Objectives Cancer is a leading global health issue with complex causes. Conventional treatments often face challenges like drug resistance and toxicity. Plant-derived compounds such as artemisinin have gained interest due to their diverse anticancer mechanisms, including ROS generation and apoptosis induction. In this study, the biological activities of ART-FB, a hybrid compound combining benzothiophene and artemisinin, were systematically investigated for the first time. Methods ART-FB's cytotoxicity was tested on various human cancer cell lines (Caco-2, LNCaP, HeLa, A549) and HUVEC via MTT assay. Colony formation, scratch-wound, and Annexin V/PI assays were used to assess proliferation, migration, and apoptosis. Apoptotic gene expression was analyzed by qPCR. Anti-inflammatory effects were studied in LPS-stimulated RAW264.7 cells via Griess assay and qPCR. Results ART-FB showed selective cytotoxicity in Caco-2, LNCaP, HeLa, and A549 cancer cell lines, with lower toxicity in non-cancerous HUVEC cells. It effectively suppressed proliferation, colony formation, and migration, especially in LNCaP and A549 cells, suggesting potential anti-metastatic activity. Annexin V/PI staining and gene expression analysis confirmed that ART-FB induces apoptosis via both intrinsic and extrinsic pathways, with the strongest effects in LNCaP and Caco-2 cells. In LPS-stimulated RAW264.7 macrophages, ART-FB significantly reduced nitric oxide levels and downregulated iNOS, COX-2, TNF-alpha, and IL-6, while upregulating IL-10, suggesting dual anticancer and anti-inflammatory action. Conclusions ART-FB exhibits both anticancer and anti-inflammatory properties, targeting key pathways involved in tumor growth and immune response. These findings indicate that ART-FB is a promising candidate for further preclinical development as a multifunctional therapeutic agent.
Objectives: Inflammatory responses are pivotal in the progression of acute lung injury (ALI), with circular RNA FLNA (circFLNA) emerging as a key suppressor in sepsis-induced ARDS models. This study investigates how circFLNA, in conjunction with extravascular lung water index (EVLWI) and lung ultrasound score (LUS), predicts outcomes in ALI patients. Methods: CircFLNA expression was quantified via qRT-PCR, and its prognostic significance, alongside EVLWI and LUS, was evaluated using Logistic regression analysis and receiver operating characteristic (ROC) curve. Results: Serum circFLNA levels were markedly higher in ALI patients compared to controls (p<0.001). Logistic regression analysis indicated that EVLWI (OR=1.565, 95 % CI=1.266-1.935, p<0.001), LUS (OR=1.543, 95 % CI=1.214-1.962, p<0.001), and circFLNA (OR=6.209, 95 % CI=1.880-20.515, p=0.003) were distinctly related to death of ALI patients. The area under the curve (AUC) of circFLNA for the death of ALI patients was 0.717 (95 % CI=0.625-0.810) with a sensitivity of 0.722 and a specificity of 0.676. ROC demonstrated that a combination of circFLNA, EVLWI, and LUS had high prognostic value for 28-day death of ALI patients (AUC=0.909, 95 % CI=0.863-0.955, sensitivity=0.944, specificity=0.748, p=0.001). Conclusions: CircFLNA was upregulated in ALI patients and was positively correlated with a high risk of death in ALI patients. Combination of EVLWI, LUS, and circFLNA had a high predictive value for death in ALI patients.
Objectives: Serum protein electrophoresis is a widely used technique for the detection of multiple myeloma and other serum protein disorders. Paraprotein quantification can be performed using either the perpendicular drop or the tangent skimming method. The aim of this study was to evaluate both methods and to investigate inter-observer variability in the quantification of paraproteins in serum samples analysed by capillary zone electrophoresis. Methods: Laboratory data from serum protein electrophoresis performed by capillary zone electrophoresis between October 1 and December 31, 2024 were reviewed. Patients aged 18-100 years were included in the study. Paraprotein quantification results were evaluated independently by three clinical biochemists using both perpendicular drop or the tangent skimming quantification methods. Results: Paraprotein levels quantified by the perpendicular drop method were significantly higher than those quantified by the tangent skimming method across all three observers (p<0.001 for all). A very strong correlation was observed between the two methods for each observer (r=0.92, r=0.93, and r=0.93; p<0.001 for all). A discrepancy was observed between observers 1 and 2 in hypergammaglobulinemic samples using both methods. However, observer 3 consistently reported higher paraprotein levels than observers 1 and 2 using both methods (p<0.05 for all). Conclusions: Although serum protein electrophoresis is an established laboratory technique, a lack of standardization persists in result reporting across laboratories. Switching between quantification methods during patient follow-up is not recommended. It is recommended that using the same method, the same laboratory, and ideally the same clinical biochemist for result interpretation.
