Targeting IL-11R/EZH2 signaling axis as a therapeutic strategy for osteosarcoma lung metastases.

Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression of genes repressed by histone methyltransferase EZH2, including members of the WNT pathway, a known target pathway of EZH2. Exogenous IL-11 increased the global levels of histone H3 lysine 27 trimethylation, evidence of EZH2 activation. Treatment with the EZH2 inhibitor GSK126 significantly reduced in vitro proliferation and increased cell-cycle arrest and apoptosis, which were partially mediated through the WNT pathway. In vivo, treatment of an orthotopic nude mouse model of OS with GSK126 inhibited lung metastatic growth and prolonged survival. In addition, significantly shorter recurrence-free survival was seen in OS patients with high levels of EZH2 in their primary tumors (P < .05). This suggests that IL-11Rα promotes OS lung metastasis via activation of EZH2. Thus, blocking EZH2 activity may be an effective strategy for inhibiting OS lung metastasis and improving prognosis.

Serum Lipoprotein(a) Levels as a Predictor of Aortic Stiffness in Patients on Long-Term Peritoneal Dialysis.

BACKGROUND Lipoprotein (a) [Lp(a)] is associated with atherosclerosis and cardiovascular mortality in patients with kidney failure. Aortic stiffness (AS), measured primarily by carotid-femoral pulse wave velocity (cfPWV), reflects vascular aging and precedes end-organ failure. This study aimed to evaluate the association between serum Lp(a) levels and cfPWV in patients undergoing peritoneal dialysis (PD). MATERIAL AND METHODS In this cross-sectional study, which included 148 patients with long-term PD for end-stage kidney failure, cfPWV was measured using a cuff-based method. AS was defined as a cfPWV exceeding 10 m/s, and an enzyme-linked immunosorbent assay was used to determine serum Lp(a) levels. Univariate and multivariate regression analyses were performed to identify the clinical correlates of AS. RESULTS There were 32 (21.6%) patients diagnosed with AS. Based on the multivariate logistic regression analysis, the odds ratio for AS was 1.007 (95% confidence interval, 1.003-1.011; P=0.001) for every 1 mg/L increase in Lp(a) levels. Multivariate linear regression analysis showed that Lp(a) (P<0.001), age (P=0.003), waist circumference (P=0.008), systolic blood pressure (P=0.010), and diabetes mellitus (P<0.001) were positively associated with cfPWV. The area under the receiver operating characteristic curve for Lp(a) in differentiating AS from non-AS was 0.770 (95% confidence interval, 0.694-0.835; P<0.0001). CONCLUSIONS Serum Lp(a) level was independently associated with cfPWV and AS in patients with PD.

The Prognostic Role of Serum ß-Trace Protein Levels among Patients on Maintenance Hemodialysis.

Cardiovascular (CV) diseases are the most commonly encountered etiology of mortality in patients having kidney failure. ß-Trace protein (BTP) is a biomarker of glomerular filtration function as well as a potential predictor of adverse CV outcomes. This study aimed to determine the prognostic value of BTP in patients on chronic hemodialysis (HD). A total of 96 patients undergoing HD were enrolled. Baseline variables were collected, and the patients were tracked for 3 years. Twenty-five patients died at 3 years. Those who experienced mortality were noted to have higher serum concentrations of BTP and a higher incidence of diabetes mellitus (DM). The area under the receiver operating characteristic curve for serum BTP distinguishing mortality from survival was 0.659 (95% confidence interval [CI], 0.555-0.752; p = 0.027). After the adjustment of variables potentially affecting survival rates, BTP levels above the median (adjusted hazard ratio [aHR]: 2.913, 95% CI, 1.256-6.754; p = 0.013), the presence of DM (aHR: 2.474, 95% CI, 1.041-5.875; p = 0.040), and low serum albumin (aHR: 0.298, 95% CI, 0.110-0.806; p = 0.017) independently correlated with survival in HD patients. Serum BTP is a novel biomarker for predicting overall outcomes in HD patients.

Nephroprotective effects of coriander (Coriandrum sativum) leaves aqueous extracts in aristolochic acid-intoxicated zebrafish embryos.

