Biomolecules & biomedicine最新文献

This study aims to evaluate the clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging (CEUS-MFI) in the differential diagnosis of benign and malignant renal tumors. All patients underwent CEUS, MFI, color doppler flow imaging (CDFI), and CEUS-MFI. The efficacies of these different diagnostic modalities in diagnosing benign and malignant renal tumors were evaluated by Kappa consistency test and the receiver operating characteristic (ROC) curve, with pathological findings serving as the gold standard. CDFI, MFI and CEUS-MFI all demonstrated higher blood flow in malignant tumors compared with benign tumors. Compared with benign tumors, CDFI detected a higher rate of punctate and linear Adler grade 2 and 3 blood flows in malignant tumors, as well as peripheral semicircular or annular blood flow. MFI identified a high rate of peripheral circumferential blood flow and irregular vascular morphology in malignant tumors, with most exhibiting Adler grade 3 blood flow. In addition, CEUS-MFI showed more dendritic or irregular Adler grade 2 or 3 blood flows in malignant renal tumors than MFI alone. Further analysis showed that CEUS-MFI had the highest consistency with pathological diagnosis (Kappa = 0.808). The ROC curve showed that the area under the curve (AUC) for CEUS-MFI in differentiating between benign and malignant lesions was 0.898, significantly outperforming other single diagnostic methods. With its capability to display microvascular information and assess overall pathological characteristics, MFI can accurately predict the nature of renal tumors and assist in surgical planning.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important underlying cause of morbidity and mortality in patients with CTD. Serum Krebs von den Lungen-6 (KL-6) is an immune factor which has been related to the severity of ILD. This systematic review and meta-analysis aimed to evaluate the association between serum KL-6 and mortality of patients with CTD-ILD. Longitudinal studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Fifteen cohorts involving 1737 patients with CTD-ILD were included. During a mean follow-up of 35.3 months, 430 (24.8%) patients died. Compared to those with a lower KL-6 at admission, patients with a higher KL-6 were associated with a higher mortality risk during follow-up (risk ratio: 2.18, 95% confidence interval: 1.66 to 2.87, P < 0.001; I2 = 20%). Subgroup analysis showed a significant association in studies from Asian countries, but not in those from non-Asian countries; in studies with cutoff of KL-6 derived in receiver operating characteristic (ROC) curve analysis, but not in those derived from other methods; in studies with multivariate analysis, but not in those with univariate analysis (P for subgroup difference all < 0.05). The association was not significantly affected by different CTDs or methods for measuring serum KL-6. In conclusion, a high serum KL-6 may be a risk factor of increased mortality in patients with CTD-ILD.

Dear Editor, In relation to the letter expressing concerns about some important points of the article entitled "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", we would like to comment on the following.  Read more in the PDF.

General anesthesia (GA) is typically recommended for category 1 emergency cesarean delivery (CD). For categories 2-4 emergencies, either regional or GA can be used. The factors influencing the choice of anesthetic technique in these categories remain poorly understood. We analyzed the association between the type of labor analgesia and subsequent anesthetic techniques employed for intrapartum categories 2 and 3 CD. In a prospective longitudinal cohort study, 300 women were consequently enrolled and categorized according to Lucas's classification of CD urgency. The techniques of anesthesia (GA, spinal, and epidural anesthesia [EA]) employed for CD were analyzed with respect to labor analgesia methods (remifentanil patient-controlled analgesia [remifentanil-PCA], EA, and nitrous oxide [N2O]). EA was the most frequent analgesic option (43.8%), followed by remifentanil-PCA (20.7%) and N2O (5.1%), while 30.4% of parturient women received no analgesia. All anesthetic methods showed a significant relationship with analgesic modalities (P < 0.001). Remifentanil-PCA was associated with a higher incidence of GA. Contraindication to EA was the primary factor related to the transition from remifentanil-PCA to GA. Most parturients who received EA were successfully converted to EA. Spinal anesthesia was the most common technique in women using N2O and those without labor analgesia. GA was associated with lower 5-min Apgar scores. The method of labor analgesia was associated with the anesthesia technique employed for categories 2 and 3 CD. This finding may guide patient counseling and intrapartum anesthetic planning. However, the analysis should be cautiously interpreted as the selection of anesthesia is a complex decision influenced by several clinical considerations.

Klebsiella pneumoniae, a member of the Enterobacteriaceae family, demonstrates an increasing trend of resistance to carbapenems and is a common cause of both hospital- and community-acquired infections. The current study provides insights into the genetic characterization of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates circulating during 2022 in a Sarajevo tertiary hospital. Among the 87 CRKP strains analyzed, real-time polymerase chain reaction (rtPCR) results showed that 85 (97.7%) tested positive for the carbapenem resistance gene. The oxacillinase-48 (OXA-48) gene was detected in 83 (95.4%) isolates, while the Klebsiella pneumoniae carbapenemase (KPC) and the New Delhi metallo-beta-lactamase (NDM) genes were detected in one isolate each. No Verona integron-encoded-metallo-beta-lactamase (VIM) or imipenemase-metallo-beta-lactamase 1 (IMP-1) genes were found in any of the tested isolates. The multilocus sequence typing (MLST) analysis of sequence types (STs) revealed that ST101, an emerging high-risk clone exhibiting extensive drug resistance, was the most prevalent, whereas ST307 was detected in only one isolate. Phylogenetic analysis of the ten CRKP isolates indicated the presence of three clusters that could constitute an outbreak. A comparison of the results of the utilized phenotypic test (the combined-disk test [CDT]) and rtPCR showed high concordance, suggesting that the phenotypic assay may be useful for the early detection of resistance mechanisms as part of routine susceptibility testing. With the increased affordability of next-generation sequencing (NGS), its application in hospital settings has proven highly beneficial, aiding in the implementation of infection control and prevention measures. Given the significant resistance demonstrated by the CRKP isolates to most tested antibiotics, it is imperative to establish effective methods to restrict the spread of these isolates, as well as to carefully monitor the use of carbapenems in clinical practice.

