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INTRODUCTION: Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. METHODS: This study is a secondary dataset analysis of cross-sectional data from theKorea National Health and Nutrition Examination Survey (KNHANES) 2016- 2019. We included 1450 participants aged 65-79 years, excluding those who had never smoked. Dynapenia was defined as grip strength <28 kg for men and <18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression analysis evaluated the association between smoking cessation and dynapenia. RESULTS: Compared with current smokers, the adjusted odds ratio (AOR) of dynapenia in former smokers was 0.66 (95% CI: 0.44-0.99). The AORs for smoking cessation periods of ≤10 years, 10-20 years, 20-30 years, and >30 years were 0.67 (95% CI: 0.39-1.16), 0.61 (95% CI: 0.36-1.03), 0.65 (95% CI: 0.37-1.14), and 0.52 (95% CI: 0.25-1.06), respectively. The AOR for dynapenia significantly decreased with the years since smoking cessation (p for trend=0.043). CONCLUSIONS: Our findings suggest that smoking cessation can reduce the likelihood of dynapenia among older lifetime smokers, with a decreasing likelihood trend associated with longer cessation periods.
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Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from Morus alba. Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin's superior binding affinity to FAS, with a binding score of -7.3 kcal/mol compared to -6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.
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Células 3T3-L1 , Adipocitos , Adipogénesis , Diferenciación Celular , Simulación del Acoplamiento Molecular , Ratones , Animales , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Ácido Graso Sintasas/metabolismo , Ácido Graso Sintasas/antagonistas & inhibidores , PPAR gamma/metabolismo , PPAR gamma/genética , Metabolismo de los Lípidos/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , 4-Butirolactona/análogos & derivadosRESUMEN
BACKGROUND: Transposable elements (TEs) are known to be inserted into genome to create transcript isoforms or to generate long non-coding RNA (lncRNA) sequences. The insertion of TEs generates a gene protein sequence within the genome, but also provides a microRNA (miRNA) regulatory region. OBJECTIVE: To determine the effect of gene sequence changes caused by TE insertion on miRNA binding and to investigate the formation of an overlapping lncRNA that represses it. METHODS: The distribution of overlapping regions between exons and TE regions with lncRNA was examined using the Bedtools. miRNAs that can bind to those overlapping regions were identified through the miRDB web program. For TE-lncRNA overlapping genes, bioinformatic analysis was conducted using DAVID web database. Differential expression analysis was conducted using data from the GEO dataset and TCGA. RESULTS: Most TEs were distributed more frequently in untranslated regions than open reading frames. There were 30 annotated TE-lncRNA overlapping genes with same strand that could bind to the same miRNA. As a result of identifying the association between these 30 genes and diseases, TGFB2, FCGR2A, DCTN5, and IFI6 were associated with breast cancer, and HMGCS1, FRMD4A, EDNRB, and SNCA were associated with Alzheimer's disease. Analysis of the GEO and TCGA data showed that the relevant expression of miR-891a and miR-28, which bind to the TE overlapping region of DCTN5 and HMGCS1, decreased. CONCLUSION: This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.
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BACKGROUND: Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib. OBJECTIVE: To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib. METHODS: Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. In vivo studies were conducted using an epidermis-humanized transgenic mouse model and ex vivo human skin tissues. RESULTS: Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B-stimulated ex vivo human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes. CONCLUSION: Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.
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Background: To investigate the doctor shopping trend of patients with rotator cuff tear (RCT) before undergoing surgery and the relevance of the results to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000-5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with gender, age, VAS pain score immediately before surgery, or RCT size. Conclusions: Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.
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Honey bee (Apis mellifera L.) health is crucial for honey bee products and effective pollination, and it is closely associated with gut bacteria. Various factors such as reduced habitat, temperature, disease, and diet affect the health of honey bees by disturbing the homeostasis of the gut microbiota. In this study, high-throughput 16S rRNA gene sequencing was used to analyze the gut microbiota of honey bees subjected to seven diets over 5 days. Lactobacillus dominated the microbiota in all diets. Cage experiments (consumption, head protein content, and vitellogenin gene expression level) were conducted to verify the effect of the diet. Through a heatmap, the Diet2 (probiotic-supplemented) group was clustered together with the Beebread and honey group, showing high consumption (177.50 ± 26.16 mg/bee), moderately higher survival duration (29.00 ± 2.83 days), protein content in the head (312.62 ± 28.71 µg/mL), and diet digestibility (48.41 ± 1.90%). Additionally, we analyzed the correlation between gut microbiota and health-related indicators in honey bees fed each diet. Based on the overall results, we identified that probiotic-supplemented diets increased gut microbiota diversity and positively affected the overall health of individual honey bees.