Coriander is a notable medicinal plant known for its diverse properties, including anti-inflammatory, antioxidant, anticancer, analgesic, and anti-diabetic effects. Despite its recognized health benefits, research on its nephroprotective properties is limited. This study aimed to investigate the potential nephroprotective properties of an aqueous extract derived from coriander leaves using an aristolochic acid-intoxicated zebrafish model. To assess kidney abnormalities induced by aristolochic acid (AA), we utilized the transgenic line Tg(wt1b:egfp), which expresses green fluorescent protein (GFP) in the kidney. Our previous report indicated that AA exposure leads to acute renal failure in zebrafish characterized by kidney malformation and impaired renal function. However, pretreatment of coriander extract (CE) can mitigate kidney malformations induced by AA. In addition, CE pretreatment reduces the accumulation of red blood cells in the glomerular region. To verify the nephroprotective effects of CE, we analyzed renal function by measuring the glomerular filtration rate in zebrafish embryos. Results indicate that CE partially mitigates renal function impairment caused by AA exposure, suggesting its potential to attenuate AA-induced renal failure. Mechanistically, pretreatment with CE reduces the expression of proinflammatory and proapoptotic genes induced by AA. This suggests that CE likely alleviates acute renal failure by reducing inflammation and apoptosis. As a result, we regard zebrafish as a valuable model for screening natural compounds that have the potential to alleviate AA-induced nephrotoxicity.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (ß: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; ß: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Ellagic acid ameliorates renal fibrogenesis by blocking epithelial-to-mesenchymal transition.

Objectives: Ellagic acid (EA), a kind of polyphenol found in numerous fruits and vegetables, has anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-fibrotic effects against a variety of diseases, but its role in mediating renal fibrogenesis remains unknown. Materials and Methods: We used an in vivo mouse unilateral ureteral obstruction (UUO) model and an in vitro model with HK-2 cell lines treated with EA and transforming growth factor ß1 (TGF-ß1). The expression of epithelial-to-mesenchymal transition (EMT)-related proteins of UUO mice was examined using immunohistochemical staining. Liver function and renal function were evaluated using biochemical testing. Western blot analysis was used to determine the proteins related to EMT, and MTT assay was used to determine cell viability. Results: In UUO mice fed EA, both microscopical examination with immunohistochemical staining and western blotting protein analysis showed reduced expression of fibrotic (α-SMA, fibronectin, and collagen I)- and EMT (vimentin and N-cadherin)-related proteins, compared with sham control. In HK-2 cells treated with TGF-ß1, EA decreased motility as well as expression of α-SMA, collagen-I, fibronectin, N-cadherin, and vimentin. Conclusion: EA reduced the progression of the morphological transformations and concomitantly suppressed the expression of fibrotic- and EMT-related proteins in vitro and in vivo. These findings improved our understanding of the role of EA in suppressing renal fibrogenesis and demonstrated the promising role EA may play in the management of chronic kidney disease.

Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

Corosolic acid inhibits metastatic response of human renal cell carcinoma cells by modulating ERK/MMP2 signaling.

Corosolic acid (CA), a plant-derived pentacyclic triterpenoid, has potent anti-inflammatory, anti-metabolic, and anti-neoplastic actions against a variety of human cancers. However, the specific mechanism by which CA inhibits the progression of renal cell carcinoma (RCC) is yet unclear. We found that CA (≤8 µM) had no influence on either the growth or viability of RCC cell lines (786-O, ACHN, and Caki-1) or normal HK2 cells. However, in a dose-dependent manner, CA prevented the invasion and migration of RCC cells. Human protease array analysis showed that CA reduced MMP2 expression. At increasing concentrations of CA, the expression of MMP2 was dose-dependently reduced, as shown by western blot and RT-PCR analyses as well as immunofluorescence staining. CA also stimulated ERK1/2 phosphorylation in 786-O and Caki-1 cells. Transfection of CA-treated RCC cells with siRNA-ERK restored MMP2 protein expression and the motility and invasion capabilities of RCC cells. Molecular docking study results showed that CA and MMP2 interact strongly. These findings elucidate the mechanism by which CA prevents RCC cells from migrating and invading, and these findings indicate that CA may be a potential anti-metastatic therapy for RCC.

