Diagnostic and prognostic value of circular RNA CDR1as/ciRS‐7 for solid tumours: A systematic review and meta‐analysis

The circular RNA, CDR1as/ciRS‐7, functions as a vital regulator in various cancers; however, the predictive value of CDR1as remains controversial. Therefore, a comprehensive analysis for clarifying the precise diagnostic and prognostic value of CDR1as in solid tumours is needed. A literature review of several databases was conducted for identifying potential studies. Pooled odds ratios (ORs) and hazard ratios (HRs) were used for evaluating the diagnostic accuracy variables and survival. Overall, 15 studies (1787 patients) and 11 studies (1578 patients) were included for diagnostic and prognostic outcome syntheses, respectively. Up‐regulated CDR1as expression was found to be correlated with worse clinicopathological characteristics, including the T status, N status, histological grade, TNM stage and distant metastasis. The synthesized sensitivity was 0.72 (95% confidence interval [CI], 0.65‐0.79), and the specificity was 0.80 (95% CI, 0.74‐0.86). The positive likelihood ratio (LR), negative LR and diagnostic odds ratio (DOR) were 3.70, 0.34 and 10.80, respectively. The area under the receiver operator characteristic curve was 0.84 (95% CI, 0.80‐0.87). In the pooled prognostic analysis, patients with high CDR1as expression had worse overall survival (HR = 2.40, P < 0.001) and disease‐free survival (HR = 1.74, P < 0.001). These results suggest that CDR1as is a reliable diagnostic and prognostic biomarker with high accuracy and efficiency, which may potentially facilitate clinical decisions on solid tumours in the future.     

Dynamics of NK,CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID‐19

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Few studies have focused on the changes of NK, T‐ and B‐cell subsets, inflammatory cytokines and virus‐specific antibodies in patients with moderate COVID‐19. A total of 11 RT‐PCR‐confirmed convalescent patients with COVID‐19 and 11 patients with non‐SARS‐CoV‐2 pneumonia (control patients) were enrolled in this study. NK, CD8⁺ T, CD4⁺ T, Tfh‐like and B‐cell subsets were analysed using flow cytometry. Cytokines and SARS‐CoV‐2‐specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID‐19 than in control patients (P = 0.017). Effector memory CD8⁺ T‐cell counts significantly increased in patients with COVID‐19 during a convalescent period of 1 week (P = 0.041). TIM‐3⁺ Tfh‐like cell and CD226⁺ Tfh‐like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS⁺ Tfh‐like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS‐CoV‐2. The increase in effector memory CD8⁺ T‐cell counts, the up‐regulation of inhibitory molecules and the down‐regulation of active molecules on CD4⁺ T cells and Tfh‐like cells in patients with COVID‐19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID‐19.     

Metabolic phenotyping to monitor chronic enteritis canceration

Introduction

Untargeted metabolomics intends to objectively analyze a wide variety of compounds. Their diverse physicochemical properties make it difficult to choose an appropriate reconstitution solvent after sample evaporation without influencing the chromatography or hamper column sorbent integrity.

Objectives

The study aimed to identify the most appropriate reconstitution solvent for blood plasma samples in terms of feature recovery, four endogenous compounds, and one selected internal standard.

Methods

We investigated several reconstitution solvent mixtures containing acetonitrile and methanol to resolve human plasma extract and evaluated them concerning the peak areas of tryptophan-d₅, glucose, creatinine, palmitic acid, and the phophatidylcholine PC(P-16:0/P-16:0), as well as the total feature count

Results

Results indicated that acetonitrile containing 30% methanol was best suited to match all tested criteria at least for human blood plasma samples.

Conclusion

Despite identifying the mixture of acetonitrile and methanol being suitable as solvent for human blood plasma extracts, we recommend to systematically test for an appropriate reconstitution solvent for each analyzed biomatrix.

