QAP14 suppresses breast cancer stemness and metastasis via activation of dopamine D1 receptor.

Breast cancer is the second leading cause of cancer-related mortality in women, mainly due to metastasis, which is strongly associated with cancer stemness. Our previous studies showed that the eradication of cancer stem-like cells (CSCs) may be related to the activation of dopamine D1 receptor (D1DR). This study aimed to explicitly demonstrate the target-role of D1DR activation in antimetastatic therapy and to investigate the potential efficacy and the underlying D1DR-related mechanisms of QAP14, a new oral compound. 4T1, MDA-MB-231, and D1DR-knockout 4T1 (4T1-D1DR) cells were selected for in vitro study, while 4T1 and 4T1-D1DR cells were further used to establish a mouse allograft model for in vivo study. Our results showed that D1DR is abundantly expressed in both 4T1 and MDA-MB-231 cells and that knocking out D1DR in 4T1 cells accelerated migration and invasion in vitro as well as lung metastasis in vivo. QAP14 inhibited colony formation, cell motility, mammosphere formation and CSC frequency, induced CSC apoptosis and D1DR expression, and increased cAMP/cGMP levels. Additionally, QAP14 showed inhibitory effects on tumor growth and lung metastasis with acceptable safety in vivo. Knocking out D1DR almost completely abolished the efficacy, confirming that QAP14 exhibits its anti-CSC and antimetastatic effects through D1DR activation. The underlying mechanisms involved suppression of the nuclear factor κB (NF-κB)/protein kinase B (Akt) pathway and consequent downregulation of both epithelial-to-mesenchymal transition (EMT) process and cancer stemness. In summary, our findings suggest a potential candidate compound, QAP14, as well as a potential target, D1DR, for metastatic breast cancer therapy.

Evaluation of Xpert GBS assay and Xpert GBS LB assay for detection of Streptococcus agalactiae.

BACKGROUND: Group B Streptococcal (GBS) infection is the primary agent of neonatal morbidity and mortality. Rapid and simple methods to detect GBS are Xpert GBS and GBS LB assays based on real-time polymerase chain reaction (PCR). However, since the diagnostic accuracy of the two techniques in diagnosing GBS remains unclear, we designed this study to appraise the diagnostic accuracy of the aforementioned. METHODS: A systematic search of all literature published before July 16, 2020 was conducted using Embase, PubMed, Web of Science, and Cochrane Library. The study quality was evaluated through Review Manager 5.3. Accordingly, data extracted in the included studies were analyzed using Meta-DiSc 1.4 and Stata 12.0 software. The diagnosis odds ratio (DOR) and bivariate boxplot were utilized to evaluate the heterogeneity. Publication bias was appraised by using Deeks' funnel plot. RESULTS: A total of 13 studies were adopted and only 19 sets of data met the criteria. The sensitivity and specificity of Xpert GBS were 0.91 (95% CI 0.89-0.92) and 0.93 (95% CI 0.92-0.94). The area under the curve (AUC) was 0.9806. The sensitivity and specificity results of Xpert GBS LB were 0.96 (95% CI 0.95-0.98) and 0.94 (95% CI 0.92-0.95), respectively. The AUC was 0.9950. No publication bias was found. CONCLUSIONS: The Xpert GBS and GBS LB assays are valuable alternative methods with high sensitivity and specificity. However, determining whether they can be used as clinical diagnostic standards for GBS is essential for the future.

Evaluation of GeneXpert vanA/vanB in the early diagnosis of vancomycin-resistant enterococci infection.

PURPOSE: Vancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we conducted a systematic review in the study. METHODS: Experimental data were extracted from publications until May 03 2021 related to the diagnostic accuracy of GeneXpert vanA/vanB for VRE in PubMed, Embase, Web of Science and the Cochrane Library. The accuracy of GeneXpert vanA/vanB for VRE was evaluated using summary receiver to operate characteristic curve, pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. RESULTS: 8 publications were divided into 3 groups according to two golden standard references, vanA and vanB group, vanA group, vanB group, including 6 researches, 5 researches and 5 researches, respectively. The pooled sensitivity and specificity of group vanA and vanB were 0.96 (95% CI, 0.93-0.98) and 0.90 (95% CI, 0.88-0.91) respectively. The DOR was 440.77 (95% CI, 37.92-5123.55). The pooled sensitivity and specificity of group vanA were 0.86 (95% CI, 0.81-0.90) and 0.99 (95% CI, 0.99-0.99) respectively, and those of group vanB were 0.85 (95% CI, 0.63-0.97) and 0.82 (95% CI, 0.80-0.83) respectively. CONCLUSION: GeneXpert vanA/vanB can diagnose VRE with high-accuracy and shows greater accuracy in diagnosing vanA.

Evaluation of Lateral-Flow Assay for Rapid Detection of Influenza Virus.

BACKGROUND: Influenza virus mainly causes acute respiratory infections in humans. However, the diagnosis of influenza is not accurate based on clinical evidence, as the symptoms of flu are similar to other respiratory virus. The lateral-flow assay is a rapid method to detect influenza virus. But the effectiveness of the technique in detecting flu viruses is unclear. Hence, a meta-analysis would be performed to evaluate the accuracy of LFA in detecting influenza virus. METHODS: Relevant literature was searched out in PubMed, Embase, Web of Science, and Cochrane Library databases with the keywords "lateral flow assay" and "flu virus". By Meta-DiSc software, pooled sensitivity, pooled specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (SROC), and area under the curve (AUC) can be calculated. RESULTS: This meta-analysis contains 13 studies and 24 data. The pooled sensitivity and specificity of the influenza virus detected by LFA were 0.84 (95% CI: 0.82-0.86) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled values of PLR, NLR, DOR, and SROC were 32.68 (17.16-62.24), 0.17 (0.13-0.24), 334.07 (144.27-773.53), and 0.9877. No publication bias was found. CONCLUSIONS: LFA exhibited high sensitivity and specificity in diagnosing influenza virus. It is a valuable alternative method which can diagnose influenza virus quickly. However, more evidence is required to confirm whether LFA is comparable to traditional methods for detecting the virus.