Endocan as a Potential Marker for Predicting All-Cause Mortality in Hemodialysis Patients.

Endocan, a pro-inflammatory cytokine and pro-angiogenic factor, is a marker of endothelial dysfunction and has been proven to correlate with cardiovascular disease. In hemodialysis (HD) patients, cardiovascular disease is the major cause of mortality. Our study aimed to investigate the relationship between serum endocan and all causes of mortality in HD patients. A total of 103 patients, aged over 20 years old and undergoing HD for more than 3 months, were included and followed for 36 months. Mortality events, serum endocan, biochemical data, body mass index, systolic and diastolic blood pressure, baseline characteristics, and the use of antihypertensive and lipid-lowering drugs were recorded. In our study, a total of 26 deaths (25.2%) occurred. Hemodialysis patients with diabetes mellitus, older age, higher serum endocan, and lower creatinine and albumin levels had a higher risk of mortality. Adjusting for prognostic variables, HD patients with higher serum endocan (p = 0.010) and lower serum creatinine (p = 0.034) demonstrated significantly higher all-cause mortality. In our study, increased endocan and lower creatinine are associated with all-cause mortality in HD patients. Serum endocan levels could serve as a biomarker for a high mortality risk in HD patients.

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus.

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (ß = 0.52, 95% confidence interval [CI] = 0.01-1.03, p = 0.046), high HOMA-IR (ß = 0.60, 95% CI = 0.12-1.08, p = 0.015), and a high PD glucose load (ß = 0.58, 95% CI = 0.08-1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

Production of Porous Biochar from Cow Dung Using Microwave Process.

To valorize livestock manure, the present study investigated the production of biochar from cow dung (CD) by microwave pyrolysis. The pore properties and chemical characteristics of CD and CD-based biochar products were found to correlate with the process parameters like microwave power (300-1000 W) and residence time (5-20 min). The findings indicated that CD is an excellent biomass based on the richness of lignocellulosic constituents from the results of proximate analysis and thermogravimetric analysis (TGA). Higher calorific values were obtained at mild microwave conditions, giving the maximal enhancement factor 139% in comparison with the calorific value of CD (18.97 MJ/kg). Also, it can be concluded that the biochar product obtained at 800 W for a holding time of 5 min had the maximal BET surface area of 127 m2/g and total pore volume of 0.104 cm3/g, which were microporous and mesoporous in the nitrogen adsorption-desorption adsorption analysis. On the other hand, the CD-based biochar contained oxygen-containing functional groups and inorganic minerals based on the spectroscopic analyses by Fourier-transform infrared spectroscopy (FTIR) and energy-dispersive X-ray spectroscopy (EDS), thus featuring to be prone to hydrophilicity in aqueous solutions.

Effects of the Supercritical Fluid Extract of Magnolia figo on Inducing the Apoptosis of Human Non-Small-Cell Lung Cancer Cells.

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography-mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment.

Urinary Klotho Excretion: A Key Regulator of Sodium Homeostasis in Chronic Kidney Disease Stage 2-4.

BACKGROUND Soluble alpha-klotho (klotho) is considered an important regulator of mineral homeostasis in patients with chronic kidney disease (CKD). Since the mineral transport proteins are located on the apical membrane of renal tubular cells, we hypothesized that urine klotho may also be involved in their homeostasis. We aimed to investigate the associations between serum and urine klotho and their impacts on mineral homeostasis in patients with stage 2 to 4 CKD. MATERIAL AND METHODS Serum, spot urine, and 24-h urine of klotho were measured by using enzyme-linked immunosorbent assay. Fractional excretion of sodium, potassium, calcium, phosphate, magnesium, and klotho were calculated. RESULTS A total of 53 patients with CKD stages 2 to 4 were enrolled in this cross-sectional study. The mean age was 71.1±10.5 years, and 68% were men. Linear regression analysis showed that serum log-transformed klotho was negatively associated with log-transformed fractional excretion of klotho (log-FEKlotho) (ß=-0.085, P=0.02), showing that urinary klotho excretion could negatively regulate serum klotho levels. Moreover, our multivariate stepwise regression showed log-fractional excretion of sodium was positively associated with log-FEKlotho (ß=0.138, P=0.032). This implied urinary klotho excretion positively regulated urinary sodium excretion. CONCLUSIONS Our study showed that urine klotho excretion resulted in decreased serum klotho levels and enhanced urinary sodium excretion in patients with CKD stages 2 to 4. In addition to serum klotho, we found, for the first time, that urine klotho also played a significant role in sodium homeostasis.

