Annals of clinical and laboratory science最新文献

Objective: Hepatocellular carcinoma (HCC) poses a significant challenge owing to its aggressive nature and elevated mortality rates. Understanding the role of novel therapeutic targets is essential. Although linked to several diseases, the role of the family with sequence similarity 114 member A1 (FAM114A1) in HCC remains unclear.

Methods: Utilizing UALCAN and GEPIA databases, the expression of FAM114A1 in HCC tissues was examined, alongside exploring its correlation with AKT1. FAM114A1 expression in HCC cells was assessed through qRT-PCR experiments. Following lentiviral transduction to suppress FAM114A1 expression in these cells, subsequent analyses involved MTT assays, scratch assays, Transwell analysis, and flow cytometry to investigate the impact of FAM114A1 depletion on cell proliferation, migration, apoptosis, and cell cycle dynamics. Furthermore, Western blot analysis assessed EMT-related proteins (Snail, MMP2, MMP9) and AKT1 expression. Overexpression of AKT1 in HCC cells was performed, and its effects on cell proliferation and migration were assessed using MTT assays and Transwell analysis.

Results: Elevated FAM114A1 expression was observed in HCC tissues and cells. FAM114A1 suppression reduced cell proliferation and migration by modulating AKT1. FAM114A1 knockdown promoted apoptosis, arrested the cell cycle, and inhibited EMT.

Conclusions: Overall, our study suggests that FAM114A1 plays a role in HCC cell proliferation and migration, involving the modulation of AKT1 expression. Furthermore, FAM114A1 impacts apoptosis, cell cycle, and EMT, contributing to HCC development. These findings highlight FAM114A1 as a potential novel therapeutic target for HCC treatment.

Objective: Gestational diabetes mellitus (GDM) is known to be a predisposing factor in the development of type 2 diabetes mellitus in affected mothers and their offspring. Current guidelines recommend a two-hour postpartum glucose tolerance test (OGTT) in patients with a history of GDM. However, compliance rates for ordering and completion has been reported as suboptimal. The COVID-19 pandemic has had significant impact on healthcare systems, requiring the adaptation of novel strategies to manage patients. So far, there is a paucity of data on how this impacts compliance rates for the oral glucose tolerance test. We aimed to compare the compliance rate and impact of the pandemic on OGTT ordering and completion between a women's hospital and a community health center.

Methods: A dual center retrospective cohort study was carried out to compare the compliance for ordering and completion of the two-hour postpartum OGTT in women diagnosed with GDM between a women's hospital and community health center two years pre-COVID-19 (2018-2019) and during the COVID-19 pandemic (2020-2021).

Results: 2569 pregnancies were included during these time periods. Prior to the pandemic, the test ordering compliance at the women hospital was 30.2% vs 79.3% for the community health center. During the pandemic, the test ordering compliance at the women's hospital dropped to 24.8%, while it remained steady at the community center (80.8%). Correspondingly, there was a drop in test completion compliance rate at both centers during the pandemic when compared to rate before the pandemic.

Conclusion: Diagnosis of GDM increased during the pandemic, which may be attributed to factors like sedentary lifestyles, and restructuring of care models, among others. There was increased test ordering and test completion compliance at the community health center compared to the women's hospital, which can be attributed to routine follow-ups and other factors.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). Although the role of LDL-C in FH has been studied, the contribution of high-density lipoproteins (HDL) to CVD in FH remains unknown. This study aimed at highlighting the role of HDL in FH.

Methods: HDL-specific phospholipid efflux (HDL-SPE) assay was developed to predict CVD risk. HDL-SPE was examined in FH patients (n=30) and compared with age- and sex-matched non-FH controls (n=60).

Results: FH patients had significantly lower HDL-SPE levels (0.90±0.12) than controls (1.12±0.10; p<0.05), despite similar HDL-cholesterol levels in both groups (FH: 57.9±18.7 mg/dl; controls: 57.1±13.8 mg/dl). These differences remained significant after adjusting for confounders.

Conclusions: These findings suggest there may be dysfunctionality of HDL in FH.

Objective: This retrospective analysis compares the diagnostic value of placental large vessel (global, partial) and distal villous (complete, segmental) fetal vascular malperfusion (FVM), remote/established, recent and on-going.

Methods: 24 independent abnormal clinical and 46 placental phenotypes were retrospectively statistically analyzed among 1002 consecutive cases, mostly with congenital anomalies in which CD34 immunostaining was performed. Group A: 398 cases without distal FVM and none or up to two large vessels FVM lesions. Group B: 221 cases with distal villous FVM without clustered endothelial fragmentation by CD34 immunostain. Group C: 145 cases with clustered endothelial fragmentation by CD34 immunostain but no clustered sclerotic or mineralized distal villi. Group D: 163 cases with coexistence of distal villous lesions of Group B and Group C. Group E: 75 cases with three or four lesions of large vessel FVM, but no distal villous FVM lesions.

Results: Established and/or remote FVM had clinical/placental associations similar to those of recent FVM, but on-going FVM was most commonly high grade and associated with preterm pregnancies, stillbirth, and fetal growth restriction. Large vessel FVM usually occurs in advanced third trimester pregnancies with fetal congenital anomalies, villitis of unknown etiology, and intervillous thrombi but no direct association with abnormal fetal condition.

Conclusion: FVM was the most common pattern of placental injury in this material. Proximal FVM was more common than distal FVM, suggesting the sequence of occurrence and the likely umbilical cord compression etiology. CD34 immunostaining doubles the sensitivity of placental examination and frequently upgrades the FVM, making it an important adjunct to placental histology.