Objectives: This study aimed to determine the rate of unnecessary test requests in a university hospital biochemistry laboratory by evaluating tests against the Turkish Ministry of Health's "Rational Test Request Procedure" guidelines, specifically focusing on "Test Request Duration (Day)." Methods: This retrospective observational study analyzed five biochemistry tests (Vitamin B12, Vitamin D, LDL cholesterol, LDH, and Folate) with the longest recommended retesting periods. The study covered 30 months (July 6, 2019 - January 7, 2022) to compare test request patterns before and after the national policy's implementation. Data from the hospital information system defined unnecessary requests as those ordered for the same patient before the minimum suggested retesting interval. Associated costs were estimated using official Social Security Institution reimbursement values. SPSS v26 was used for frequency analyses and Chi-square tests to assess associations between unnecessary ordering and physician gender/title, patient age/gender, and clinical setting. Results:Of 490,344 test requests made, 199,553 were inappropriate (40.7 %), which accounted for 49.0 % cumulative spend. LDH had highest inappropriate use (61.7 %), with over 90 % of internal medicine test requests identified as redundant. Decreased considerably were test requests for Vitamin D by 70 % since policy introduction. Conclusions: In spite of national standards, improper test use endures when it comes to non-specific biomarkers. The dramatic overutilization of LDH was identified as the most significant cause of redundant testing and expense. Directed training as well as decision-support tools are thus imperative in order to streamline wasteful testing and downstream improvement.
Objectives: This study aims to explore the diagnostic and prognostic value of lncRNA PTOV1-AS1 in patients with breast cancer (BC). Methods: This study included 104 BC patients as case group and 86 healthy volunteers as control group. Serum PTOV1-AS1 expression was detected in all subjects by RT-qPCR, and receiver operating characteristic (ROC) curves were plotted to assess the clinical diagnostic value of PTOV1-AS1 for BC. Serum PTOV1-AS1 expression under different clinicopathological characteristics in BC patients was detected by RT-qPCR. The prognostic performance of PTOV1-AS1 in BC was assessed using the Kaplan-Meier method and Cox regression analysis. Results: Serum PTOV1-AS1 expression in BC patients was remarkably higher than that in healthy controls. The area under the ROC curve (AUC) was 0.954, the sensitivity was 81.70 %, and the specificity was 97.67 %, which demonstrated that PTOV1-AS1 could distinguish BC patients from healthy volunteers. RT-qPCR results indicated significant differences in the expression of PTOV1-AS1 among differentiation, tumor nodes metastasis (TNM) stage and lymph node metastasis (LNM). Additionally, patients with low PTOV1-AS1 expression had better progression-free survival (PFS) than those with high expression, and PTOV1-AS1 was an independent prognostic biomarker for BC. Conclusions: PTOV1-AS1 expression is upregulated in the serum of BC patients and is closely linked to poor prognosis. It provides a new perspective and theoretical basis for the diagnosis and prognostic assessment of BC, and is a potential biomarker.
