Search Results (34)

Background/Objectives: This study investigated the relationship between glycemic control and increased glomerular filtration rate (eGFR), as assessed by serum creatinine and the CKiD equation in children and adolescents with T1DM. Methods: This cross-sectional observational study involved 80 T1DM patients (4–19 years) attending the Interdisciplinary Center for Diabetes. Biochemical, anthropometric, and skeletal muscle mass parameters were evaluated. The GFR was estimated using the CKiD equation expressed in mL/min/1.73 m². Results: Our results showed that nearly 19.0% of the included patients presented increased values for eGFR, and most had poor glycemic control. Patients with HbA1c levels above 8% presented eGRF > 130. There was a positive correlation between hyperglycemia, elevated HbA1c, and fat percentage with higher eGRF values. In addition, the reduction in lean mass and skeletal muscle mass was related to elevated eGRF. Conclusions: Our study indicates that children and adolescents with T1DM who have elevated HbA1c, lower lean mass, and less than five years of diagnosis of diabetes are more likely to present higher eGRF values. Full article

Background: Casein kinase I-like (CKL) protein is a member of the serine/threonine kinase CKI family and plays a pivotal regulatory role in various eukaryotic cellular processes, including stress responses. Objectives: This study aims to systematically identify the CKL gene family in the tomato genome and investigate its responsiveness to abiotic stress. Methods: Members of SlCKL were identified through genome-wide bioinformatics analysis, and their physicochemical properties, chromosomal localization, gene structure, conserved domains, phylogenetic relationships, cis-acting elements, cross-species collinearity, and tissue expression profiles were comprehensively analyzed. The expression patterns of SlCKL genes under abiotic stress were validated using real-time quantitative PCR. Results: A total of 16 SlCKL genes were identified and classified into three subfamilies (I–III), which are unevenly distributed across nine chromosomes, predominantly clustered at the ends. The gene structure, motifs, and functional domains exhibit high conservation. Collinearity analysis revealed stronger synteny between tomato and Arabidopsis thaliana or pepper compared to rice, maize, or tobacco, suggesting a common ancestral origin. The tissue expression profile indicates that SlCKLs are preferentially transcribed in roots. Promoter analysis and qRT-PCR validation demonstrated differential responses of SlCKLs to various abiotic stresses, such as drought, salt, heat, cold, and ABA treatment. Conclusions: This study represents the first systematic identification of the tomato SlCKL gene family, elucidating its evolutionary relationships, structural characteristics, tissue-specific expression patterns, and differential responsiveness to abiotic stress, thereby providing a critical foundation for further investigation into the molecular mechanisms underlying CKL-mediated abiotic stress adaptation in tomatoes. Full article

Background: While early risk stratification in STEMI is essential, the threat of cardiogenic shock (CS) persists after revascularization due to reperfusion injury and evolving instability. However, risk prediction in later phases—after revascularization—is less explored, despite its importance in guiding intensive care decisions. This study evaluates machine learning (ML) models for dynamic risk assessment in interventional cardiology and cardiac intensive care unit (CICU) phases, where timely detection of deterioration can guide treatment escalation. Methods: We retrospectively analyzed clinical and procedural data from 158 patients diagnosed with STEMI complicated by cardiogenic shock, treated between 2019 and 2022 at the Cardiology Department of the University Emergency Hospital of Bucharest, Romania. Machine learning models—Random Forest (RF), and Quadratic Discriminant Analysis (QDA)—were developed and tested specifically for the interventional cardiology and CICU phases. Model performance was evaluated using area under the receiver operating characteristic curve (ROC-AUC), accuracy (ACC), sensitivity, specificity, and F1-score. Results: In the interventional phase, RF and QDA achieved the highest accuracy, both reaching 87.50%. In the CICU, RF and QDA demonstrate the best performance, reaching ACCs of 0.843. QDA maintained consistent performance across phases. Relevant predictors included reperfusion strategy, TIMI flow before percutaneous coronary intervention (PCI), Killip class, creatinine, and Creatine Kinase Index (CKI)—all parameters routinely assessed in STEMI patients. These models effectively identified patients at risk for post-reperfusion complications and hemodynamic decline, supporting decisions regarding extended monitoring and ICU-level care. Conclusions: Predictive models implemented in advanced STEMI phases can contribute to dynamic, phase-specific risk reassessment and optimize CICU resource allocation. These findings support the integration of ML-based tools into post-PCI workflows, enabling earlier detection of clinical decline and more efficient deployment of intensive care resources. When combined with earlier-stage models, the inclusion of interventional and CICU phases forms a dynamic, end-to-end risk assessment framework. With further refinement, this system could be implemented as a mobile application to support clinical decisions throughout the STEMI care continuum. Full article