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Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells (ICs) and IL-1ß/IL-6/TNF-α levels in the bronchoalveolar lavage fluid (BALF) and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2)/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of acute lung injury (ALI) mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1 (HO-1)/ NAD(P)H quinone dehydrogenase 1 (NQO1) in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.
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Euplotes baugilensis n. sp. was discovered in a temporary puddle that formed after rainfall on a mountain footpath near Gangneung-Wonju National University in Gangneung, South Korea. After isolation, a pure culture was established, and the new species was examined using live observation, silver-impregnation (protargol and 'wet' silver nitrate), scanning electron microscopy, and the analysis of the 18S rRNA gene sequence. Morphologically, E. baugilensis n. sp. is characterized by small body size (on average 49 × 31 µm in vivo), 9 ordinary fronto-ventral cirri (cirrotype-9) with one reduced cirrus V/2 (composed of four non-ciliated basal bodies), 5 transverse cirri, 7 or 8 dorsolateral kineties, 6 dorsal prominent ridges, and a dargyrome (silverline system) of double type. In this study, we have used a combination of morphological and molecular techniques to characterize E. baugilensis n. sp. and determine its phylogenetic position within the genus Euplotes. Molecular analysis using 18S rRNA gene sequences indicated that E. baugilensis n. sp. is most closely related to E. curdsi (with a sequence identity of 96.8 %).
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Phospholipid fatty acid (PLFA) analysis is used for characterizing microbial communities based on their lipid profiles. This method avoids biases from PCR or culture, allowing data collection in a natural state. However, PLFA is labor-intensive due to lipid fractionation. Simplified ester-linked fatty acid analysis (ELFA), which skips lipid fractionation, offers an alternative. It utilizes base-catalyzed methylation to derivatize only lipids, not free fatty acids, and found glycolipid and neutral lipid fractions are scarcely present in most bacteria, allowing lipid fractionation to be skipped. ELFA method showed a high correlation to PLFA data (r = 0.99) and higher sensitivity than the PLFA method by 1.5-2.57-fold, mainly due to the higher recovery of lipids, which was 1.5-1.9 times higher than with PLFA. The theoretical limit of detection (LOD) and limit of quantification (LOQ) for the ELFA method indicated that 1.54-fold less sample was needed for analysis than with the PLFA method. Our analysis of three bacterial cultures and a simulated consortium revealed the effectiveness of the ELFA method by its simple procedure and enhanced sensitivity for detecting strain-specific markers, which were not detected in PLFA analysis. Overall, this method could be easily used for the population analysis of synthetic consortia.
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BACKGROUND: Humeral component retroversion (HcRV) can be customized to match native humeral retroversion (RV) during reverse total shoulder arthroplasty (RTSA). However, assessing postoperative individualized HcRV using computed tomography (CT) scans without an elbow can be challenging. Therefore, we developed a new method to obtain the HcRV and evaluated its reliability. METHODS: A total of 106 patients underwent RTSA using a single implant, in which the humeral component was implanted based on the preoperative humeral RV (Pre_HRV) using a bilateral CT scan of the elbow. Intraoperatively, a retroversion guide with version hole at 10° intervals was used; Pre_HRV was converted to 5° increments and applied for humeral component implantation. The axis of intertubercular sulcus (ITS) was defined as the line perpendicular to the intertubercular line, and the angle between the axis of ITS and the trans-epicondylar axis was defined as the bicipital groove rotation (BGR). ITS orientation was defined as the angle between the axis of ITS and the central axis of the humeral head. Since the BGR does not change, the postoperative implanted HcRV (Post_HcRV)f is calculated as the BGR minus the value of the postoperative ITS orientation. An agreement analysis was performed between Post_HcRV and both the intraoperatively applied humeral RV (I_HRV) and Pre_HRV, as well as between the pre- and postoperative ITS orientations. The humeral component's insertional errors were also evaluated. RESULTS: All radiologic measurements exhibited excellent inter- and intra-observer reliabilities. The reliabilities between Post_HcRV and both I_HRV and Pre_HRV, as well as between pre- and postoperative ITS orientations, showed excellent agreement (intraclass correlation coefficients: 0.953, 0.952, and 0.873, respectively). The humeral component was inserted within 5° in 86.8% of the planned humeral RV cases. CONCLUSIONS: The HcRV measured using the BGR and ITS orientations achieved good accuracy for restoring the planned humeral RV using a retroversion guide with the forearm axis. Therefore, this new radiological measurement method can aid orthopedic surgeons in confirming Post_HcRV on CT scans without an elbow.