Alpha-mangostin alleviate renal interstitial fibrosis via suppression of TGF-ß1/Smad/ERK signaling axis in vitro and in vivo.

α-mangostin (α-MG), a natural derivative of coumarin, exhibits anti-inflammatory, antioxidant and anti-fibrotic effects. This study aimed to determine the effect of α-MG treatment in mediating the process of renal interstitial fibrosis. We found that α-MG could alleviate tubule-interstitial damage and decrease fibrotic (α-smooth muscle actin [α-SMA], fibronectin, and collagen I), and epithelial-mesenchymal transition (EMT) protein (N-cadherin, Snail, Slug, TGF-ß1 and vimentin) expression in unilateral ureteral obstruction (UUO) mice with chronic kidney disease. α-MG significantly decreased motility as well as inhibited expression of fibrotic- and EMT-related proteins in TGF-ß1-induced HK2 cells. To clarify the molecular mechanisms of α-MG in reducing renal interstitial fibrosis, we used a MEK inhibitor (U0126) or Smad inhibitor (SB431542) cotreatment with α-MG. This is the first study is to demonstrate the antifibrotic effects of α-MG by targeting the TGF-ß1/ERK/Smad-mediated EMT signaling pathway, is even more effective against renal interstitial fibrosis.

MicroRNA regulators of vascular pathophysiology in chronic kidney disease.

Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.

Serum Osteoprotegerin Levels and the Vascular Reactivity Index in Patients with Hypertension.

Background and Objectives: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the mediator in the process of vascular endothelial dysfunction. Impaired endothelial function has an intimate link with hypertension (HTN) and is associated with significant morbidity and mortality. This study was to investigate the connection between OPG and endothelial dysfunction in patients having HTN. Materials and Methods: There are 102 patients with HTN included. For the purpose of determining the levels of OPG, a commercial enzyme-linked immunosorbent test kit was applied. The vascular reactivity index (VRI), which is assessed via the digital thermal monitoring, provides information on endothelial function. Results: Ten patients with HTN (9.8%) were classified as having poor vascular reactivity (VRI < 1.0), 46 HTN patients (45.1%) as having intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 46 HTN patients (45.1%) were classified as having high vascular reactivity (VRI ≥ 2.0). A greater serum OPG level (p < 0.001) and older age (p = 0.022) were linked to impaired vascular reactivity. The estimated glomerular filtration rate (r = 0.196, p = 0.048) was positively correlated with VRI values in hypertensive participants, while advanced age (r = -0.222, p = 0.025) and the log-transformed OPG level (log-OPG, r = -0.357, p < 0.001) were negatively correlated with VRI. Serum log-OPG level was shown to be strongly and independently correlated with VRI values in HTN individuals after multivariable forward stepwise linear regression analysis (ß = -0.357, adjusted R2 change = 0.119, p < 0.001). Conclusions: In patients with HTN, serum OPG levels were adversely correlated with VRI and probably had a role in endothelial dysfunction.

Serum Trimethylamine N-Oxide Level Is Positively Associated with Aortic Stiffness Measured by Carotid-Femoral Pulse Wave Velocity in Patients Undergoing Maintenance Hemodialysis.

Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association between serum TMAO levels and carotid-femoral pulse wave velocity (cfPWV) in patients receiving hemodialysis (HD) therapy. In total, 115 patients with HD were enrolled in this study. The AS group included patients whose cfPWV was >10 m/s. Using high-performance liquid chromatography and mass spectrometry, the levels of serum TMAO were measured. The AS group included 42 (36.5%) patients, and compared with the non-AS group, the rates of diabetes, hypertension, older age, systolic blood pressure, serum glucose, and TMAO levels were high. In the multivariate logistic regression analysis, serum TMAO and age were independently linked with AS after correcting for the factors significantly associated with AS. Following multivariate stepwise linear regression analysis, serum TMAO in these individuals was found to be strongly correlated with cfPWV values (p < 0.001). In patients on chronic HD, serum TMAO level is an independent measure of AS and strongly correlated with cfPWV.

An approach to the diagnosis of lumbar disc herniation using deep learning models.

Background: In magnetic resonance imaging (MRI), lumbar disc herniation (LDH) detection is challenging due to the various shapes, sizes, angles, and regions associated with bulges, protrusions, extrusions, and sequestrations. Lumbar abnormalities in MRI can be detected automatically by using deep learning methods. As deep learning models gain recognition, they may assist in diagnosing LDH with MRI images and provide initial interpretation in clinical settings. YOU ONLY LOOK ONCE (YOLO) model series are often used to train deep learning algorithms for real-time biomedical image detection and prediction. This study aims to confirm which YOLO models (YOLOv5, YOLOv6, and YOLOv7) perform well in detecting LDH in different regions of the lumbar intervertebral disc. Materials and methods: The methodology involves several steps, including converting DICOM images to JPEG, reviewing and selecting MRI slices for labeling and augmentation using ROBOFLOW, and constructing YOLOv5x, YOLOv6, and YOLOv7 models based on the dataset. The training dataset was combined with the radiologist's labeling and annotation, and then the deep learning models were trained using the training/validation dataset. Results: Our result showed that the 550-dataset with augmentation (AUG) or without augmentation (non-AUG) in YOLOv5x generates satisfactory training performance in LDH detection. The AUG dataset overall performance provides slightly higher accuracy than the non-AUG. YOLOv5x showed the highest performance with 89.30% mAP compared to YOLOv6, and YOLOv7. Also, YOLOv5x in non-AUG dataset showed the balance LDH region detections in L2-L3, L3-L4, L4-L5, and L5-S1 with above 90%. And this illustrates the competitiveness of using non-AUG dataset to detect LDH. Conclusion: Using YOLOv5x and the 550 augmented dataset, LDH can be detected with promising both in non-AUG and AUG dataset. By utilizing the most appropriate YOLO model, clinicians have a greater chance of diagnosing LDH early and preventing adverse effects for their patients.

Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

Background and aim: In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. Experimental procedure: The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Results and conclusion: Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 µL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

Investigation of the Relationship between Body Parameters and mAs Using Non-Contact Two-Dimensional Thickness Measurement in Chest Digital Radiography.

The current study aimed to investigate the relationship between body parameters and the current-time product (mAs) in chest digital radiography using a non-contact infrared thickness-measurement sensor. An anthropomorphic chest phantom was first used to understand variations in mAs over multiple positionings during chest radiography when using the automatic exposure control (AEC) technique. In a human study, 929 consecutive male subjects who underwent regular chest examinations were enrolled, and their height (H), weight (W), and body mass index (BMI) were recorded. In addition, their chest thickness (T) was measured at exhalation using a non-contact infrared sensor, and chest radiography was then performed using the AEC technique. Finally, the relationship between four body parameters (T, BMI, T*BMI, and W/H) and mAs was investigated by fitting the body parameters to mAs using three curve models. The phantom study showed that the maximum mAs was 1.76 times higher than the lowest mAs during multiple positionings in chest radiography. In the human study, all chest radiographs passed the routine quality control procedure and had an exposure index between 100 and 212. In curve fitting, the comparisons showed that W/H had a closer relationship with mAs than the other body parameters, while the first-order power model with W/H fitted to mAs performed the best and had an R-square of 0.9971. We concluded that the relationship between W/H and mAs in the first-order power model may be helpful in predicting the optimal mAs and reducing the radiation dose for chest radiography when using the AEC technique.