Background: Guidelines recommend switching the glomerular filtration rate (eGFR) estimation from the CKiD-U25 to the CKD-EPI formula at age 18. We investigated how this would affect chronic kidney disease (CKD) classification. Methods: Serum creatinine was enzymatically measured in 1061 samples from 914 community-based 10–23-year-olds from Tlaxcala, Mexico, a region where urinary biomarkers demonstrated early kidney damage associated with exposure to inorganic toxins in a pediatric population. We calculated their eGFR using CKiD-U25, modified Schwartz, the first and modified Pottel full-age spectrum (FAS), and CKD-EPI formulae. Correlation analysis characterized the CKD stage stratified by age and sex. Results: At baseline, the median age was 13 (IQR: 12, 15) years, and 55% were female. Median CKiD-U25 eGFR was 96.9 (IQR: 83.3, 113.3) mL/min/1.73 m², significantly lower than the CKD-EPI eGFR, which was 140.8 (IQR: 129.9, 149.3) mL/min/1.73 m² (p < 0.0001, Wilcoxon rank test). The mean bias was 36.99 ± 12.89 mL/min/1.73 m². Pearson correlation was r = 0.8296 (95% confidence interval 0.0898–0.8474). There was a better correlation between the modified Schwartz (r = 0.9421 (0.9349, 0.9485)) and the Pottel FAS (r = 0.9299 (0.9212, 0.9376)) formulae. Agreement was deficient when the eGFR was >75 mL/min/1.73 m² in younger age and female sex. Modified Schwartz identified 281 (26.4%) measurements as having CKD 2 and 3 (2+), U25 identified 401 (37.7%) measurements as having CKD 2+, FAS identified 267 (25.1%) and modified FAS identified 282 (30%) measurements as having CKD 2+, and CKD-EPI identified 51 (4.8%) measurements as having CKD 2+, respectively. Conclusions: In this population, there needed to be better agreement between the various eGFR formulae. CKD-EPI identifies substantially fewer at-risk participants as having CKD. Full article

Low temperature stress represents a significant abiotic stress factor affecting rice yields. While the structure and some of the functions of cell cycle protein-dependent protein kinase inhibitor (CKI) family proteins have been the subject of study, their relevance to cold tolerance in rice has been less investigated. In this study, we cloned OsEL2 (LOC_Os03g01740) and constructed anti-expression lines of this gene. The resulting lines exhibited significant cold sensitivity and displayed greater oxidative damage than wild type Nippobare (Nip). However, the activities of antioxidant enzymes, such as catalase (CAT), were significantly elevated in OsEL2-AX plants in comparison to Nip following exposure to 4 °C stress. RNA sequencing revealed the presence of 18,822 differential genes, with the majority of them being expressed with temporal specificity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that a considerable number of differentially expressed genes (DEGs) are involved in the metabolism of amino acids, lipids, and terpenoids. Weighted gene co-expression network analysis (WGCNA) revealed a close relationship between the genes in the turquoise and light green modules and rice cold tolerance traits. These genes were predominantly enriched in terpene metabolism and the metabolism of various plant secondary metabolites, suggesting that OsEL2 influences rice cold tolerance through the metabolism of these two classes of substances. An analysis of the genes within these two modules using transcription factor (TF) enrichment and KEGG enrichment revealed that they are predominantly regulated by mitogen-activated protein kinase (MAPK) and ethylene signaling pathways. Furthermore, we found that tryptophan metabolism, phenylalanine metabolism, and monoterpene synthesis were enriched in down-regulated pathway enrichment analysis. In addition, we also found that the MAPK signaling pathway was enriched in the KEGG enrichment analysis of AX2 with Nip. The results demonstrate that anti-expression of OsEL2 is associated with a notable decline in rice tolerance to cold stress. Full article

Background: Sarcopenia, characterized by the loss of skeletal muscle mass, is an emerging comorbidity associated with poor outcomes in cardiovascular surgery. Its impact on mortality in patients undergoing valve surgery for infective endocarditis (IE) remains underexplored. This study investigates the relationship between sarcopenia, measured by the Psoas muscle area index (PMAi), and mortality in patients with IE undergoing valve surgery. Materials and Methods: We retrospectively analyzed 68 patients with IE who underwent valve surgery at a tertiary care center from 2013 to 2021. Sarcopenia was defined as being in the lowest quartile of PMAi, measured via preoperative computed tomography (CT). Baseline characteristics, survival outcomes, and factors influencing mortality were analyzed using Kaplan–Meier survival curves and Cox proportional hazards regression. The predictive value of PMAi for 1-year and 3-year mortality was assessed via receiver operating characteristic (ROC) curves. Results: Sarcopenia was strongly associated with increased mortality at both 1-year (HR: 0.378, p = 0.010) and 3-year follow-ups (HR: 0.457, p = 0.012). Female sex (OR: 275.748, p < 0.001) and older age (OR: 9.995, p = 0.003) were significant predictors of sarcopenia. Chronic kidney insufficiency (CKI) and the use of heart failure medication therapy also significantly impacted survival outcomes. Conclusions: Sarcopenia is a strong independent predictor of short- and mid-term mortality in patients undergoing valve surgery for IE. Routine radiological assessment of sarcopenia using PMAi could improve risk stratification and guide preoperative interventions. Tailored management strategies, especially in older women and patients with CKI, may enhance outcomes in this high-risk population. Full article

