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OBJECTIVES: To explore the value of high-resolution MR vessel wall imaging (HR-VWI) based plaque characteristics combined with cardiovascular health (CVH) metrics in the risk evaluation of ischemic stroke attributed to middle cerebral artery (MCA) atherosclerotic stenosis. METHODS: Retrospective analysis of 209 participants with middle cerebral atherosclerosis, 146 patients with high signal in the MCA area on DWI were included in the symptomatic group, and 63 patients were included in the asymptomatic group. The degree of stenosis, enhancement ratio, plaque burden, remodeling index, and intraplaque hemorrhage were measured and compared between groups. Seven CVH metrics and other clinical data were obtained. The association between these factors and ischemic stroke was investigated by univariate and multivariate analysis. RESULTS: The degree of stenosis [OR, 1.036 (95 % CI, 1.014-1.058); P = 0.001], plaque burden [OR, 0.958 (95 % CI, 0.928-0.989); P = 0.009], intraplaque hemorrhage [OR, 3.530 (95 % CI, 1.233-10.110); P = 0.019], physical activity [OR, 4.321 (95 % CI, 1.526-12.231); P = 0.006], and diet [OR, 8.986 (95 % CI, 2.747-29.401); P < 0.001] were the independent characteristics associated with the occurrence of ischemic stroke. ROC curve showed that the combination of plaque characteristics, diet, and physical activity achieved the highest AUC of 0.828 (95 % CI 0.770-0.877; P < 0.001), with sensitivity and specificity being 86.30 % and 66.67 %, respectively. CONCLUSION: Plaque characteristics combined with CVH metrics may identify high-risk populations for ischemic stroke and offer novel insights into risk evaluation and stratification.
Subject(s)
Ischemic Stroke , Humans , Male , Female , Ischemic Stroke/diagnostic imaging , Middle Aged , Retrospective Studies , Aged , Magnetic Resonance Angiography/methods , Plaque, Atherosclerotic/diagnostic imaging , Intracranial Arteriosclerosis/diagnostic imaging , Intracranial Arteriosclerosis/complicationsABSTRACT
OBJECTIVES: To explore the value of middle cerebral artery (MCA) plaque characteristics in predicting the outcomes of subacute ischemic stroke and the incremental value of the previous diet on predictive performance. METHODS: One hundred and thirty-seven subacute ischemic stroke patients attributed to MCA plaques were included and analyzed in this prospective study. The National Institute of Health Stroke Scale (NIHSS) score, Mediterranean Diet Adherence Screener (MEDAS) score, and other clinical data were assessed. The plaque area, degree of stenosis, plaque burden, enhancement ratio, remodeling type, and intraplaque hemorrhage were measured using high-resolution MR vessel wall imaging (HR-VWI). Multivariable logistic regression analysis and receiver operating characteristic curve analysis were performed to assess the predictive performance of clinical and plaque characteristics for subacute ischemic stroke outcomes at 3 months. RESULTS: Patients with poor outcomes exhibited high NIHSS scores, and low MEDAS scores (P<0.001). Plaque burden, enhancement ratio, and degree of stenosis were significantly higher in patients with poor outcomes (P<0.001). Multivariate analyses further indicated that NIHSS score (P=0.001), MEDAS score (P=0.013), and enhancement ratio (P=0.011) were independent predictors of subacute ischemic stroke outcomes. The three models' area under the curve (AUC) values were 0.811, 0.844, and 0.794. Combining these three factors resulted in an AUC of 0.908 (P<0.001). CONCLUSIONS: The combination of NIHSS score, MEDAS score, and enhancement ratio showed significant superiority in the prognostic evaluation of subacute ischemic stroke. Clinical data combined with plaque characteristics improves the accuracy of 3-month outcome prediction on subacute ischemic stroke.
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BACKGROUND: Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. METHODS: This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63-0.96) and 0.77(95%CI:0.60-0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55-0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. CONCLUSION: The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.
