British Journal of Biomedical Science最新文献

Introduction: To investigate the expression level of miR-206 in serum of patients with asymptomatic carotid artery stenosis (CAS) and estimate the value of miR-206 in the diagnosis and prognosis of asymptomatic CAS. Methods: A total of 206 individuals enrolled in this study, including 105 CAS patients and 101 controls. RT-qPCR technology was applied to measure the relative level of miR-206, and Pearson's correlation coefficient was performed to analyze the relationship between carotid artery stenosis degree and miR-206 level. An ROC curve was drawn to assess the diagnostic value of miR-206 in asymptomatic CAS. The 5-year prognosis of asymptomatic CAS patients was tested using multivariate Cox regression analysis and Kaplan-Meier survival curve. Results: MiR-206 expression was reduced in asymptomatic CAS patients. The AUC of the ROC curve of miR-206 was 0.939, with a sensitivity of 86.70% and a specificity of 86.14%. The amount of CAS gradually increased with the decrease of miR-206 level. Seven-teen patients in the low miR-206 expression group developed CIEs, and 3 patients in the high miR-206 expression group developed CIEs during the 5-year follow-up. miR-206 and the amount of CAS were independent factors for the occurrence of CIEs within 5 years in asymptomatic CAS patients. Conclusion: Serum miR-206 has high diagnostic accuracy for asymptomatic CAS and has predictive value for the incidence of CIEs in patients within 5 years.

Introduction: Leukopenia is one of the major side effects of myelosuppressive chemotherapy such as cyclophosphamide (CTX). We and others have used CTX either alone or in combination with G-CSF for the mobilization of hematopoietic stem cells (HSCs). This mobilization can induce expansion of myeloid cells with immunosuppressive phenotype. In this pilot study, we aimed to test whether bone marrow lysate (BML)/CTX, a rich source of growth factors, can lower the expansion of myeloid cells with immunosuppressive phenotypes in tumor-bearing mice without interfering with the anti-tumor effects of CTX or with the mobilization of HSCs. Methods: Female CD1 mice were treated on day 0 with an i.p. injection of Ehrlich ascites carcinoma (EAC). On day 7, the mice were i.p. injected with CTX followed by s.c. injection of G-CSF for 5 consecutive days, single s.c. injection of BML/PBS or BML/CTX or single i.v. injection of BMC/PBS or BMC/CTX. Results: Treatment of EAC-bearing mice with BML/PBS or BML/CTX did not interfere with the anti-tumor effect of CTX. EAC increased the numbers of immature polymorphonuclear cells (iPMN; neutrophils) in both blood and spleen. Treatment of EAC-bearing mice with CTX further increased the numbers of these cells, which were decreased upon treatment with BML/CTX. Treatment with BML/PBS or BML/CTX increased the numbers of stem cells (C.Kit⁺Sca^-1⁺) in BM; the effect of BML/CTX was higher, but with no significant effect on the numbers of HSCs. Future studies are needed to analyze the molecular components in BM lysate and to determine the underlying mechanisms.

Introduction: Long non-coding RNAs (lncRNAs) exhibit crucial roles in human tumors. However, the role of lncRNA CARD8-AS1 in lung adenocarcinoma remains elusive. This study investigated the role of CARD8-AS1 in lung adenocarcinoma. Materials and Methods: The expression of CARD8-AS1 was detected by RT-qPCR analysis and confirmed using an online database. The clinical value of CARD8-AS1 was evaluated using the Kaplan-Meier curve and multivariate Cox regression analyses. The effects of CARD8-AS1 on cancer cell proliferation, migration, and invasion potential were assessed through several cellular experiments. Western blot assay was used to measure Bcl-2 and Bax protein levels. The interaction among CARD8-AS1, miR-650, and Bax, was assessed using a dual-luciferase reporter assay. Results: The expression of CARD8-AS1 was decreased in lung adenocarcinoma tissues and cell lines (p < 0.001). Low expression of CARD8-AS1 was related to tumor size (p = 0.042), TNM stage (p = 0.021), lymph node metastasis (p = 0.025), and poor overall survival (p < 0.05). Elevated expression of CARD8-AS1 could suppress cellular viability, migration potential, and invasion ability (p < 0.05). The Bcl-2 protein levels were decreased while Bax levels were increased by overexpression of CARD8-AS1 (p < 0.001). miR-650 may thus be a direct target of CARD8-AS1 and Bax may be a direct target of miR-650. Discussion: CARD8-AS1 expression was downregulated in lung adenocarcinoma and associated with several clinical parameters. CARD8-AS1 exerted tumor-suppressive effects by targeting the miR-650 and then regulating Bax expression. CARD8-AS1/miR-650 may serve as novel prognostic biomarkers and potential therapeutic targets for the treatment of lung adenocarcinoma.