Objective: CD60 is a T cell marker expressed on blood lymphocytes. CD8+CD60+ T cells may play a role in inflammatory responses due to human immunodeficiency virus-1 (HIV-1). Our laboratory demonstrated that CD8+CD60+ T cells are higher in HIV positive compared with HIV negative subjects. The present study evaluated numbers of CD8+CD60+ in blood of HIV positive children at various stages of HIV-1 disease. The function of CD8+CD60+ T cells in HIV pathogenesis is unknown.

Methods: CD8+CD60+ T cells were measured in blood of HIV positive (N=20) and HIV negative (N=10) children (flow cytometry). Children with HIV were classified into four clinical categories (N, A, B, C) based on symptoms/diagnoses related to HIV infection. Numbers of CD8+CD60+ T cells were compared in HIV positive versus HIV negative children (Wilcoxon signed rank test) and based on clinical categories.

Results: CD8+CD60+ T cells were higher in HIV positive compared with HIV negative children (P=<0.0001). CD8+CD60+ T cells in blood of HIV positive children were highest in the C category; these cells were associated with disease progression (P=0.0158).

Conclusion: CD8+CD60+ T cells were higher in HIV positive children and may be a marker for disease progression.

Objective: Cardiac dysfunction can result from excessive fibrosis in cardiac fibroblasts (CFs) following an acute myocardial infarction (AMI). SIRT3 has been shown to be associated with numerous cardiovascular diseases. This study aimed to investigate the mechanism by which SIRT3 influences myocardial fibrosis following AMI.

Methods: An AMI model was established in rats and echocardiography was used to assess cardiac systolic function. Triphenyl tetrazolium chloride (TTC) and H&E staining were employed to observe the myocardial histopathological status. Masson trichrome staining was used to detect fibrosis, and the changes in expression of fibrosis-related proteins were detected by Western Blot (WB). In this study, we utilized in vitro cell models stimulated by Ang II to investigate the underlying mechanisms. We employed Transwell and CCK-8 assays to detect the function of CFs. Additionally, we used transmission electron microscopy (TEM) to observe the structural morphology of mitochondria, whereas WB was performed to quantify fibrosis-associated proteins and to assay the changes in SIRT3, SRV2, and Drp1.

Results: We observed a significant decrease in the expression of SIRT3 and an increase in mitochondrial fragmentation in rats with AMI. Additionally, we observed upregulation of fibrosis-associated signature proteins and collagen proteins expression. Through the use of vitro Ang II stimulation we observed a downregulation of SIRT3 expression, an increase in mitochondrial fragmentation, and an increase in the proliferation and migration of CFs. Opposite effects were observed when SIRT3 was overexpressed. Additive mitochondrial division agonists were found to stimulate the proliferation and migration of CFs, however, SIRT3 expression was unchanged. Interference with SRV2 and SIRT3 revealed that SIRT3 effectively prevented the expression of SRV2/Drp1, resulting in the inhibition of mitochondrial division and the suppression of CFs proliferative migration.

Conclusion: In summary, SIRT3 can suppress myocardial fibrosis after acute myocardial infarction by regulating SRV2/Drp1-mediated mitochondrial division.

Objective: We validated an automated microfluidic interleukin-6 (IL-6) immunoassay on the Ella platform for clinical use.

Methods: The assay was validated for precision, lower limit of quantification, analytical measurement range, accuracy, specificity, interference of biotin, tocilizumab, GP130, IL-6Rα, hemolysis, icterus, and lipemia, and establishing the reference value. The clinical performance was evaluated in 96 COVID-19 patients.

Results: The within-run and between-run coefficient of variations (CV) ranged 1.8%-4.8%. This assay has an analytical measurement range (AMR) 0.7-2652 pg/ml. There was a moderate correlation between Ella IL-6 assay (y) and a Luminex Quantitative Multiplex Bead Assay in a reference lab (x): y=8.561x-475.38, R=0.5047, SEE=1592.8 pg/mL, N=48). Measurement of IL-6 in plasma samples from 45 healthy adults showed the upper limit of reference of 5.0 pg/mL. 95.83% (95% CI: 89.67%-98.85%) of COVID-19 patients had IL-6 >5.0 pg/mL. This assay is resistant to the interference from hemoglobin up to 1,144 mg/dL, triglyceride 1,699 mg/dL, bilirubin 35 mg/dL, biotin 1000 ng/mL, tocilizumab 240 μg/mL, IL-11 50,000 pg/mL, GP130 50,000 pg/mL, and IL-6Rα 1,000 pg/mL.

Conclusions: The IL-6 assay on the Ella platform is robust with minimum manual operation. The analytical and clinical performance characteristics meet the clinical needs.

Objective: Both chronic kidney disease and its main treatment, hemodialysis (HD), are associated with hematological abnormalities. However, little is known about how starting hemodialysis when already in end-stage renal disease (ESRD) affects hematological parameters. This study investigated the effect of HD on hematological and coagulation markers among ESRD patients.

Methods: A retrospective study was carried out on 43 HD-ESRD patients from January to December 2022. The data were collected from Sabt Alalaya General Hospital in Belgarn, Saudi Arabia. Using GraphPad Prism, multiple unpaired t-tests were utilized to compare hematological and coagulation markers between the patients and healthy subjects.

Results: The 43 HD-ESRD patients (46.5% male and 53.5% female) ranged in age from 20 to 89 years. The data obtained from our analysis unsurprisingly revealed significant variation in hematological parameters and coagulation patterns among HD-ESRD patients. Most notably, there were gradual and significant changes in platelet, MCV, MPV, and INR values during the assessment time.

Conclusion: This investigation verified the possible occurrence of macrocytosis and thrombotic conditions among patients with ESRD who undergo HD. It is recommended to closely observe patients undergoing this procedure, with a specific focus on platelet, MCV, MPV, and INR levels as potential indications.