Objectives This research sought to explore the clinical application value of serum miR-148a-3p combined with computed tomography (CT) features for differentiating benign from malignant pulmonary nodules and assessing patient prognosis.Methods The experimental group included 80 patients with malignant pulmonary nodules, and the control group consisted of 70 patients with benign pulmonary nodules. Serum expression of miR-148a-3p was quantified using RT-qPCR. The diagnostic performance of serum miR-148a-3p and nodule diameter for distinguishing malignant pulmonary nodules was assessed via the receiver operating characteristic (ROC) curve. Overall survival was estimated using the Kaplan-Meier method, and risk prediction was conducted using the multivariate Cox regression.Results Compared with benign nodules, malignant nodules displayed significantly different CT imaging characteristics, particularly in terms of larger diameters, ground-glass or mixed-density patterns, lobulation, spiculation, vascular convergence, pleural indentation, and calcification features. The expression of miR-148a-3p was significantly lower in the malignant nodule group. The combination of miR-148a-3p expression and CT features yielded enhanced diagnostic accuracy (AUC=0.8966) for distinguishing benign and malignant nodules. However, these results were obtained from a single retrospective cohort without independent validation, which may lead to an overestimated AUC. Further multi-center studies with independent validation were needed to verify its real diagnostic performance in broader clinical populations. Moreover, low miR-148a-3p expression was associated with poorer survival outcomes with malignant pulmonary nodules and may be an independent factor influencing disease progression.Conclusions The integrated use of serum miR-148a-3p and CT exhibited superior clinical diagnostic performance in differentiating benign from malignant pulmonary nodules.
Objectives The aim of our study was to evaluate the diagnostic and prognostic significance of systemic immune inflammation index (SII) and other hematological parameters in Alzheimer's disease (AD), the most common cause of dementia in the world. Methods This retrospective study analyzed 340 patients with Alzheimer's disease and 340 healthy controls. Demographic, cognitive, SII, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-neutrophil ratio (MNR), platelet-to-monocyte ratio (PMR), and biochemical parameters were compared between the groups. Results Neutrophil, monocyte, and platelet counts, as well as NLR and SII values, were significantly higher in the AD group compared to the control group. However, lymphocyte, hemoglobin, high-density lipoprotein cholesterol, and PMR values were lower in the patient group (all p<0.001). Mini Mental State Examination scores were found to be negatively correlated with NLR, SII, and monocyte counts, and positively correlated with lymphocyte counts and PMR. In the multivariate model, PMR and MNR were found to be independent predictors of AD, while SII and NLR were not. A positive correlation was found between disease severity and SII, and a negative correlation was found between MNR. Conclusions SII and NLR are elevated in Alzheimer's disease (AD) and correlate with cognitive function loss. MNR and PMR are attracting attention as independent predictors of AD, providing new data compared to previous studies. These readily and inexpensively obtained parameters may serve as potentially practical tools for early or preclinical diagnosis, risk stratification, and monitoring of Alzheimer's disease.
Objectives: Alzheimer's disease (AD) is a chronic brain disorder. The progression of AD is known to cause irreversible neurodegeneration, and loss of neuronal density causes memory dysfunction. The administration of amyloid-beta(1-42) (A beta) oligomer causes AD in experimental animals. However, the role of santonin (ST) in the regulation of ubiquitin-conjugating enzyme E2B (UbcE2B) in AD conditions has not been reported yet. Hence, the present study was designed to investigate the role of ST against A beta oligomer-induced AD in mice. Methods: The AD in mice was induced by intracerebroventricular (i.c.v.) injection of A beta oligomer (4 mu g/4 mu L) in mice. The test compounds, i.e., ST (30, 60, and 120 mg/kg of body weight) and donepezil (DP, 2 mg/kg), were administered orally (p.o.) for 21 consecutive days. The behavioral changes, i.e., the Morris water maze (MWM) test, Y-maze alternation test, and novel object recognition test (NORT), were assessed as per the experimental protocol. Furthermore, biomarkers, i.e., brain acetylcholinesterase (AChE) activity, thiobarbituric acid reactive substances (TBARS), catalase, and UbcE2B levels were estimated in mouse brain tissue samples. Besides, A beta-associated brain histopathological changes were also evaluated by the eosin and hematoxylin staining method. Results: The results revealed that ST attenuates the A beta-induced changes in cognitive behaviors, biomarkers, and histopathological levels. Conclusions: Hence, ST is considered a potential therapeutic agent for A beta-associated AD progression. It may be due to its potential anti-oxidative, anti-inflammatory, and activation of UbcE2B activity. However, more extensive studies are required to prove this therapeutic potency in different AD conditions in various animal species.