Subject(s)
Imaging, Three-Dimensional , Neoplasm Invasiveness , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Male , Female , Middle Aged , Neoplasm Invasiveness/diagnostic imaging , Prospective Studies , Imaging, Three-Dimensional/methods , Aged , Magnetic Resonance Imaging/methods , ROC Curve , Nomograms , RadiomicsABSTRACT
PURPOSE: To investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa). METHODS: Patients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models' performances were quantified by area under the receiver operating characteristic curve (AUC). RESULTS: MR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46-82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31-82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv's 0.805 (p = 0.014), and similar to the combined diffusion model's AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv's 0.694 (p = 0.020), and similar to the combined diffusion model's AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05). CONCLUSION: CTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively. CRITICAL RELEVANCE STATEMENT: Our study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures. KEY POINTS: Muscular invasion largely determines bladder salvageability in bladder cancer patients. Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis. Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa.
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The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.
Subject(s)
Cnidarian Venoms , Metalloproteases , Molecular Docking Simulation , Scyphozoa , Animals , Metalloproteases/chemistry , Metalloproteases/metabolism , Cnidarian Venoms/chemistry , Tetracycline/toxicity , Transcriptome/drug effectsABSTRACT
Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.
Subject(s)
Acetates , Cyclopropanes , NF-kappa B , Psoriasis , Quinolines , Sulfides , Humans , Animals , Mice , Interleukin-17 , Th17 Cells , Psoriasis/drug therapy , Cell Differentiation , CytokinesABSTRACT
Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017-1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.
Subject(s)
Hypersensitivity , Immunoglobulin G , Child , Animals , Humans , Allergens , Immunoglobulin E , Diet , Pyroglyphidae , Dermatophagoides pteronyssinus , MilkABSTRACT
Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality. The prediction of the progression of AKI to long-term injury has been difficult for renal disease treatment. Radiologists are keen for the early detection of transition from AKI to long-term kidney injury, which would help in the preventive measures. The lack of established methods for early detection of long-term kidney injury underscores the pressing needs of advanced imaging technology that reveals microscopic tissue alterations during the progression of AKI. Fueled by recent advances in data acquisition and post-processing methods of magnetic resonance imaging (MRI), multiparametric MRI is showing great potential as a diagnostic tool for many kidney diseases. Multiparametric MRI studies offer a precious opportunity for real-time noninvasive monitoring of pathological development and progression of AKI to long-term injury. It provides insight into renal vasculature and function (arterial spin labeling, intravoxel incoherent motion), tissue oxygenation (blood oxygen level-dependent), tissue injury and fibrosis (diffusion tensor imaging, diffusion kurtosis imaging, T1 and T2 mapping, quantitative susceptibility mapping). The multiparametric MRI approach is highly promising but the longitudinal investigation on the transition of AKI to irreversible long-term impairment is largely ignored. Further optimization and implementation of renal MR methods in clinical practice will enhance our comprehension of not only AKI but chronic kidney diseases. Novel imaging biomarkers for microscopic renal tissue alterations could be discovered and benefit the preventative interventions. This review explores recent MRI applications on acute and long-term kidney injury while addressing lingering challenges, with emphasis on the potential value of the development of multiparametric MRI for renal imaging on clinical systems. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
Subject(s)
Acute Kidney Injury , Diffusion Tensor Imaging , Humans , Kidney/pathology , Magnetic Resonance Imaging/methods , Acute Kidney Injury/pathology , Magnetic Resonance Spectroscopy , Diffusion Magnetic Resonance Imaging/methodsABSTRACT
Calcin is a group ligand with high affinity and specificity for the ryanodine receptors (RyRs). Little is known about the effect of its acidic residues on the spacial structure as well as the interaction with RyRs. We screened the opicalcin1 acidic mutants and investigated the effect of mutation on activity. The results indicated that all acidic mutants maintained the structural features, but their surface charge distribution underwent significant changes. Molecular docking and dynamics simulations were used to analyze the interaction between opicalcin1 mutants and RyRs, which demonstrated that all opicalcin1 mutants effectively bound to the channel domain of RyR1. This stable binding induced a pronounced asymmetry in the structure of the RyR tetramer, exhibiting a high degree of structural dissimilarity. [3H]Ryanodine binding to RyR1 was enhanced in D2A and D15A, which was similar to opicalcin1, but that effect was suppressed in E12A and E29A and reversed for the DE-4A, thereby inhibiting ryanodine binding. Opicalcin1 and DE-4A also exhibited the ability to form stable docking structures with RyR2. Acidic residues play a crucial role in the structure of calcin and its functional interaction with RyRs that is beneficial for the calcin optimization to develop more active peptide lead compounds for RyR-related diseases.