Background: Compound Ku-Shen Injection (CKI) is a traditional Chinese medicine preparation derived from Ku-Shen and Bai-Tu-Ling, commonly used in the adjunctive treatment of advanced cancers, including liver cancer. However, the underlying mechanisms of CKI’s effectiveness in cancer treatment are not well defined. Methods: This study employs network pharmacology to investigate the traditional Chinese medicine (TCM) compatibility theory underlying CKI’s action in treating liver cancer, with findings substantiated by molecular docking and in vitro experiments. Sixteen active components were identified from CKI, along with 193 potential targets for treating liver cancer. Key therapeutic target proteins, including EGFR and ESR1, were also identified. KEGG enrichment results showed that the neuroactive ligand–receptor interaction, cAMP signaling pathway, and serotonergic synapses make up the key pathway of CKI in the treatment of liver cancer. Molecular docking results confirmed that the key active ingredients effectively bind to the core targets. CCK-8 cytotoxic experiment results show that the CKI key components of oxymatrine and matrine can inhibit the growth of HepG2 liver cancer cell proliferation. A Western blot analysis revealed that oxymatrine suppresses the expression of EGFR, contributing to its therapeutic efficacy against liver cancer. Conclusion: our study elucidated the therapeutic mechanism of CKI in treating liver cancer and unveiled the underlying principles of its TCM compatibility through its mode of action. Full article

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at “Louis Turcanu” Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT. Full article

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008–2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations. Full article

This study investigated the effects of substituting B with FR and UVA (50 μmol·m⁻²·s⁻¹) at two growth stages on the growth and quality of loose-leaf lettuce (cv. Fangni). The basal light was red and blue LEDs at 250 μmol·m⁻²·s⁻¹. At stage I (the first 10 days of 20-day pre-harvest), there were three treatments: B substituted by FR (FR); B substituted by UVA (UVA); and no substituting (CKI). At stage II (next ten days after stage I), there were 9 treatments: FF (FR + FR), UF (UVA + FR), BF (B + FR), FU (FR + UVA), UU (UVA + UVA), BU (B + UVA), FB (FR + B), UB (UVA + B), and B + B (CKII). At stage I, compare with UV-A and CKI, the shoot fresh weight, leaf area, leaf width, leaf length, and vitamin C content highly increased under far-red light (FR), whereas specific leaf weight and the chlorophyll contents significantly decreased by FR. In CKI, nitrate contents and the antioxidant capacity (FRAP, DPPH) were significantly higher than in FR and UVA. At stage II, higher leaf width, leaf length, leaf area, and shoot fresh and dry weight were observed in FF, UF, and BF. The lowest biomass was shown in CKII. Higher chlorophyll contents were found in FU and FB. The soluble sugar contents significantly increased by all treatments. In addition to UB and BU, soluble protein contents increased by other treatments. There were higher vitamin C contents in UU, UB, and CKII. Large amounts of nitrates accumulated under CKII. The higher antioxidant capacity (DPPH, FRAP) was found in FB and CKII. The highest flavonoid content was found in UB, and higher polyphenols contents were found in UB and BU. In this study, substituting B with FR at 2 stages were the best way to increase lettuce biomass. The optimal measure to both increased lettuce nutrition quality and biomass was FB at stage II. Full article

Multi-component drugs (MCDs) can induce various cellular changes covering multiple levels, from molecular and subcellular structure to cell morphology. A “non-invasive” method for comprehensively detecting the dynamic changes of cellular fine structure and chemical components on the subcellular level is highly desirable for MCD studies. In this study, the subcellular dynamic processes of gastric cancer BGC823 cells after treatment with a multi-component drug, Compound Kushen Injection (CKI), were investigated using a homemade, high-resolution, confocal Raman spectroscopy (RS) device combined with bright-field imaging. The Raman spectra of the nucleus, cytoplasm and intracellular vesicles (0.4–1 μm) were collected simultaneously for each cell treated with CKI at different times and doses. The RS measurements showed that CKI decreased the DNA signatures, which the drug is known to inhibit. Meanwhile, the CKI-induced subcellular dynamic changes in the appearance of numerous intracellular vesicles and the deconstruction of cytoplasm components were observed and discussed. The results demonstrated that high-resolution subcellular micro-Raman spectroscopy has potential for detecting fine cellular dynamic variation induced by drugs and the screening of MCDs in cancer therapy. Full article