Objectives Non-alcoholic fatty liver disease (NAFLD) is a progressive disease. The diagnostic performance of current non-invasive biomarkers for NAFLD remains suboptimal. Circular RNAs (circRNAs) have emerged as potential biomarkers and therapeutic targets due to their involvement in disease progression. This study investigated the diagnostic potential and underlying mechanisms of hsa_circ_0004662 in NAFLD.Methods The study combined bioinformatics and experimental approaches. Analysis of the GSE134146 dataset revealed differentially expressed circRNAs, leading to RT-qPCR verification of hsa_circ_0004662 in clinical cohorts. Cellular models were utilized to assess triglyceride (TG) content in HepG2 cells and fibrosis markers in LX-2 cells; potential miRNA interactions were examined through integrated prediction and validation.Results Screening of the GSE134146 dataset revealed that hsa_circ_0004662 was the most markedly upregulated circRNA. This finding was confirmed in our independent clinical cohort, comprising 156 NAFLD patients and 105 healthy controls. Compared with healthy controls, the expression of hsa_circ_0004662 was gradually upregulated in plasma samples of patients with non-alcoholic steatohepatitis (NASH) and NASH-associated liver fibrosis (NASH-AF). hsa_circ_0004662 promoted lipid accumulation in HepG2 cells and fibrosis in LX-2 cells. Mechanistically, hsa_circ_0004662 likely interacts with miR-532-3p to promote NAFLD.Conclusions Hsa_circ_0004662 holds potential as a non-invasive diagnostic biomarker and therapeutic target for NAFLD. Further validation and mechanistic studies are warranted to elucidate its role in disease progression.
Objectives: This work aimed to examine the aberrant expression of miR-125a-5p in chronic heart failure (CHF) patients and assess its clinical significance. Methods: Participants included healthy controls and CHF patients. miR-125a-5p levels were analyzed by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Multivariate Cox regression analysis identified the risk of CHF development. Receiver Operating Curve (ROC) analysis was conducted to evaluate the diagnostic accuracy of serum miR-125a-5p for CHF. Kaplan-Meier analysis was generated to assess the survival outcomes. A myocardial injury cell model was created by treating cardiomyocytes with doxorubicin (DOX). Cell proliferation was assessed using Cell Counting Kit-8, while apoptosis rates were quantified by flow cytometry. The concentration of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) was measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: Serum miR-125a-5p levels were significantly reduced in CHF patients. ROC curve analysis revealed an area under the curve (AUC) of 0.9446 for miR-125a-5p in distinguishing CHF from controls. Furthermore, low serum miR-125a-5p expression was significantly associated with poor patient prognosis and emerged as an independent risk factor for adverse outcomes in CHF patients. In vitro experiments demonstrated that DOX treatment significantly suppressed miR-125a-5p expression in cardiomyocytes, leading to inhibited cell proliferation and increased apoptosis. Conversely, overexpression of miR-125a-5p effectively reversed these DOX-induced cellular injury effects and suppressed the upregulation of NT-proBNP expression. Conclusions: Serum miR-125a-5p expression is downregulated in patients with CHF and may serve as a novel diagnostic and prognostic biomarker. Its mechanism may involve exerting cardioprotective effects during CHF progression by regulating cardiomyocyte proliferation, apoptosis, and stress responses.
Objectives The study aims to show that in the follow-up of light chain multiple myeloma (LCMM) patients using the electrophoresis tests as used in multiple myeloma (MM) patients with intact (heavy chain-associated) M protein, may cause unnecessary testing.Methods The laboratory information system was searched retrospectively between 1 January 2022 and 31 December 2022. LCMM patients were characterized with positive urine immunofixation electrophoresis (UIFE), negative or positive serum immunofixation electrophoresis (SIFE), and both without any heavy chain component.Results The randomly selected 10 patients were 5 males and 5 females, with a median follow-up time of 42 months (95 % CI 30-82 months). During the follow-up of the 10 patients, a total of 215 serum protein electrophoresis (SPE), 351 SIFE, and 306 UIFE tests were studied. Overall, 4 of the 215 SPE tests, 62 of 351 SIFE, and 142 of 306 UIFE tests were reported as positive. In 62 positive SIFE tests, 33 were evaluated to be due to Daratumumab drug interference. The other 29 positive SIFE tests were accompanied by concomitant positive UIFE tests. When scored according to the official scoring system (SUT), total SPE, SIFE, and UIFE tests performed in the follow-up of these 10 patients cost a total of 66,913 points. Negative SPE and negative or avoidable SIFE tests cost 38,764 of 66,913 points (58 %).Conclusions The high rate of negative SPE and negative or avoidable SIFE tests indicated that the use of these tests should be carefully considered by the clinician in the follow-up of LCMM patients. Clinical guidelines should include clear directions for follow-up of subtypes of MM, particularly for LCMM.