Subject(s)
Calcium Signaling , Ryanodine Receptor Calcium Release Channel , Ryanodine/metabolism , Ryanodine Receptor Calcium Release Channel/chemistry , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism , Molecular Docking Simulation , Mutation , Calcium/metabolismABSTRACT
Baicalin (BAI), the main active component of Scutellaria baicalensis, has significant anti-inflammatory and antibacterial effects. Echinacoside (ECH), an active component from Echinacea purpurea, has significant antiangiogenesis and antioxidant effects. In previous studies, BAI or ECH has been used for some skin inflammation problems by topical treatment. Psoriasis (PSO) is a common inflammatory skin disease with typical features such as excessive inflammatory response and vascular proliferation in skin lesions. Because of the anti-inflammatory effect of BAI and the antiangiogenic activity of ECH, it is proposed that the combination of BAI and ECH can ameliorate psoriatic skin lesions better than a single component. This study aims to explore the effects and potential mechanisms of BAI combined with ECH on imiquimod (IMQ)-induced psoriatic skin lesions by topical treatment. Transcriptome analysis first showed that the TNF signaling pathway and the VEGF signaling pathway were significantly enriched in IMQ-induced psoriatic skin lesions. Topical application of BAI combined with ECH could ameliorate IMQ-induced skin lesions in mice, especially the better effects of B2-E1 (BAI/ECH = 2:1). Network pharmacology analysis and molecular docking indicated that BAI-treated PSO on the skin by regulating the TNF signaling pathway, and ECH treated PSO on the skin by regulating the VEGF signaling pathway. Meanwhile, the ELISA test and the qPCR assay showed that BAI combined with ECH could inhibit the expression of key cytokines and genes related to the TNF signaling pathway and the VEGF signaling pathway. Zebrafish experiments demonstrated the anti-inflammatory and antiangiogenic effects of BAI combined with ECH and revealed the potential mechanisms associated with regulating the inflammation-related TNF signaling pathway and the angiogenesis-related VEGF signaling pathway. This suggested that BAI combined with ECH may be a promising topical agent to ameliorate psoriatic skin lesions in the future.
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Ecological drought monitoring is important for regional status assessment and protection of water resources. In this study, we constructed a new ecological drought index, the kernel temperature vegetation drought index (kTVDI), by using the kernel normalized vegetation index (kNDVI) to improve the temperature vegetation drought index (TVDI) in Inner Mongolia. We further analyzed the spatial and temporal distribution of ecological drought in Inner Mongolia during 2000-2022 and the future trend of ecological drought by using segmented linear regression model, Theil-Sen median, Mann-Kendall test, and Hurst index. The results showed that kTVDI performed better in monitoring ecological drought than TVDI. From 2000 to 2022, kTVDI showed a decreasing trend in the growing season in Inner Mongolia, but the change was not significant, and a sudden change occurred in 2016, and the wetting trend after the sudden change was more obvious. During the study period, ecological drought in 23.6% of the areas of Inner Mongolia showed an aggravating trend, and ecological drought was alleviated in 46.5% of the area. In the future, ecological drought would be exacerbated in the eastern part but alleviated in the central and western parts of Inner Mongolia.
Subject(s)
Climate Change , Droughts , Temperature , Seasons , China , Forecasting , EcosystemABSTRACT
Bacterial meningitis is a serious complication after neurosurgery and has a high mortality rate. Early diagnosis and timely treatment are crucial or will have disastrous consequences. The classic triad of bacterial meningitis lacks sensitivity and specificity. Therefore, the diagnosis of post-neurosurgical bacterial meningitis relies on cerebrospinal fluid. But traditional cerebrospinal fluid parameters are not completely reliable in diagnosing post-neurosurgical bacterial meningitis. Previous studies have found that CSF lactate concentration is related to bacterial meningitis. But, after the craniocerebral operation, the cerebrospinal fluid of most patients is bloody. Whether red blood cells interfere with diagnosing PNBM based on lactate concentration is limited. In the current study, we further analysis on whether red blood cells interfere with diagnosing PNBM based on lactate concentration. This study aimed to investigate the value of cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis. A prospective observational study was performed on 62 patients at Kunshan First People's Hospital's intensive care unit affiliated with Jiangsu University. We found that erythrocytes do not affect cerebrospinal fluid lactate, and elevated lactate concentrations can be used as a marker for postoperative bacterial meningitis.
