Bosnian Journal of Basic Medical Sciences (BJBMS)
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Hsa_circ_0001492 regulates the hsa-miR-145-5p/ovarian carcinoma immunoreactive antigen domain 2 axis to promote the progression of lung adenocarcinoma
Get PDFCircular RNA (circRNA) has been proven to be a key regulator in a range of tumor illnesses, such as lung adenocarcinoma (LUAD); however, the regulatory mechanisms of circRNA remain unclear. In this study, circRNA (hsa_circ_0001492) in LUAD was examined for its regulatory and functional potential. qRT-PCR was used to assess the hsa_circ_0001492 level in LUAD. The RNAse R digestion test was employed to isolate hsa_circ_0001492. The primary location of hsa_circ_0001492 enrichment in LUAD cells was identified through a nucleoplasmic separation test. LUAD cell migration, proliferation, and spherogenicity were examined using wound healing, transwell, EdU, and cell spherogenicity assays. The association between miR-145-5p and hsa_circ_0001492/ovarian carcinoma immunoreactive antigen domain 2 (OCIAD2) was validated using a dual luciferase experiment. The interaction between sh-hsa_circ_0001492 and miR-145-5p was confirmed through an RNA pull-down assay. The effects of hsa_circ_0001492, miR-145-5p, and OCIAD2 on LUAD tumor development were examined using xenograft mouse models and immunohistochemistry tests. Results showed a higher amount of hsa_circ_0001492 in LUAD. The cytoplasm of LUAD cells was observed in the area where hsa_circ_0001492 mainly accumulated; hsa_circ_0001492 enhanced LUAD cell migration, proliferation, and sphere-forming ability. MiR-145-5p and OCIAD2 were identified as targets of hsa_circ_0001492 and miR-145-5p, respectively. The level of OCIAD2 was increased by hsa_circ_0001492 through targeted binding to miR-145-5p. In nude mice, tumor growth was inhibited by silencing hsa_circ_0001492, while knockdown of miR-145-5p and overexpression of OCIAD2 promoted the growth of LUAD tumors. In conclusion, hsa_circ_0001492 regulates the hsa-miR-145-5p/OCIAD2 axis to promote the progression of LUAD, and could be a useful target for the diagnosis and treatment of LUAD
Research progress on melatonin, 5-HT, and orexin in sleep disorders of children with autism spectrum disorder
Get PDFSleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-hydroxytryptamine (5-HT), and orexin are key neurotransmitters that regulate the sleep–wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with ASD, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep–wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD
The association of rs25487 of the XRCC1 gene and rs13181 of the ERCC2 gene polymorphisms with the ovarian cancer risk
Get PDFOvarian cancer (OC) is the most lethal gynecological cancer worldwide. DNA damage plays an important role in cancer development, and the proteins encoded by XRCC1 and ERCC2 are important components of the DNA repair system. This study aimed to examine the relationship between the rs25487 XRCC1 and rs13181 ERCC2 polymorphisms and the risk of OC development in women from the Moscow region. DNA was isolated from the blood of 129 healthy donors and tissues and blood samples from 125 patients with OC and studied using real-time PCR. An increase in odds ratios (OR) was obtained for OC tissue and blood for both T (OR = 1.46, 95% confidence interval [CI] = 1.22–1.76, P = 0.00005), and for T/T of rs25487 XRCC1. The most significant OR values were found for the T/T genotype using the codominant model (OR = 2.11, 95% CI = 1.44–3.07, P = 0.00006) and dominant model (OR = 3.13, 95% CI = 1.44–6.79, P = 0.0025) for the pooled blood and tissue groups. For rs13181 ERCC2, differences were observed for the T/G genotype in OC tissues (OR = 0.69, 95% CI = 0.51–0.92, P = 0.011) in the codominant model. In this study, the association of allele T and genotypes of rs25487 XRCC1 and T/G of rs13181 ERCC2 with OC was shown. Our results indicate that these polymorphisms may be involved in the pathogenesis of OC and are promising for further studies on therapeutic applications in OC
Combined sonographic optic nerve sheath diameter and cerebral oximeter for predicting neurological outcome after cardiac arrest
Get PDFCardiac arrest (CA) remains a critical global health issue with high rates of mortality and morbidity. Accurate prediction of neurological outcomes in post-CA patients is essential for optimizing management strategies. Optic nerve sheath diameter (ONSD) and near-infrared spectroscopy (NIRS) are emerging as promising tools for evaluating brain oxygenation and intracranial pressure. However, the potential benefits of combining these methods for improved prognostic accuracy have not been thoroughly explored. This study investigates whether the combined use of ultrasonographic ONSD and NIRS measurements enhances the prediction of neurological outcomes after CA. In this prospective study, ONSD measurements were obtained three times at 24-hour intervals, while regional hemoglobin oxygen saturation (rSO2) using NIRS was recorded twice. Neurological outcomes were assessed using the Full Outline of Unresponsiveness (FOUR) and Cerebral Performance Categories (CPC) scores for both early and late evaluations. Results indicated that 47.5% of patients had poor outcomes and 52.5% had good outcomes based on the FOUR score, while 65% had poor outcomes and 35% had good outcomes according to the CPC score. The combination of ONSD and NIRS measurements showed superior prognostic performance compared to either method alone. While standalone NIRS measurements taken after 24 hours exhibited limited predictive value, combining ONSD and NIRS provided a more reliable approach for neurological assessment in the short term following CA. This integrated method may improve prognostic accuracy and support better clinical decision-making
