Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary ...exosomes of KTRs.
Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).
Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
Fermented extracts have evolved to be a potential alternative to synthetic chemicals, owing to their anti-inflammatory and anti-bacterial properties. This study intends to assess the potential of ...fermented Zanthoxylum schinifolium extract for use in biomedical applications. Probiotic bacteria, Lactobacillus rhamnosus A6-5, were deployed as a seed culture for fermentation. The fermented extract showed greater tyrosinase inhibitory activity and reduced melanin production (58.3%) compared with the raw extract. Cytotoxicity assay inferred that 500 μg/mL is the ideal non-toxic concentration with maximum cell viability. In addition, DAPI staining did not show any damage to the chromatin structure of the cells. The anti-aging property of the fermented extract was confirmed by a decrease in IL-6 content. The fermented extract showed lower MIC (40 mg/mL) and MBC (60 mg/mL), indicating greater anti-bacterial activity than the raw extract. The results confirmed that the fermented Z. schinifolium extract has high biomedical properties compared with the raw extract and can be used as an ideal skin whitening agent.
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•16S rDNA of the isolated strain exhibited 98% identity with Lactobacillus rhamnosus strain LE38.•Radical scavenging activity of the fermented Zanthoxylum schinifolium extract was higher than raw extract.•Cytotoxicity beyond 500 μg/mL of the fermented extract was lower than raw extract.•Bioactivity of Z. schinifolium fermented extract was increased compared to raw extract.•Presence of new metabolites in the fermented extract was confirmed by LC MS/MS.
Bacterial cancer therapy relies on the fact that several bacterial species are capable of targeting tumor tissue and that bacteria can be genetically engineered to selectively deliver therapeutic ...proteins of interest to the targeted tumors. However, the challenge of bacterial cancer therapy is the release of the therapeutic proteins from the bacteria and entry of the proteins into tumor cells. This study employed an attenuated Salmonella typhimurium to selectively deliver the mitochondrial targeting domain of Noxa (MTD) as a potential therapeutic cargo protein, and examined its anti-cancer effect. To release MTD from the bacteria, a novel bacterial lysis system of phage origin was deployed. To facilitate the entry of MTD into the tumor cells, the MTD was fused to DS4.3, a novel cell-penetrating peptide (CPP) derived from a voltage-gated potassium channel (Kv2.1). The gene encoding DS4.3-MTD and the phage lysis genes were placed under the control of PBAD , a promoter activated by L-arabinose. We demonstrated that DS4.3-MTD chimeric molecules expressed by the Salmonellae were anti-tumoral in cultured tumor cells and in mice with CT26 colon carcinoma.
Postharvest blueberry softening was investigated by observing microstructural changes of blueberry in spectrum and texture using hyperspectral microscope imaging and deep learning technology. More ...specifically, textural features were examined from grey-level co-occurrence matrix (GLCM) computed from hypercube of blueberry cells. GLCMs predetermined with nine different pixel distances and four orientations were extracted from three input image sources (i.e., single-band images of 530 nm, 680 nm, and double-band images pairing of these two bands). The optimum GLCM features were mean, variance, homogeneity, contrast, dissimilarity, entropy, energy, and correlation. With these GLCM features, the parenchyma cell textures were visually and statistically characterized over different firmness. To confirm the effectiveness of textural features, Fusion-Nets combining 1D-CNN for spectra and ResNet50 for GLCMs were trained and evaluated with four different distances (i.e., 16, 32, 64, 128 in pixels) and three image sources. According to the results of textural feature analysis, contrast, entropy, variance, dissimilarity, homogeneity, and energy were different (p < 0.05) over two firmness categories (1.96–3.92 N and 3.92–9.81 N in shear force) for average GLCMs with 16–64 pixel distance calculated from a single-band image source (i.e., 530 nm or 680 nm band images). A Fusion-Net with spectra of cell walls and GLCMs with 64-pixel distance from 680 nm band images distinguished the firmness categories with 95% classification accuracy and 90% Matthew's correlation coefficient (MCC), which outperformed the previous Fusion-Net with spectra and band images, which were 85% test accuracy with 73% test MCC. While implying a close relationship between blueberry softening and textural change in hyperspectral images of blueberry microstructures, these results provide a basis for further research on development of non-destructive methods to measure blueberry firmness with macroscopic imaging platforms.