The objective of this research was to investigate the potential mechanisms of AlkB homolog 5, RNA demethylase (ALKBH5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas (TCGA), Kruskal-Wallis method and Kaplan-Meier (KM) survival analysis to study the expression of ALKBH5 and its correlation with clinical factors in HCC. In vitro experiments verified the expression of ALKBH5 and its effect on HCC cell phenotype. We screened differentially expressed genes (DEGs) from HCC patients associated with ALKBH5. Through this screening we identified the downstream gene TTI1 which is associated with ALKBH5 and investigated its function using Gene Expression Profiling Interaction Analysis (GEPIA) along with univariate Cox proportional hazards regression analysis. Finally, we analyzed the functions of ALKBH5 and TTI1 in HCC cells. Across numerous pan-cancer types, we observed significant overexpression of ALKBH5. In vitro experiments confirmed ALKBH5 as an oncogene in HCC, with its knockdown leading to suppressed cell proliferation, migration, and invasion. Bioinformatics analyses also demonstrated a significant positive correlation between ALKBH5 and TTI1. TTI1, highly expressed in cells, showed promising prognostic ability for patients. Further experiments confirmed that suppressing TTI1 impeded cell growth and movement, with this effect partially offset by increased ALKBH5 expression. Conversely, promoting these cellular processes was observed with TTI1 overexpression, but was dampened by decreased ALKBH5 expression. In conclusion, our findings suggest that ALKBH5 may influence proliferation, migration and invasion of HCC by modulating TTI1 expression, providing a new direction for treating HCC.

Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease. We investigated the relationship of peripheral blood long noncoding RNA-plasmacytoma variant translocation 1 (lncRNA-PVT1) and microRNA (miR)-146a levels with Th17/Treg-related cytokines in HT patients and their clinical significance. Correlations of PVT1 and miR-146a with Th17/Treg-related cytokines were analyzed, and its clinical value in diagnosing HT was assessed. Results showed reduced lncRNA-PVT1 and interleukin (IL)-10 levels and increased miR-146a and IL-17 levels in HT patients. lncRNA-PVT1 negatively interrelated with miR-146a, IL-17, IL-23 and IL-6, and positively interrelated with IL-10; miR-146a positively correlated with IL-17, IL-23 and IL-6, but negatively correlated with IL-10 in HT patients. The area under the curve (AUC) of lncRNA-PVT1 and miR-146a levels for diagnosing HT were 0.822 and 0.844, respectively (sensitivity 88.73% and 86.62%, specificity 67.02% and 69.15%, cut-off values 0.76 and 2.73), with their combined detections yielding a higher AUC. Patients with poorly expressed lncRNA-PVT1 and highly expressed miR-146a had elevated HT incidence. lncRNA-PVT1 and miR-146a levels were also found to be an independent influencing factor for HT occurrence. Our findings suggest that HT patients have low peripheral blood lncRNA-PVT1 expression and high miR-146a expression. lncRNA-PVT1 and miR-146a level changes were correlated with Th17/Treg cytokine imbalance and could be a potential diagnostic tool and independent influencing factor for HT.

Radiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications.

Glomerular hyperfiltration (GHF) is an early marker of chronic kidney disease (CKD) and may predict coronary microvascular dysfunction, presenting as reduced coronary flow velocity reserve (CFVR) in patients with a history of gestational diabetes (GDM). This study aimed to assess the glomerular filtration rate (GFR) and compare CFVR in patients with a history of GDM. We screened patients referred to the Cardiology Department of Istanbul Medeniyet University for angina pectoris, excluding those with positive treadmill test results. Women with a history of GDM were categorized into three groups based on GFR levels: Group 1 (60-89 ml/min), Group 2 (90-119 ml/min), and Group 3 (≥ 120 ml/min). Coronary diastolic peak velocities were measured at baseline and after dipyridamole administration, with CFVR defined as the ratio of hyperemic to baseline diastolic peak velocities. The homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index were derived from patient files. A total of 166 patients were included: 57 in Group 1, 80 in Group 2, and 29 in Group 3. HOMA-IR was higher in Group 3 compared to Group 2 (P < 0.05). Group 1 had the lowest CFVR (2.3 ± 0.3%), Group 2 had the highest (2.5 ± 0.3%), and Group 3 showed a moderate decrease in CFVR (2.4 ± 0.3%). Multivariate linear regression analysis revealed that HbA1c was independently associated with CFVR. In patients with GDM, GHF is associated with reduced CFVR, linked to metabolic parameters such as HbA1c and HOMA-IR. Interventions to improve metabolic health may prevent cardiovascular disease in these patients.