Research progress and application status of organoid in breast cancer subtypes
Get PDFBreast cancer (BC) is a prevalent malignant tumor that poses a significant health risk to women. The complexity of basic BC research and clinical treatment is influenced by multiple factors, including age, fertility, hormone metabolism, molecular subtypes, and tumor grading and staging. Traditional in vitro models often fall short of meeting modern research demands, whereas organoids—an emerging 3D primary culture technology—offer a unique platform that better replicates the tumor microenvironment (TME). Coupled with advances in high-throughput sequencing technologies, organoids have become increasingly valuable in biological and chemical research. Currently, the most widely used organoid model in BC research is the patient-derived organoid (PDO) model, which is generated directly from original tumor tissues. This paper aims to summarize the current status of PDO models across various BC subtypes, highlighting recent advances in genetics, mechanisms of drug resistance, identification of new therapeutic targets, and approaches to personalized treatment. In conclusion, the development of clinical precision medicine urgently requires in vitro models capable of accurately simulating the unique molecular subtypes of patients. This review will examine the challenges and future prospects of organoid models in BC research, offering new insights into the fundamental mechanisms of BC and paving the way for more effective personalized therapies
Comprehensive exosomal microRNA profile and construction of competing endogenous RNA network in autism spectrum disorder: A pilot study
Get PDFExosomes have been demonstrated to exert momentous roles in autism spectrum disorder (ASD). However, few studies have reported a correlation between exosomal microRNAs (miRNAs) and ASD. To date, our understanding of crucial competing endogenous RNA (ceRNA) networks in ASD remains limited. Herein, the exosomal miRNA profile in the peripheral blood of children with ASD and healthy controls was investigated and the level of immune cell infiltration in ASD was evaluated to determine the distribution of immune cell subtypes. Exosomes were isolated from the peripheral blood of ten children with ASD and ten healthy controls, and further identified using transmission electron microscopy and western blot analysis. RNA sequencing was conducted to investigate exosomal miRNA profiles in patients with ASD. The mRNA and circular RNA (circRNA) expression profiles were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified and ceRNA regulatory networks were constructed. Furthermore, the immune cell infiltration levels in patients with ASD were evaluated. Exosomes were spherical, approximately 100 nm in size, and were confirmed via western blot analysis using exosome-associated markers CD9, CD63, and CD81. Thirty-five DEmRNAs, 63 DEmiRNAs, and 494 DEcircRNAs were identified in patients with ASD. CeRNA regulatory networks, including 6 DEmRNAs, 14 DEmiRNAs, and 86 DEcircRNAs, were established. Correlation analysis indicated that leucine-rich glioma inactivated protein 1 (LGI1) expression was significantly positively correlated with the content of CD8+ T cells. Our findings may be conducive to offering novel insights into this disease and providing further evidence of transcriptomic abnormalities in ASD
The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders
Get PDFMarfan syndrome (MFS) is a multisystem genetic disorder with over 3000 mutations described in the fibrillin 1 (FBN1) gene. Like MFS, other connective tissue disorders also require a deeper understanding of the phenotype-genotype relationship due to the complexity of the clinical presentation, where diagnostic criteria often overlap. Our objective was to identify mutations in patients with connective tissue disorders using a genetic multipanel and to analyze the genotype-phenotype associations in a cohort of Mexican patients. We recruited 136 patients with MFS and related syndromes from the National Institute of Cardiology. Mutations were identified using next-generation sequencing (NGS). To examine the correlation between mutation severity and severe cardiovascular conditions, we focused on patients who had undergone Bentall-de Bono surgery or aortic valve repair. The genetic data obtained allowed us to reclassify the initial clinical diagnosis across various types of connective tissue disorders. The transforming growth factor beta receptor 2 (TGFBR2) rs79375991 mutation was found in 10 out of 16 (63%) Loeys-Dietz patients. We observed a high prevalence (65%) of more severe mutations, such as frameshift indels and stop codons, among patients requiring invasive treatments like aortic valve-sparing surgery, Bentall and de Bono procedures, or aortic valve replacement due to severe cardiovascular injury. Although our study did not achieve precise phenotype-genotype correlations, it underscores the importance of a multigenetic panel evaluation. This could pave the way for a more comprehensive diagnostic approach and inform medical and surgical treatment decision-making
Development and validation of a diagnostic model to differentiate spinal tuberculosis from pyogenic spondylitis by combining multiple machine learning algorithms