Objectives Circular RNAs are valuable biomarkers for cancer therapy. hsa_circ_0004928 expression is dysregulated in gastric cancer (GC). The study aims to further explore the roles of hsa_circ_0004928 in GC and the possible mechanism. Methods The expression of hsa_circ_0004928 in GC tissues and cells was analyzed via qRT-PCR. The predictive value of hsa_circ_0004928 for GC severity and prognosis was assessed. The interaction between hsa_circ_0004928 and miR-375 was verified by a database and confirmed using RIP. The impacts of hsa_circ_0004928 and miR-375 on GC cell function were evaluated. Results hsa_circ_0004928 was upregulated in GC. High hsa_circ_0004928 expression was related to advanced clinical symptoms of GC. hsa_circ_0004928 showed a significant positive correlation with common tumor markers, including CA199, CEA, and CA724. hsa_circ_0004928 was identified as an independent prognostic factor, with its high expression level associated with poorer survival outcomes. hsa_circ_0004928 demonstrated favorable predictive value in the diagnosis of GC. Furthermore, miR-375 was a potential target gene of hsa_circ_0004928; knockdown of hsa_circ_0004928 significantly inhibited the growth and metastasis of GC cells, while miR-375 reversed these effects. Conclusions hsa_circ_0004928 is closely linked to GC severity and is a promising prognostic and diagnostic indicator. hsa_circ_0004928 promotes GC progression via regulating miR-375.
Objectives The primary aim of this research endeavor was to investigate the effects of small nucleolar RNA host gene 7 (SNHG7) in isoflurane (ISO) protection against oxidative stress-induced myocardial injury.Methods AC16 cells were treated with H2O2, followed by ISO treatment. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was utilized to measure the levels of SNHG7, miR-378a-5p, and Cyclin dependent kinase 1 (CDK1). Cell viability and apoptosis were evaluated by cell counting kit 8 (CCK-8) and flow cytometry; The inflammatory factors wrere quantified through enzyme-linked immunosorbent assay (ELISA); oxidative stress indicators were detected using commercial reagents. Dual luciferase reporter (DLR) experiment was performed to confirm target gene binding.Results SNHG7 was significantly upregulated in H2O2-induced AC16 cells. H2O2-induced myocardial injury resulted in reduced cell viability, increased apoptosis, inflammation, and oxidative stress. However, SNHG7-upregulation reversed the protective effects of ISO. Besides, miR-378a-5p targeted SNHG7 and was negatively regulated by SNHG7. The miR-378a-5p directly counteracted the aggravation of myocardial cell damage caused by SNHG7 overexpression. In addition, CDK1 was a target gene of miR-378a-5p in AC16 cells.Conclusions This study showed that H2O2-triggered oxidative stress caused damage in AC16 cells. ISO treatment reduced this myocardial damage. The mechanism may involve SNHG7 acting as a miRNA sponge that co-regulates CDK1 expression with miR-378a-5p, aggravating H2O2-induced myocardial injury.
Objectives This study aimed to investigate the pharmacological effects and mechanisms of Xihuangcao (XHC) in a rat model of Intrahepatic cholestasis (IC). Methods Network pharmacology analysis was conducted to identify the main active ingredients and key targets of XHC in alleviating IC, validated through molecular docking. An IC rat model was then established to evaluate the efficacy of XHC. The potential mechanisms were verified using hematoxylin-eosin (HE) staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting (WB). Results Network analysis identified CAR as the key target for XHC's effects on IC, with active ingredients including luteolin, quercetin, isorhamnetin, kaempferol, a quercetin derivative, and skrofulein. Molecular docking confirmed the strong binding affinity of these components to CAR. Compared to the model group, high-dose XHC significantly increased the body weight of rats (p<0.01), and decreased serum biochemical markers related to IC, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin levels (p<0.01). HE staining showed reduced hepatocyte necrosis and inflammation. Additionally, RT-qPCR and WB confirmed increased mRNA and protein levels of MRP2 and CAR in the high-dose XHC group (p<0.001). Conclusions XHC may alleviate IC through the CAR/MRP2 signaling pathway, providing pharmacological support for its use in treating IC.