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BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
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Péptidos beta-Amiloides , Tomografía de Emisión de Positrones , Hormonas Tiroideas , Proteínas tau , Humanos , Masculino , Femenino , Anciano , Proteínas tau/sangre , Proteínas tau/metabolismo , Estudios Transversales , Hormonas Tiroideas/sangre , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/sangre , Persona de Mediana Edad , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Tiroxina/sangre , Tirotropina/sangre , Estudios de CohortesRESUMEN
PURPOSE: Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research. MATERIALS AND METHODS: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests. RESULTS: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD. CONCLUSION: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.
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Enfermedad de Alzheimer , Atrofia , Encéfalo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Proteínas tau , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Edad de Inicio , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Aminopiridinas , Amiloide/metabolismo , Compuestos de Anilina , Atrofia/patología , Benzotiazoles , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Pruebas Neuropsicológicas , Quinolinas , Proteínas tau/metabolismoRESUMEN
This study aimed to evaluate the antioxidant and anti-inflammatory activities of Lonicera caerulea L. ethanol extract (LCEE) and water extract (LCWE) in vitro. We primarily evaluated the improvement effect of LCWE and LCEE on hydrogen peroxide (H2O2)-induced oxidative damage and lipopolysaccharide (LPS)-induced inflammatory damage in RAW 264.7 cells by detecting oxidation-related indicators and inflammatory factors, respectively. Cellular studies showed that LCWE and LCEE increased superoxide dismutase and catalase antioxidant enzyme levels and decreased malondialdehyde and nitric oxide peroxide levels in H2O2-induced RAW 264.7 cells. Moreover, LCWE and LCEE decreased the secretion of inflammatory factors [e.g., interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α] in LPS-induced RAW 264.7 cells. In conclusion, LCWE and LCEE demonstrated excellent antioxidant and anti-inflammatory effects in vitro. However, LCWE was superior to LCEE, which may be related to its chemical composition and requires further research.
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The image quality received for clinical evaluation is often suboptimal. The goal is to develop an image quality analysis tool to assess patient- and primary care physician-derived images using deep learning model. Dataset included patient- and primary care physician-derived images from August 21, 2018 to June 30, 2022 with 4 unique quality labels. VGG16 model was fine tuned with input data, and optimal threshold was determined by Youden's index. Ordinal labels were transformed to binary labels using a majority vote because model distinguishes between 2 categories (good vs bad). At a threshold of 0.587, area under the curve for the test set was 0.885 (95% confidence interval = 0.838-0.933); sensitivity, specificity, positive predictive value, and negative predictive value were 0.829, 0.784, 0.906, and 0.645, respectively. Independent validation of 300 additional images (from patients and primary care physicians) demonstrated area under the curve of 0.864 (95% confidence interval = 0.818-0.909) and area under the curve of 0.902 (95% confidence interval = 0.85-0.95), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 300 images were 0.827, 0.800, 0.959, and 0.450, respectively. We demonstrate a practical approach improving the image quality for clinical workflow. Although users may have to capture additional images, this is offset by the improved workload and efficiency for clinical teams.
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OBJECTIVES: The aims of the study were (i) to examine the changes in echocardiographic parameters and (ii) to compare the fate of myocardial segments with akinesia and without akinesia on preoperative echocardiography after coronary artery bypass grafting. METHODS: One hundred one patients who underwent complete revascularization, who were assessed by preoperative, before discharge, postoperative 3- and 12-month echocardiographic examinations, and who showed all patent grafts at postoperative 1-year angiograms were included. Echocardiographic left ventricular ejection fraction was assessed, and a 16-segment model was adopted for regional analysis of the left ventricle. A total of 1616 segments were analysed based on a 6-point scale: 1 = normal (N = 1083), 2 = mild hypokinesia (N = 2), 3 = moderate hypokinesia (N = 74), 4 = severe hypokinesia (N = 150), 5 = akinesia without thinning (N = 259) and 6 = akinesia with thinning (N = 48). RESULTS: The serial left ventricular ejection fraction measured preoperatively, before discharge, at postoperative 3- and 12-months were 0.48 ± 0.14, 0.49 ± 0.12, 0.49 ± 0.10 and 0.54 ± 0.10, respectively. The left ventricular ejection fraction significantly increased over time during the postoperative 12 months (P < 0.001). Wall motion scores tended to decrease over time in both segment groups with akinesia and without akinesia (P < 0.001), and improvement of the wall motion was significantly higher in the segment group with akinesia than in the segment group without akinesia (P < 0.001). CONCLUSIONS: The left ventricular ejection fraction and regional wall motion improved over time during the postoperative 12 months, regardless of the presence of an akinetic segment. Complete revascularization including akinetic myocardium should be considered when performing coronary artery bypass grafting.