Get PDFThis study focused on the development and validation of a diagnostic model to differentiate between spinal tuberculosis (STB) and pyogenic spondylitis (PS). We analyzed a total of 387 confirmed cases, out of which 241 were diagnosed with STB and 146 were diagnosed with PS. These cases were randomly divided into a training group (n = 271) and a validation group (n = 116). Within the training group, four machine learning (ML) algorithms (least absolute shrinkage and selection operator [LASSO], logistic regression analysis, random forest, and support vector machine recursive feature elimination [SVM-RFE]) were employed to identify distinctive variables. These specific variables were then utilized to construct a diagnostic model. The model’s performance was subsequently assessed using the receiver operating characteristic (ROC) curves and the calibration curves. Finally, internal validation of the model was undertaken in the validation group. Our findings indicate that PS patients had an average platelet-to-neutrophil ratio (PNR) of 277.86, which was significantly higher than the STB patients’ average of 69.88. The average age of PS patients was 54.71 years, older than the 48 years recorded for STB patients. Notably, the neutrophil-to-lymphocyte ratio (NLR) was higher in PS patients at 6.15, compared to the 3.46 NLR in STB patients. Additionally, the platelet volume distribution width (PDW) in PS patients was 0.2, compared to 0.15 in STB patients. Conversely, the mean platelet volume (MPV) was lower in PS patients at an average of 4.41, whereas STB patients averaged 8.31. Hemoglobin (HGB) levels were lower in PS patients at an average of 113.31 compared to STB patients\u27 average of 121.64. Furthermore, the average red blood cell (RBC) count was 4.26 in PS patients, which was less than the 4.58 average observed in STB patients. After evaluation, seven key factors were identified using the four ML algorithms, forming the basis of our diagnostic model. The training and validation groups yielded area under the curve (AUC) values of 0.841 and 0.83, respectively. The calibration curves demonstrated a high alignment between the nomogram-predicted values and the actual measurements. The decision curve indicated optimal model performance with a threshold set between 2% and 88%. In conclusion, our model offers healthcare practitioners a reliable tool to efficiently and precisely differentiate between STB and PS, thereby facilitating swift and accurate diagnoses
Raised levels of chemerin in women with preeclampsia: A meta-analysis
Get PDFChemerin is a multifunctional adipokine associated with systemic inflammation, angiogenesis, and oxidative stress. Emerging evidence suggests a potential link between chemerin and the pathogenesis of preeclampsia (PE). In this systematic review and meta-analysis, we aimed to evaluate the serum chemerin levels in women with PE. A systematic search was conducted across Medline, Web of Science, and Embase databases from inception until April 15, 2023, to identify studies comparing serum chemerin levels in pregnant women with and without PE. A random-effects model was employed to pool the results, accounting for heterogeneity. Thirteen datasets from 10 observational studies, encompassing 832 women with PE and 1298 healthy pregnant women, were analyzed. The pooled findings indicated a statistically significant elevation in serum chemerin levels in women with PE compared to controls (mean difference [MD] = 89.56 ng/mL, 95% confidence interval [CI] 62.14 - 116.98; P < 0.001; I2 = 87%). The subgroup analysis revealed consistent findings across studies that measured chemerin levels before or after the diagnosis of PE, studies that did or did not match the body mass index (BMI), and studies with varying quality scores (P values for subgroup differences were all > 0.05). Compared to controls, women with severe PE exhibited a significantly greater increase in serum chemerin levels than those with mild PE (P value for subgroup difference = 0.007). Additionally, meta-regression analysis results suggested that the mean BMI of the included pregnant women might positively modify the difference in circulating chemerin levels between women with and without PE (coefficient = 8.92; P = 0.045). In conclusion, this meta-analysis suggests a positive correlation between elevated serum chemerin levels and PE diagnosis in comparison to pregnant women without the condition
Urinary ATP may be a biomarker of interstitial cystitis/bladder pain syndrome and its severity
Get PDFUrinary tract cells respond to bladder distension by releasing adenosine triphosphate (ATP). Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) exhibit elevated urinary ATP levels compared to asymptomatic controls. This study aimed to evaluate the potential of urinary ATP as a non-invasive biomarker for IC/BPS and its correlation with symptom severity. We included 56 patients diagnosed with IC/BPS and 50 asymptomatic controls. Urine samples were collected from both groups. Urinary ATP levels were quantified using the luciferin-luciferase bioluminescence method. The severity of IC/BPS symptoms was assessed using the visual analogue score (VAS), Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI) from the O\u27Leary-Sant score. We specifically examined the correlation between symptom scores and urinary ATP levels in IC/BPS patients. Urinary ATP levels were significantly higher in IC/BPS patients compared to the control group (P < 0.0001). There was a significant positive correlation between urinary ATP concentrations and VAS, ICPI, and ICSI scores among IC/BPS patients (P < 0.0001). The threshold value for ATP concentration was set at 56.6 nM, with an area under the receiver operating characteristic (ROC) curve of 0.811 (95% CI 0.730 - 0.892). Our findings indicate that IC/BPS patients excrete elevated amounts of ATP in their urine. This suggests that urinary ATP might serve as a non-invasive biomarker for IC/BPS, with a predictive potential in terms of symptom severity