Objectives As China's population ages, a dramatic rise in osteoporotic fracture incidence is expected to happen. The current study was designed to determine the expression level and the cellular function of hsa_circ_0008668 during osteoblast and osteoclast differentiation.Methods The GSE159121 and GSE161361 datasets were downloaded and analyzed. Serum samples from patients with osteoporotic fractures were collected to determine the hsa_circ_0008668 levels. The effects of hsa_circ_0008668 on the levels of respective differentiation markers of osteoblasts and osteoclasts were examined by in vitro experiments. Downstream targets of hsa_circ_0008668 were predicted and validated by rescue experiments.Results GSE159121 and GSE161361 datasets identified hsa_circ_0008668 as a downregulated circRNA in cases of osteoporotic fracture. Overexpression of hsa_circ_0008668 in osteoclasts was found to inhibit cell osteoclastic marker levels, while the knockdown of hsa_circ_0008668 in osteoblasts was found to inhibit the expression of osteogenic markers. miR-140-3p was a target of hsa_circ_0008668 and rescued the functions of hsa_circ_0008668 on osteoblast and osteoclast differentiation.Conclusions Hsa_circ_0008668 may be a regulator of osteoblast and osteoclast differentiation by targeting miR-140-3p.
Objectives Although lithium (Li) remains a first-line treatment for bipolar disorder (BD), its exact mechanisms of action are still heavily debated. Because neurosteroid (NS) dysregulation plays a critical role in psychiatric disorders, this study looked into whether some of lithium's effects are mediated through altering intracellular NS levels. Methods We assessed the effects of Li (0.5-25 mM) on SH-SY5Y cell viability over 24-72 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Following this, we measured intracellular NS levels at specific doses and durations via LC-MS/MS. Results While 0.5-2.5 mM Li treatments preserved cell viability, doses >= 5 mM markedly reduced it (p<0.05). At a 1 mM non-toxic dose (24 h), we noted a significant buildup in pregnenolone, progesterone, 17-OH progesterone, and dehydroepiandrosterone (DHEA) (p<0.05). Conversely, treating cells with 25 mM Li spiked pregnenolone but significantly depleted androstenedione (p<0.05), and it drove up dehydroepiandrosterone sulfate (DHEAS) across all time points. Conclusions In conclusion, Li distinctly alters neurosteroidogenesis in a dose and time-dependent manner. Although preliminary, these in vitro findings offer remarkable insights, suggesting that NS pathways might mediate lithium's clinical efficacy, warranting further comprehensive studies.
Objectives: Coronary artery ectasia (CAE) is characterised by an increase in the diameter of a coronary artery of >= 1.5 times its diameter at the adjacent vessel. It is evident that alterations in the extracellular matrix changes contribute to the development of CAE. Lysyl oxidases (LOXs) are copper-dependent monoamine oxidase enzymes that play a crucial role in the regulation of connective tissue. Deficiencies in these enzymes have been linked to vascular changes, consequently leading to cardiovascular diseases. The objective of this study was to assess the association between the LOX-G473A (rs1800449) variation and inflammatory markers in CAE development. Methods: The current cross-sectional study includes 88 patients whom CAE was confirmed in one of the coronary arteries by coronary angiography and 75 controls with positive exercise tests and angiographically normal coronary arteries without any typical ischemic symptoms and family history of cardiac diseases. Luminex technology was used to detect inflammatory markers. The fluorescence end-point PCR method was used for genotyping. Results: Significantly higher plasma levels of TNF-alpha, sE-selectin, and hypercholesterolemia were observed in the CAE group (p<0.05). Male gender was found as risk factor for CAE. Although the genotype and allele distributions did not showed statistical significance, CAE patients with GA genotype had significantly higher levels of TNF-alpha and sP-selectin compared to patients with GG genotype. In addition, patients with right coronary artery (RCA) ectasia had higher TNF-alpha levels than patients with non-RCA ectasia. Conclusions: Our findings could suggest that LOX-G473A polymorphism could be associated with the increase in inflammatory markers and CAE development.