Subject(s)
Meningitis, Bacterial , Postoperative Complications , Humans , Lactic Acid/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Neurosurgical Procedures/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Sensitivity and Specificity , Prospective StudiesABSTRACT
BACKGROUND: Cellular senescence is the main cause of skin and organ aging and is associated with a wide range of aging-related diseases. OBJECTIVES: To understand which senolytics, senomorphics, and cell-based therapies have been developed to alleviate and even rejuvenate skin aging and reduce cellular senescence. METHODS: Basic literature for the mode of action of senolytics and senomorphics and their clinical perspectives in daily routine are discussed. RESULTS: Various causes lead to mitochondrial dysfunction and the activation of pro-aging signaling pathways, which eventually lead to cellular senescence with degradation of structural proteins of the dermal connective tissue and severe suppression of regenerative stem cell niches of the skin. CONCLUSIONS: Depletion of senescent cells suppress skin aging and enforce rejuvenation of skin and other organs and their function. The removal of senescent cells by cells of the native immune system is severely disturbed during aging. Selected senolytics and senomorphics are approved and are already on the market.
Subject(s)
Skin Aging , Senotherapeutics , Cellular Senescence , Cell- and Tissue-Based TherapyABSTRACT
OBJECTIVE: Ovarian cancer (OC) is a common malignant tumor in females with high recurrence and poor prognosis. Cisplatin is commonly used for OC clinical treatment, but its efficacy is usually challenged by the chemotherapy resistance of cancer cells. MicroRNAs (miRNAs), including miR-30a-5p, were identified to modulate drug resistance in numerous tumors. However, molecular mechanisms of miR-30a-5p in OC chemoresistance need more illumination. METHODS: MiR-30a-5p and Rap1 interacting factor 1 (RIF1) expression in OC tissues and cells were measured by qRT-PCR. The IC50 of cisplatin-resistant and cisplatin-sensitive OC cells was assessed by MTT assays. OC cell proliferation, apoptosis and migration were measured by EdU assays, TUNEL staining, and wound healing assays, respectively. The protein levels of EMT markers and RIF1 in OC cells were examined by western blotting. The binding capacity between miR-30a-5p and RIF1 was validated by luciferase reporter assays. RESULTS: Our study disclosed miR-30a-5p as a remarkably lowly-expressed miRNA in OC tissues in comparison to matched noncancerous tissues. Compared to parental cell lines, miR-30a-5p was also greatly downregulated in cisplatin-resistant OC cell lines. Additionally, functional assays indicated that miR-30a-5p suppressed malignant behaviors and cisplatin resistance of OC cells. Further, miR-30a-5p was revealed to target and negatively regulate RIF1 expression in OC. Moreover, it was validated that overexpressing RIF1 reverses the inhibitory influence of miR-30a-5p overexpression on malignant behaviors and cisplatin resistance of OC cells. CONCLUSION: MiR-30a-5p reduced cisplatin resistance in OC through downregulation of RIF1, which may be meaningful for targeting drug-resistant tumors.
Subject(s)
Cisplatin , MicroRNAs , Ovarian Neoplasms , Telomere-Binding Proteins , Female , Humans , Apoptosis/genetics , Cisplatin/pharmacology , Fibrinogen , MicroRNAs/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Drug Resistance, NeoplasmABSTRACT
This study mapped the fate of antibiotics in a swine farm with integrated waste treatment including anoxic stabilization, fixed-film anaerobic digestion, anoxic-oxic (A/O), and composting. Results show the prevalent and consistent occurrence of 12 antibiotics in swine waste. Mass balance of these antibiotics was calculated to track their flow and evaluate their removal by different treatment units. The integrated treatment train could effectively reduce antibiotic loading to the environment by 90% (measured as combined mass of all antibiotic residues). Within the treatment train, anoxic stabilization as the initial treatment step, accounted for the highest contribution (43%) to overall antibiotic elimination. Results also show that aerobic was more effective than anaerobic regarding antibiotic degradation. Composting accounted for an additional of 31% removal of antibiotics while anaerobic digestion contributed to 15%. After treatment, antibiotic residues in the treated effluent and composted materials were 2 and 8% of the initial antibiotic loading in raw swine waste, respectively. Ecological risk assessment showed negligible or low risk quotient associated with most individual antibiotics released into the aquatic environment or soil from swine farming. Nevertheless, antibiotic residues in treated water and composted materials together showed significant ecological risk to water and soil organisms. Thus, further work to improve treatment performance or develop new technologies is necessary to reduce the impact of antibiotics from swine farming.
