Galectin-12 modulates Kupffer cell polarization to alter the progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is caused by an imbalance in lipid metabolism and immune response to pose a risk factor for liver fibrosis. Recent evidence indicates that M2 macrophages secrete transforming growth factor-ß1, which contributes to liver fibrosis. Galectin-12 has been demonstrated to regulate lipid metabolism and macrophage polarization. The purpose of this study is to investigate the role of galectin-12 in the development of nonalcoholic fatty liver disease and fibrosis. Liver tissue from wild-type C57BL/6 mice fed with a high-fat diet containing cholesterol and cholic acid for 4-12 weeks was used to examine galectin-12 expression and its correlation with nonalcoholic fatty liver disease. Furthermore, the effects of galectin-12 on M2 macrophages during the progression of nonalcoholic fatty liver disease were investigated by studying Kupffer cells from galectin-12 knockout mice and doxycycline-inducible Gal12-/-THP-1 cells. Ablation of galectin-12 promoted M2 polarization of Kupffer cells, as indicated by higher levels of M2 markers, such as arginase I and chitinase 3-like protein 3. Furthermore, the activation of signal transducer and activator of transcription 6 was significantly higher in Gal12-/- macrophages activated by interleukin-4, which was correlated with higher levels of transforming growth factor-ß1. Moreover, Gal12-/- macrophage-conditioned medium promoted hepatic stellate cells myofibroblast differentiation, which was indicated by higher α-smooth muscle actin expression levels compared with those treated with LacZ control medium. Finally, we demonstrated that galectin-12 knockdown negatively regulated the suppressor of cytokine signaling 3 levels. These findings suggested that galectin-12 balances M1/M2 polarization of Kupffer cells to prevent nonalcoholic fatty liver disease progression.

Development of a rapid aptamer-chemiluminescence sensor for detecting glyphosate pesticide residue in soybeans.

Glyphosate (GLY) is a widely used herbicide worldwide, particularly in cultivating genetically modified soybeans resistant to GLY. However, routine multi-residue analysis does not include GLY due to the complexity of soybean matrix components that can interfere with the analysis. This study presented the development of an aptamer-based chemiluminescence (Apt-CL) sensor for rapidly screening GLY pesticide residue in soybeans. The GLY-binding aptamer (GBA) was developed to bind to GLY specifically, and the remaining unbound aptamers were adsorbed onto gold nanoparticles (AuNPs). The signal was in the form of luminol-H2O2 emission, catalyzed by the aggregation of AuNPs in a chemiluminescent reaction arising from the GLY-GBA complex. The outcomes demonstrated a robust linear relationship between the CL intensity of GLY-GBA and the GLY concentration. In the specificity test of the GBA, only GLY and Profenofos were distinguished among the fifteen tested pesticides. Furthermore, the Apt-CL sensor was conducted to determine GLY residue in organic soybeans immersed in GLY as a real sample, and an optimal linear concentration range for detection after extraction was found to be between 0.001 and 10 mg/L. The Apt-CL sensor exploits the feasibility of real-time pesticide screening in food safety.

Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression.

Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL/6 mice administered a high-fat/high-cholesterol/high-cholic acid diet (HFCCD) and BPA (50 mg/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (α-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression.

Application of a Novel Biosensor for Salivary Conductivity in Detecting Chronic Kidney Disease.

The prevalence of chronic kidney disease (CKD) is increasing, and it brings an enormous healthcare burden. The traditional measurement of kidney function needs invasive blood tests, which hinders the early detection and causes low awareness of CKD. We recently designed a device with miniaturized coplanar biosensing probes for measuring salivary conductivity at an extremely low volume (50 µL). Our preliminary data discovered that the salivary conductivity was significantly higher in the CKD patients. This cross-sectional study aims to validate the relationship between salivary conductivity and kidney function, represented by the estimated glomerular filtration rate (eGFR). We enrolled 214 adult participants with a mean age of 63.96 ± 13.53 years, of whom 33.2% were male. The prevalence rate of CKD, defined as eGFR < 60 mL/min/1.73 m2, is 11.2% in our study. By multivariate linear regression analyses, we found that salivary conductivity was positively related to age and fasting glucose but negatively associated with eGFR. We further divided subjects into low, medium, and high groups according to the tertials of salivary conductivity levels. There was a significant trend for an increment of CKD patients from low to high salivary conductivity groups (4.2% vs. 12.5% vs. 16.9%, p for trend: 0.016). The receiver operating characteristic (ROC) curves disclosed an excellent performance by using salivary conductivity combined with age, gender, and body weight to diagnose CKD (AUC equal to 0.8). The adjusted odds ratio of CKD is 2.66 (95% CI, 1.10−6.46) in subjects with high salivary conductivity levels. Overall, salivary conductivity can serve as a good surrogate marker of kidney function; this real-time, non-invasive, and easy-to-use portable biosensing device may be a reliable tool for screening CKD.

Computer-aided diagnosis of isocitrate dehydrogenase genotypes in glioblastomas from radiomic patterns.

World Health Organization tumor classifications of the central nervous system differentiate glioblastoma multiforme (GBM) into wild-type (WT) and mutant isocitrate dehydrogenase (IDH) genotypes. This study proposes a noninvasive computer-aided diagnosis to interpret the status of IDH in glioblastomas from transformed magnetic resonance imaging patterns. The collected image database was composed of 32 WT and 7 mutant IDH cases. For each image, a ranklet transformation which changed the original pixel values into relative coefficients was 1st applied to reduce the effects of different scanning parameters and machines on the underlying patterns. Extracting various textural features from the transformed ranklet images and combining them in a logistic regression classifier allowed an IDH prediction. We achieved an accuracy of 90%, a sensitivity of 57%, and a specificity of 97%. Four of the selected textural features in the classifier (homogeneity, difference entropy, information measure of correlation, and inverse difference normalized) were significant (P < .05), and the other 2 were close to being significant (P = .06). The proposed computer-aided diagnosis system based on radiomic textural features from ranklet-transformed images using relative rankings of pixel values as intensity-invariant coefficients is a promising noninvasive solution to provide recommendations about the IDH status in GBM across different healthcare institutions.

A Portable System to Monitor Saliva Conductivity for Dehydration Diagnosis and Kidney Healthcare.

Chronic kidney disease (CKD) has become a major issue in long-term healthcare. It is caused by recurrent kidney injury, which is possible induced by dehydration and heat stress. Therefore, it is important to access the dehydration diagnosis on fields. Conventional instruments for assessing dehydration from blood and urine samples are expensive and time-consuming. These disadvantages limit their applications in high-risk groups susceptible to kidney disease. To address this unmet need, this study presents a portable miniaturized device for dehydration diagnosis with clinical saliva samples. With co-plane coating-free gold electrodes, the dehydration diagnosis was achieved with a saliva specimen at low volumes (50-500 µL). To examine the characteristics, the developed device was assessed by using standard conductivity solutions and the examined variation was <5%. To validate the use for field applications, saliva samples were measured by the developed device and the measured results were compared with standard markers of serum osmolality (N = 30). These data indicate that the measured saliva conductivity is consistent with serum osmolality. And it shows significant difference between healthy adults and healthy farmers (p < 0.05), who typically suffer high risks of CKD. Based on this work, the proposed device and measurement offer a useful method to diagnosis dehydrations and indicate possible potential for CKD.