We aimed to evaluate the predictive and prognostic value of baseline ¹⁸F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy–chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into “responder” (n = 33) and “non-responder” (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for “PET-Skewness” and 0.75 predicting overall progression for “PET-Median”. In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06–0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11–0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy. Full article

Apples are a major horticultural crop worldwide. Grafting techniques are widely utilized in apple production to keep the varieties pure. Interstocks are frequently used in Northern China to achieve intensive apple dwarfing cultivation. High-throughput sequencing was used to investigate differentially expressed genes in the phloem tissues of two different xenograft systems, M (‘Gala’/‘Mac 9’/Malus baccata (L.) Borkh.) and B (‘Gala’/Malus baccata (L.) Borkh.). The results showed that dwarfing interstocks could significantly reduce the height and diameters of apple trees while have few effects on the growth of annual branches. The interstocks were found to regulate the expression of genes related to hormone metabolism and tree body control (GH3.9, PIN1, CKI1, ARP1, GA2ox1 and GA20ox1), these effects may attribute the dwarf characters for apple trees with interstocks. Besides, the interstocks reduce photosynthesis-related genes (MADH-ME4 and GAPC), promote carbon (C) metabolism gene expression (AATP1, GDH and PFK3), promote the expression of nitrogen (N)-metabolism-related genes (NRT2.7, NADH and GDH) in rootstocks, and improve the expression of genes related to secondary metabolism in scions (DX5, FPS1, TPS21 and SRG1). We also concluded that the interstocks acquired early blooming traits due to promotion of the expression of flowering genes in the scion (MOF1, FTIP7, AGL12 and AGL24). This study is a valuable resource regarding the molecular mechanisms of dwarf interstocks’ influence on various biological processes and transplantation systems in both scions and rootstocks. Full article

Verbena officinalis L. or vervain is an herbal medicine and dietary supplement used worldwide. It is used for antidepressant and anticonvulsant purposes, as well as to treat inflammatory disorders, skin burns, abrasions, and gastric diseases, among others. Here, we investigated the biochemical, antioxidant, and histopathological effects of vervain against chronic physical stress. Male Wistar rats were submitted to chronic physical training and oral administration of 200 mg/kg of extract for 7 weeks. Control animals were not treated with either stress or vervain. Body weight was monitored during the study. Liver, kidney, spleen, testis, epididymis, heart, skeletal muscle, and brain samples were collected. Blood cholesterol, lactate dehydrogenase (LDH), bilirubin, and creatinine kinase (CREA), among others, were studied. Glutathione peroxidase (GPox) and superoxide dismutase (SOD) antioxidant activity was analyzed in the blood, liver, and kidney. Testosterone measurements were also performed on whole testis extracts. We found significant weight ratios differences in the epididymis, brain, and heart. Animals submitted to training showed hemorrhagic livers. Kidney histology was affected by both stress and vervain. Cell disruption and vacuolization were observed in the testes and epididymis of animals submitted to stress. Hematological and biochemical markers as CREA, LDH, TP, CKI, URCA, γGT, and glucose revealed statistically significantly differences. Additionally, the activity of glutathione peroxide (GPox) and superoxide dismutase (SOD) in the blood was also impacted. Both stress and vervain have significant in vivo effects. Infusions of vervain include phenylpropanoids, iridoids, verbenalin, hastatoside, and flavonoids, amongst others, which interact synergistically to produce the preclinical effects reported here. Full article

Kinase-targeted drug discovery for cancer therapy has advanced significantly in the last three decades. Currently, diverse kinase inhibitors or degraders have been reported, such as allosteric inhibitors, covalent inhibitors, macrocyclic inhibitors, and PROTAC degraders. Out of these, covalent kinase inhibitors (CKIs) have been attracting attention due to their enhanced selectivity and exceptionally strong affinity. Eight covalent kinase drugs have been FDA-approved thus far. Here, we review current developments in CKIs. We explore the characteristics of the CKIs: the features of nucleophilic amino acids and the preferences of electrophilic warheads. We provide systematic insights into privileged warheads for repurposing to other kinase targets. Finally, we discuss trends in CKI development across the whole proteome. Full article