Subject(s)
Anti-Bacterial Agents , Composting , Animals , Swine , Agriculture , Farms , SoilABSTRACT
INTRODUCTION: Metabolic syndrome (MS) has a high prevalence in hemodialysis patients. High asprosin levels are associated with the accumulation of adiposity and an increase in body weight, which may drive the development of this syndrome. The relationship between asprosin and MS in patients on hemodialysis has not been investigated. MATERIALS AND METHODS: We enrolled hemodialysis patients at the hemodialysis center of one hospital in May 2021. MS was defined by the International Diabetes Federation. Fasting serum asprosin levels were measured. ROC curve, multivariate logistic regression and Spearman's rank correlation analyses were performed. RESULTS: In total, 134 patients were included, with 51 with MS and 83 without MS. Among the patients with MS, there was a significantly higher proportion of women (54.9%), prevalence of DM (p < 0.001), waist circumference (p < 0.001), BMI (p < 0.001), triglycerides (p < 0.001), and low-density lipoprotein cholesterol(p < 0.050), and PTH (p < 0.050) contents and a lower diastolic pressure(p < 0.050) and high-density lipoprotein cholesterol level (p < 0.001) than those in patients without MS. The patients with MS exhibited significantly higher serum asprosin levels than the non-MS patients [502.2 ± 153.3 ng/ml vs. 371.5 ± 144.9 ng/ml, p < 0.001]. The AUC for the serum asprosin level was 0.725 (95% confidence interval: 0.639, 0.811). Multivariate logistic regression analysis revealed that asprosin was independently and significantly positively associated with MS (OR = 1.008, p < 0.010). Asprosin levels tended to rise as the number of diagnostic criteria of MS increased (p for trend <0.001). CONCLUSIONS: Fasting serum asprosin is positively correlated with MS and could be an independent risk factor for MS in hemodialysis patients.
Subject(s)
Metabolic Syndrome , Humans , Female , Metabolic Syndrome/epidemiology , Cross-Sectional Studies , Obesity , Cholesterol, LDL , Renal DialysisABSTRACT
This study tracked the fate of nine detected heavy metals in an industrial swine farm with integrated waste treatment, including anoxic stabilization, fixed-film anaerobic digestion, anoxic-oxic (A/O), and composting. Results show that heavy metals exhibited different transformation behaviors in the treatment streamline with Fe, Zn, Cu and Mn as the most abundant ones in raw swine waste. The overall removal of water-soluble heavy metals averaged at 30 %, 24 % and 42 % by anoxic stabilization, anaerobic digestion and A/O unit, respectively. In particular, anoxic stabilization could effectively remove Cu, Mn and Ni; while A/O unit was highly effective for Fe, Cr and Zn elimination from water-soluble states. As such, the environmental risk of liquid products for agricultural irrigation decreased gradually to the safe pollution level in swine waste treatment. Furthermore, heavy metals in the solid (slurry) phase of these bioprocesses could be immobilized with the passivation rate in the range of 42-70 %. Nevertheless, heavy metals preferably transformed from liquid to biosolids to remain their environmental risks when biosolids were used as organic fertilizer in agriculture, thereby requiring effective strategies to advance their passivation in all bioprocesses, particularly composting as the last treatment unit.
Subject(s)
Metals, Heavy , Animals , Swine , Biosolids , Metals, Heavy/analysis , Environmental Pollution , Agricultural Irrigation , Environmental Monitoring/methodsABSTRACT
Background: Triple-negative breast cancer (TNBC) is one of the most prominent neoplasm disorders and lacks efficacious treatments yet. Luteolin (3',4',5,7-tetrahydroxyflavone), a natural flavonoid commonly presented in plants, has been reported to delay the progression of TNBC. However, the precise mechanism is still elusive. We aimed to elucidate the inhibition and molecular regulation mechanism of luteolin on TNBC. Methods: The effects of luteolin on the biological functions of TNBC cells were first evaluated using the corresponding assays for cell counting kit-8 assay, flow cytometry, wound-healing assay, and transwell migration assay, respectively. The mechanism of luteolin on TNBC cells was then analyzed by RNA sequencing and verified by RT-qPCR, Western blot, transmission electron microscopy, etc. Finally, in vivo mouse tumor models were constructed to further confirm the effects of luteolin on TNBC. Results: Luteolin dramatically suppressed cell proliferation, invasion, and migration while favoring cell apoptosis in a dose- and time-dependent manner. In TNBC cells treated with luteolin, SGK1 and AKT3 were significantly downregulated while their downstream gene BNIP3 was upregulated. According to the results of 3D modeling, the direct binding of luteolin to SGK1 was superior to that of AKT3. The inhibition of SGK1 promoted FOXO3a translocation into the nucleus and led to the transcription of BNIP3 both in vitro and in vivo, eventually facilitating the interaction between BNIP3 and apoptosis and autophagy protein. Furthermore, the upregulation of SGK1, induced by luteolin, attenuated the apoptosis and autophagy of the TNBC. Conclusion: Luteolin inhibits TNBC by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling.