     

Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c‐MYC axis in breast cancer

Breast cancer is the second leading death cause of cancer death for all women. Previous study suggested that Protein Kinase D3 (PRKD3) was involved in breast cancer progression. In addition, the protein level of PRKD3 in triple‐negative breast adenocarcinoma was higher than that in normal breast tissue. However, the oncogenic mechanisms of PRKD3 in breast cancer is not fully investigated. Multi‐omic data showed that ERK1/c‐MYC axis was identified as a major pivot in PRKD3‐mediated downstream pathways. Our study provided the evidence to support that the PRKD3/ERK1/c‐MYC pathway play an important role in breast cancer progression. We found that knocking out PRKD3 by performing CRISPR/Cas9 genome engineering technology suppressed phosphorylation of both ERK1 and c‐MYC but did not down‐regulate ERK1/2 expression or phosphorylation of ERK2. The inhibition of ERK1 and c‐MYC phosphorylation further led to the lower protein level of c‐MYC and then reduced the expression of the c‐MYC target genes in breast cancer cells. We also found that loss of PRKD3 reduced the rate of the cell proliferation in vitro and tumour growth in vivo, whereas ectopic (over)expression of PRKD3, ERK1 or c‐MYC in the PRKD3‐knockout breast cells reverse the suppression of the cell proliferation and tumour growth. Collectively, our data strongly suggested that PRKD3 likely promote the cell proliferation in the breast cancer cells by activating ERK1‐c‐MYC axis.     

Protective effect of Agrimonia pilosa polysaccharides on dexamethasone‐treated MC3T3‐E1 cells via Wnt/β‐Catenin pathway

A water‐soluble polysaccharide (APP‐AW) was isolated from Agrimonia pilosa and prepared to three sulphated derivatives (S1, S2 and S3). The results showed that pre‐treatment with APP‐AW, S1, S2 and S3 each at the concentration of 50 μg/mL for 48 hours was able to prevent cytotoxicity induced by 1 μmol/L dexamethasone (Dex) in MC3T3‐E1 cells via inhibition of apoptosis, which is in line with the findings in flow cytometry analysis. Meanwhile, the decreased ALP activity, collagen content, mineralization, BMP2, Runx2, OSX and OCN protein expression in DEX‐treated MC3T3‐E1 cells were reversed by the addition of APP‐AW, S1, S2 and S3. Moreover, APP‐AW, S1, S2 and S3 rescued DEX‐induced increase of Bax, cytochrome c and caspase‐3 and decrease of Bcl‐2, Wnt3, β‐catenin and c‐Myc protein expression in MC3T3‐E1 cells. Our findings suggest that pre‐treatment with APP‐AW, S1, S2 and S3 could significantly protect MC3T3‐E1 cells against Dex‐induced cell injury via inhibiting apoptosis and activating Wnt/β‐Catenin signalling pathway, thus application of these polysaccharides may be a promising alternative strategy for steroid‐induced avascular necrosis of the femoral head (SANFH) therapy.     

MiR‐155 promotes interleukin‐1β‐induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1‐mediated PI3K/Akt pathway

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression.     

Identification of a novel germline BRCA2 variant in a Chinese breast cancer family

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L).     

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe^−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe^−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe^−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.     

Accurate Control Multiple Active Sites of Carbonaceous Anode for High Performance Sodium Storage: Insights into Capacitive Contribution Mechanism

Heteroatom doping is widely recognized as an appealing strategy to break the capacitance limitation of carbonaceous materials toward sodium storage. However, the concrete effects, especially for heteroatomic phase transformation, during the sodium storage reaction remain a confusing topic. Here, a novel hypercrosslinked polymerization approach is demonstrated to fabricate pyrrole/thiophene hypercrosslinked microporous copolymer and further give porous carbonaceous materials with accurately regulated N/S dual doping corresponding to starting feeding ratios. Significantly, the N doping contributes to the conductivity and surface wettability, while the S doping is bridged to build stable active sites, which can be electrochemically converted into mercaptan anions via faraday reaction and further enhancing reversible capacities. Meanwhile, the abundant S doping can also conduce to the expanded interlayer spacing to shorten the ions diffusion distance, thus optimizing the reaction kinetic. As a result, the N_0.2S_0.8‐micro‐dominant porous carbon delivers the highest reversible capacity of 521 mAh g^?1 at 100 mA g^?1 and excellent cyclic stability over 2000 cycles at 2000 mA g^?1 with a capacity decay of 0.0145 mAh g^?1 per cycle. This work is anticipated to provide an in‐depth understanding of capacitance contribution and illuminate the heteroatomic phase transformation during sodium storage reactions for doping carbonaceous anodes.