAs.

Preparation and optimization of poly (lactic-co-glycolic acid) rod-shaped particles in nano size range for paclitaxel delivery.

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel.

Association between ICS use and risk of hyperglycemia in COPD patients: systematic review and meta-analysis.

BACKGROUND: The effect of inhaled corticosteroids (ICS) on risk of hyperglycemia in patients with chronic obstructive pulmonary disease (COPD) remains ambiguous. The aim of this study is to evaluate the association between ICS use and the incidence of hyperglycemia related adverse effects in COPD patients. METHODS: Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception to 25 May 2020. Randomized controlled trials (RCTs) of ICS versus control (non-ICS) treatment for COPD patients reporting on risk of hyperglycemia were included. The Mantel-Haenszel method with fixed-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Seventeen RCTs with 43,430 subjects were included in the meta-analysis. Pooled results suggested that there was no statistically significant difference in the risk of hyperglycemia between the ICS group and the control group (RR 1.02, 95% CI 0.90-1.16, P = 0.76). In addition, no significant difference was noted in the effect on glucose level (RR 1.20, 95% CI 0.79-1.82, P = 0.40), risk of diabetes progression (RR 0.84, 95% CI 0.20-3.51, P = 0.81) and new onset diabetes mellitus (RR 1.0, 95% CI 0.88-1.15, P = 0.95) between the ICS group and the control group. These findings also were consistent across all subgroup analyses. CONCLUSIONS: Use of ICS does not have an effect on the blood glucose and is not associated with the risk of new onset diabetes mellitus and diabetes progression in patients with COPD. Further RCTs exploring the association between ICS use and risk of hyperglycemia in COPD patients are still needed to verify our results of this analysis.

Efficacy and Safety of Different Doses of Systemic Corticosteroids in COPD Exacerbation.

BACKGROUND: Although systemic corticosteroids (SCS) have long been used to treat patients with COPD exacerbation, the recommended dose remains controversial. We aimed to perform a meta-analysis and an indirect treatment comparison to investigate the efficacy and safety of different doses of SCS in subjects with COPD exacerbation. METHODS: Studies were identified by searching different databases for randomized controlled trials that investigated the efficacy and safety of SCS with placebo in subjects with exacerbation of COPD. The different doses of SCS were assigned to low-dose (ie, initial dose ≤ 40 mg prednisone equivalent/d [PE/d]), medium-dose (initial dose = 40-100 mg PE/d, and high-dose (initial dose > 100 mg PE/d) groups. The indirect treatment comparison was performed between low-, medium-, and high-dose SCS groups. RESULTS: Twelve trials with 1,375 participates were included. Compared to placebo, the risk of treatment failure was lower in the low-dose SCS groups (risk ratio 0.61 [95% CI 0.43-0.88], P = .007) and high-dose SCS groups (risk ratio 0.64 [95% CI 0.48-0.85], P = .002); the FEV1 was significantly improved in low-dose (mean difference 0.09 [95% CI 0.06-0.12], P < .001), medium-dose (mean difference 0.23 [95% CI 0.02-0.44], P = .036), and high-dose SCS groups (mean difference 0.09, [95% CI 0.03-0.15], P < .001, respectively). Regarding safety, the incidence of hyperglycemia was higher in high-dose SCS groups versus placebo (risk ratio 2.52 [95% CI 1.13-5.62], P = .02). The indirect comparison between low-, medium-, and high-dose SCS found that the risk of treatment failure and changes in FEV1 were similar between these doses of SCS. CONCLUSIONS: This meta-analysis indicates that low-dose SCS (initial dose ≤ 40 mg PE/d) was sufficient and safer for treating subjects with COPD exacerbation, and it was noninferior to higher doses of SCS (initial dose > 40 mg PE/d) in improving FEV1 and reducing the risk of treatment failure. However, our findings need to be verified in head-to-head randomized controlled trials.

Alterations of Glucose Uptake and Protein Expression Related to the Insulin Signaling Pathway in the Brain of Phenobarbital-Addictive Rats by 18F-FDG PET/CT and Proteomic Analysis.

Drug addiction is a chronic relapsing brain disease. Alterations of glucose uptake and metabolism are found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Here, we established a rat model of phenobarbital addiction by 90 days of dose escalation and evaluated addiction-related symptoms. We also performed 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to detect glucose uptake in the brain and proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) on days 60 and 90 of phenobarbital or 0.5% carboxymethyl cellulose sodium (CMC-Na) (vehicle) administration. The results showed that phenobarbital-addictive rats developed severe withdrawal symptoms after abstinence and glucose uptake was significantly increased in the brain. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration, among which CALM1, ARAF, and Cbl proteins (related to the insulin signaling pathway) were significantly downregulated on day 60 but not day 90. However, SLC27A3 and NF-κB1 proteins (related to insulin resistance) were significantly upregulated on day 90 (data are available via ProteomeXchange with identifier PXD021101). Our data indicate that the insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury, so the findings may have important clinical implications.