ABSTRACT
Currently, there are several treatments approaches available for lung cancer; however, patients who develop drug resistance or have poor survival rates urgently require new therapeutic strategies for lung cancer. In autophagy, damaged proteins or organelles are enclosed within autophagic vesicles with a bilayer membrane structure and transported to the lysosomes for degradation and recirculation. Autophagy is a crucial pathway involved in the clearance of reactive oxygen species (ROS) and damaged mitochondria. Meanwhile, inhibiting autophagy is a promising strategy for cancer treatment. In this study, we found for the first time that Cinchonine (Cin) can act as an autophagy suppressor and exert anti-tumor effects. Cin significantly inhibited the proliferation, migration, and invasion of cancer cells in vitro and the tumor growth and metastasis in vivo, without obvious toxic effects. We found that Cin suppressed the autophagic process by blocking autophagosome degradation through the inhibition of the maturation of lysosomal hydrolases. Cin-mediated autophagy inhibition resulted in the elevated ROS level and the accumulation of damaged mitochondria, which in turn promoted apoptosis. N-acetylcysteine, a potential ROS scavenger, significantly suppressed Cin-induced apoptosis. Additionally, Cin upregulated programmed death-ligand 1 (PD-L1) expression in lung cancer cells by inhibiting autophagy. Compared with monotherapy and control group, the combined administration of anti-PD-L1 antibody and Cin significantly reduced tumor growth. These results suggest that Cin exerts anti-tumor effects by inhibiting autophagy, and that the combination of Cin and PD-L1 blockade has synergistic anti-tumor effects. The data demonstrates the significant clinical potential of Cin in lung cancer treatment.
Subject(s)
Autophagy , Lung Neoplasms , Humans , Reactive Oxygen Species/metabolism , Lung Neoplasms/pathology , Apoptosis , Lysosomes/metabolism , Immunotherapy , Cell Line, TumorABSTRACT
The role of N7-methylguanosine(m7G)-related miRNAs in lung adenocarcinoma (LUAD) remains unclear. We used LUAD data from The Cancer Genome Atlas (TCGA) to establish a risk model based on the m7G-related miRNAs, and divided patients into high-risk or low-risk subgroups. A nomogram for predicting overall survival (OS) was then constructed based on the independent risk factors. In addition, we performed a functional enrichment analysis and defined the oxidative stress-related genes, immune landscape as well as a drug response profile in the high-risk and low-risk subgroups. This study incorporated 28 m7G-related miRNAs into the risk model. The data showed a significant difference in the OS between the high-risk and low-risk subgroups. The receiver operating characteristic curve (ROC) predicted that the area under the curve (AUC) of one-year, three-year and five-year OS was 0.781, 0.804 and 0.853, respectively. The C-index of the prognostic nomogram for predicting OS was 0.739. We then analyzed the oxidative stress-related genes and immune landscape in the high-risk and low-risk subgroups. The data demonstrated significant differences in the expression of albumin (ALB), estimated score, immune score, stromal score, immune cell infiltration and functions between the high-risk and low-risk subgroups. In addition, the drug response analysis showed that low-risk subgroups may be more sensitive to tyrosine kinase inhibitor (TKI) and histone deacetylase (HDAC) inhibitors. We successfully developed a novel risk model based on m7G-related miRNAs in this study. The model can predict clinical prognosis and guide therapeutic regimens in patients with LUAD. Our data also provided new insights into the molecular mechanisms of m7G in LUAD.