Introduction: There is a paucity of reports on non-aeruginosa Pseudomonas (NAPs) in cystic fibrosis, hence this study wished 1). to examine the diversity/frequency of NAPs in an adult CF population, 2) to compare/contrast the microbiology and genomics of NAPs to P. aeruginosa and 3) to propose clinical and laboratory criteria to help determine their clinical significance in CF lung pathology. Materials and Methods: Microbiological data was examined from 100 adult patients with cystic fibrosis from birth to present (31/12/2021), equating to 2455 patient years. 16S rDNA phylogenetic relatedness of NAPs was determined, as well as bioinformatical comparison of whole genomes of P. aeruginosa against P. fluorescens. Results: Ten species were isolated from this patient cohort during this time period, with three species, i.e., P. fluorescens, P. putida and P. stutzeri, accounting for the majority (87.5%) of non-aeruginosa reports. This is the first report of the isolation of P. fragi, P. nitroreducens, P. oryzihabitans and P. veronii in patients with cystic fibrosis. The mean time to first detection of any non-aeruginosa species was 183 months (15.25 years) [median = 229 months (19.1 years)], with a range from 11 months to 338 months (28.2 years). Several of the NAPs were closely related to P. aeruginosa. Discussion: NAPs were isolated infrequently and were transient colonisers of the CF airways, in those patients with CF in which they were isolated. A set of ten clinical and laboratory criteria are proposed to provide key indicators, as to the clinical importance of the non-aeruginosa species isolated.

Pyruvate dehydrogenase (PDH) deficiency is caused by a number of pathogenic variants and the most common are found in the PDHA1 gene. The PDHA1 gene encodes one of the subunits of the PDH enzyme found in a carbohydrate metabolism pathway involved in energy production. Pathogenic variants of PDHA1 gene usually impact the α-subunit of PDH causing energy reduction. It potentially leads to increased mortality in sufferers. Potential treatments for this disease include dichloroacetate and phenylbutyrate, previously used for other diseases such as cancer and maple syrup urine disease. However, not much is known about their efficacy in treating PDH deficiency. Effective treatment for PDH deficiency is crucial as carbohydrate is needed in a healthy diet and rice is the staple food for a large portion of the Asian population. This review analysed the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency caused by PDHA1 pathogenic variants. Based on the findings of this review, dichloroacetate will have an effect on most PDHA1 pathogenic variant and can act as a temporary treatment to reduce the lactic acidosis, a common symptom of PDH deficiency. Phenylbutyrate can only be used on patients with certain pathogenic variants (p.P221L, p.R234G, p.G249R, p.R349C, p.R349H) on the PDH protein. It is hoped that the review would provide an insight into these treatments and improve the quality of lives for patients with PDH deficiency.

Introduction: Defects in the apoptotic process are among the most important events involved in carcinogenesis, and defects in DNASE1, as one of the apoptotic machinery components, plays a role in various types of cancer. Previous studies have indicated significant differences in the DNASE1 polymorphisms in different populations. We hypothesized an association of two polymorphic sites in the exon 8 and the intron 4 of the DNASE1 gene with the risk of gastric cancer. Materials and Methods: The study was carried out on 120 gastric cancer patients and 120 age and sex adjusted controls using PCR and RFLP-PCR. Results: The genotype GG (rs1053874) in exon 8 of DNASE1 (odds ratio [95% confidence interval]) 4.65 [2.10-10.29], p < 0.001) and genotype 2/3 of variable number tandem repeat (VNTR) in the intron 4 (3.75 [1.56-9.01], p = 0.003) are both linked to gastric cancer. Conclusion: We propose that both polymorphic sites have a part to play in gastric cancer, and so may be useful diagnosis markers.