Objectives Hypertrophic scar (HS), a type of pathological scar, arises from excessive fibrosis in the process of skin wound repair. Circular RNAs (circRNAs) are involved in regulating fibroblast functions in HS, but the role of circ_0008667 remains unclear. To investigate the expression and regulatory mechanism of circ_0008667 in hypertrophic scar fibroblasts (HSFs).Methods This study employed HSFs and normal skin fibroblasts (NSFs). The expression levels of circ_0008667, miR-324-5p, HOXA9, and collagen-related genes were detected using RT-qPCR. After cell transfection, the impacts of the relevant factors on HSFs proliferation and apoptosis were examined using CCK-8 and apoptosis assay. The target binding relationship is determined using the dual-luciferase reporter assay.Results Circ_0008667 was highly expressed in HSFs. Its silencing inhibited HSF proliferation, promoted apoptosis, and reduced collagen-related genes, including Collagen Type I (Col I), Collagen Type III (Col III), and alpha-smooth muscle actin (alpha-SMA) expression. Circ_0008667 can directly interact with miR-324-5p and negatively regulate its expression. MiR-324-5p reverses the promoting effects of circ_0008667 on HSFs. HOXA9 is a target of miR-324-5p, and when overexpressed, it can reverse the inhibitory effects of miR-324-5p.Conclusions Circ_0008667 mediates excessive proliferation and fibrosis of HSFs via regulating the miR-324-5p/HOXA9 axis, suggesting its potential as a target for HS treatment.
Objectives Proteinuria is a key biomarker for early detection, staging, and monitoring of chronic kidney disease (CKD). This study aimed to evaluate the diagnostic accuracy of the Dirui FUS-3000 Plus automated urine analyzer by comparing urine dipstick test results with the spot urine protein-to-creatinine ratio (PCR) as the reference method. Methods A retrospective cross-sectional analysis was conducted on 6,543 spot urine samples. Dipstick results were assessed in two ways by categorizing "trace" as either negative or positive. Diagnostic parameters including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa were calculated for two PCR cut-off values (150 mg/g and 200 mg/g). Results Diagnostic performance of the dipstick test varied according to the PCR cut-off value and the interpretation of trace results. When trace was classified as negative, sensitivity and specificity were 71.3 % and 98.3 % at a PCR cut-off of 200 mg/g, and 60.2 % and 99.1 % at a cut-off of 150 mg/g, with Cohen's kappa values of 0.703 and 0.554, respectively (all p<0.001). When trace was classified as positive, sensitivity and specificity were 85.3 % and 88.8 % at a PCR cut-off of 200 mg/g, and 75.8 % and 92.7 % at a cut-off of 150 mg/g, with corresponding kappa values of 0.741 and 0.662 (all p<0.001). McNemar's test was statistically significant in all analyses. Conclusions The Dirui FUS-3000 Plus provides competitive diagnostic performance in proteinuria screening. Consideration of trace results and urine concentration is crucial to minimize misclassification, especially in borderline proteinuria cases.
Objectives The dysregulation and function of lncRNA DLEU2 (DLEU2) in human cancers have been widely reported. Its functional role in ccRCC remains unclear. The significance of DLEU2 in ccRCC and its potential molecular mechanism were investigated to explore a reliable biomarker.Methods One hundred and six ccRCC patients were included, and the expression of DLEU2 in tissues was evaluated by qPCR. The biological effect of DLEU2 on related cellular processes was assessed. The regulation of miR-186-5p by DLEU2 was studied with the luciferase-reporter assay.Results DLEU2 showed a significantly higher expression in ccRCC in comparison with normal samples. The upregulation of DLEU2 indicates advanced TNM stage and positive lymph node metastasis of patients. DLEU2 was an independent prognostic biomarker of ccRCC. Silencing DLEU2 significantly suppressed the proliferation, migration, and invasion of ccRCC cells. The negative regulation of miR-186-5p by DLEU2 was considered the underlying mechanism of DLEU2.Conclusions Upregulated DLEU2 indicated malignant development and poor prognosis of ccRCC. Moreover, DLEU2 acted as a tumor promoter via modulating miR-186-5p.