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BACKGROUND AND OBJECTIVE: Our aim was to develop an artificial intelligence (AI) system for detection of urolithiasis in computed tomography (CT) images using advanced deep learning capable of real-time calculation of stone parameters such as volume and density, which are essential for treatment decisions. The performance of the system was compared to that of urologists in emergency room (ER) scenarios. METHODS: Axial CT images for patients who underwent stone surgery between August 2022 and July 2023 comprised the data set, which was divided into 70% for training, 10% for internal validation, and 20% for testing. Two urologists and an AI specialist annotated stones using Labelimg for ground-truth data. The YOLOv4 architecture was used for training, with acceleration via an RTX 4900 graphics processing unit (GPU). External validation was performed using CT images for 100 patients with suspected urolithiasis. KEY FINDINGS AND LIMITATIONS: The AI system was trained on 39 433 CT images, of which 9.1% were positive. The system achieved accuracy of 95%, peaking with a 1:2 positive-to-negative sample ratio. In a validation set of 5736 images (482 positive), accuracy remained at 95%. Misses (2.6%) were mainly irregular stones. False positives (3.4%) were often due to artifacts or calcifications. External validation using 100 CT images from the ER revealed accuracy of 94%; cases that were missed were mostly ureterovesical junction stones, which were not included in the training set. The AI system surpassed human specialists in speed, analyzing 150 CT images in 13 s, versus 38.6 s for evaluation by urologists and 23 h for formal reading. The AI system calculated stone volume in 0.2 s, versus 77 s for calculation by urologists. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our AI system, which uses advanced deep learning, assists in diagnosing urolithiasis with 94% accuracy in real clinical settings and has potential for rapid diagnosis using standard consumer-grade GPUs. PATIENT SUMMARY: We developed a new AI (artificial intelligence) system that can quickly and accurately detect kidney stones in CT (computed tomography) scans. Testing showed that this system is highly effective, with accuracy of 94% for real cases in the emergency department. It is much faster than traditional methods and provides rapid and reliable results to help doctors in making better treatment decisions for their patients.
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OBJECTIVE: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer. METHODS: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed. RESULTS: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating ß-3 tubulin expression to suppress microtubule dynamics. CONCLUSION: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.
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Bencimidazoles , Resistencia a Antineoplásicos , Neoplasias Ováricas , Paclitaxel , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Bencimidazoles/farmacología , Paclitaxel/farmacología , Línea Celular Tumoral , Animales , Ratones , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Apoptosis/efectos de los fármacos , Ratones Desnudos , Proliferación Celular/efectos de los fármacosRESUMEN
This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.
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Recent research has emphasized the role of macrophage-secreted factors on skeletal muscle metabolism. We studied Sargassum Serratifolium ethanol extract (ESS) in countering lipopolysaccharide (LPS)-induced changes in the macrophage transcriptome and their impact on skeletal muscle. Macrophage-conditioned medium (MCM) from LPS-treated macrophages (LPS-MCM) and ESS-treated macrophages (ESS-MCM) affected C2C12 myotube cells. LPS-MCM upregulated muscle atrophy genes and reduced glucose uptake, while ESS-MCM reversed these effects. RNA sequencing revealed changes in the immune system and cytokine transport pathways in ESS-treated macrophages. Protein analysis in ESS-MCM showed reduced levels of key muscle atrophy-related proteins, TNF-α, IL-6, IL-1, and GDF-15. These proteins play crucial roles in muscle function. These findings highlight the intricate relationship between the macrophage transcriptome and their secreted factors in either impairing or enhancing skeletal muscle function. ESS treatment has the potential to reduce macrophage-derived cytokines, preserving skeletal muscle function.
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Macrófagos , Atrofia Muscular , Extractos Vegetales , Sargassum , Sargassum/química , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/patología , Transcriptoma , Lipopolisacáridos , Citocinas/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Línea Celular , Medios de Cultivo Condicionados/farmacología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacosRESUMEN
Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.