Background: Diabetic Retinopathy (DR) is one of the most severe micro-vascular complications of diabetes mellitus (DM), involving interactions between environmental and genetic risk factors. KCNJ11 gene has a key role in insulin secretion and is of substantial interest in various populations. Methods: A population-based association of 524 T2DM patients was performed to delineate the genetic influence of KCNJ11 polymorphisms (rs5219, c.67A>G or E23K) on the risk of DR in an Iranian population. Genotyping was performed using TaqMan assay. Univariate and MLR analysis controlling for confounders was conducted to evaluate the association between rs5219 and DR. Results: No significant difference was observed in either genotypes distribution (p = 0.83) or allele frequency (p = 0.66) between T2DM individuals with and without DR in any models of inheritance. Genotype-phenotype association showed that DR group carrying GA genotypes, a significantly higher mean age was observed compared with two other genotypes (p = 0.04). MLR analysis indicated that HbAlc with adjusted OR of 1.84 (95% CI, 1.46-2.33, p = 0.00) and first-degree relatives of family history with adjusted OR of 2.85 (95% CI, 1.45-5.58, p = 0.002) were significantly associated with DR, but the c.67A>G genotype is not an independent predictor of retinopathy. Conclusion: Collectively, rs5219 was not associated with DR among Iranians with T2DM.

Objectives: This study aims to investigate hemostatic changes in patients with coronavirus disease (COVID-19) and their relationship to disease severity and survival. Methods: This study included 284 patients with COVID-19 who attended the Security Forces Hospital, Makkah, Saudi Arabia between October 2020 and March 2021, and retrospectively reviewed their demographic, radiological, and laboratory findings. The coagulation profile was assayed at the time of diagnosis for platelet counts using an automated hematology analyzer; Sysmex XN2000 while international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII, ristocetin cofactor (RiCoF), and von Willebrand factor antigen (VWF-Ag) were measured by Stago kits on a Stago automated coagulation analyzer (STA Compact Max^®). Results: In this study, 32.3% of the cases had severe disease, while 8.8% of the cases died. D-dimer, factor VIII, and RiCoF were the only independent predictors of disease severity, with factor VIII and RiCoF having significantly higher areas under the curve (AUCs) than D-dimer (all p < 0.001). Furthermore, age, aPTT, and factor VIII were associated with an increased risk of mortality in multivariate Cox regression analysis, with factor VIII having a higher AUC of 0.98 than aPTT with an optimal cut-off value of >314 IU/dl in predicting mortality. Cases with factor VIII levels >314 IU/dl, compared to those with factor VIII levels <314 IU/dl, were associated with a significantly shorter mean overall survival time (20.08 vs. 31.35 days, p < 0.001), a lower survival rate (30.3% vs. 99.2%, p < 0.001), and a 16.62-fold increased mortality risk. Conclusion: RiCoF is a novel predictor of disease severity in COVID-19, while factor VIII is confirmed as a predictor of severity and mortality in COVID-19 patients and is associated with lower overall survival and increased mortality risk.

Purpose: The purpose of this study was to analyze the effects of miR-640-SLIT1 axis and the Wnt/β-catenin signaling pathway on radiosensitivity of glioma cells. Methods: Relative expressions of miR-640 and slit guidance ligand 1 (SLIT1) in glioma tissues and glioma cell lines U251 and A172 were detected using RT-qPCR. The cell lines were transfected with si-SLIT1 or miR-640 inhibitor to study the radiosensitivity of glioma cells. We detected cell activity using CCK-8 assay, cell migration using wound healing assay, cell invasion using transwell assay, and apoptosis using caspase-3 assay. Results: SLIT1 was upregulated in glioma tissues and cell lines, and inversely correlated with radiation sensitivity. Its knockdown reduced radioresistance, migration, and invasion, but increased apoptosis in U251 and A17 cells. Loss of miR-640 activity upregulated SLIT1, Wnt, and β-catenin protein expression, whereas it inhibited p-GSK-3β protein levels in U251 and A17 cells. These results suggest that miR-640 mediates the radiosensitivity of glioma cells through SLIT1 and the Wnt/β-catenin signaling pathway. Conclusion: The miR-640-SLIT1 axis that regulates the Wnt/β-catenin signaling pathway is a possible therapeutic option for the effective treatment of glioma in combination with radiotherapy.