•Texture of blueberry cells was different between soft and firm blueberries.•Textural variation among blueberries was considerable.•Firmness classification was achieved using spectra and texture with deep learning.•HMI provided knowledge for development of an imaging method to distinguish firmness.
This study aimed to examine the anti-diabetic effect of germinated waxy black rice (GWBR) using streptozotocin (STZ)-induced diabetic rats. In the diabetic rats, GWBR supplementation for 8 weeks ...reduced plasma blood glucose concentrations, improved glucose clearance and prevented diabetes-induced weight loss. Rats with STZ-induced diabetes who received GWBR supplementation exhibited decreased expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter (GLUT) 2 genes and proteins in the small intestine via decreases in hepatocyte nuclear factor (HNF)-1α, HNF-1β, and HNF-4α, transcriptional factors that are involved in the regulation of SGLT1 and GLUT2, compared with the rats with STZ-induced diabetes that did not receive GWBR supplements. GWBR supplementation also enhanced the expression of GLUT4 and the genes and proteins involved in GLUT4 translocation, such as insulin receptor (IR) and insulin receptor substrate 1 (IRS1), and increased the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB, Akt) proteins in skeletal muscle. GWBR further increased glycogen synthase (GS) 1 by decreasing glycogen synthase kinase (GSK)-3β in skeletal muscle. Interestingly, GWBR recovered STZ-impaired pancreatic β-cells, resulting in increased insulin synthesis and secretion. In addition, GWBR reduced serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, aspartate transferase and alanine transferase concentrations and increased high-density lipoprotein cholesterol concentrations. Taken together, these findings suggest that GWBR could be a candidate for improving the diabetic condition by regulating glucose uptake in the intestine and muscle and regulating the secretion of insulin from the pancreas.
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•An overview of recent applications of metabolomics in seaweed research is provided.•Primary and functional secondary metabolite in seaweed is discussed.•The metabolite content in ...seaweed is affected by the prevailing environmental conditions.•The effects of global warming on seaweed metabolite profile changes are discussed.
Seaweed, an important food resource in several Asian countries, contains various metabolites, including sugars, organic acids, and amino acids; however, their content is affected by prevailing environmental conditions. This review discusses seaweed metabolomics, especially the distribution of primary and functional secondary metabolites (e.g., carotenoids, polyphenols) in seaweed. Additionally, the effects of global warming on seaweed metabolite profile changes are discussed. For example, high temperatures can increase amino acid levels in seaweeds. Overall, understanding the effects of global warming on seaweed metabolite profiles can be useful for evaluating the nutritional composition of seaweeds as food. This review provides an overview of recent applications of metabolomics in seaweed research as well as a perspective on the nutrient content and cultivation of seaweeds under climate change scenarios.
Electrospinning techniques enable the production of continuous fibers with dimensions on the scale of nanometers from a wide range of natural and synthetic polymers. The number of recent studies ...regarding electrospun polysaccharides and their derivatives, which are potentially useful for regenerative medicine, is increasing dramatically. However, difficulties regarding the processibility of the polysaccharides (e.g., poor solubility and high surface tension) have limited their application. In this review, we summarize the characteristics of various polysaccharides such as alginate, cellulose, chitin, chitosan, hyaluronic acid, starch, dextran, and heparin, which are either currently being used or have potential to be used for electrospinning. The recent progress of nanofiber matrices electrospun from polysaccharides and their biomedical applications in tissue engineering, wound dressings, drug delivery, and enzyme immobilization are discussed.
‘Seolhyang’ strawberry is harvested before it is fully ripened and treated with CO2 to extend the shelf-life. However, the volatile changes in the ‘Seolhyang’ strawberry after short-term CO2 ...treatment have not been investigated, although the volatile profile is an important quality attribute. Herein, we investigated the effect of short-term high CO2 treatment on the changes in the composition of volatile compounds in ‘Seolhyang’ strawberries at two ripening stages (i.e., half-red and bright-red) during cold storage using headspace solid-phase microextraction and gas chromatography-mass spectrometry. Furthermore, the effect of CO2 treatment on fruit quality with respect to the aroma was investigated. A total of 30 volatile compounds were identified. Storage increased the volatile compound concentrations, and the total concentration of volatiles in the CO2-treated strawberries was lower than that of the untreated strawberries during storage. The production of some characteristic strawberry volatiles (e.g., 4-methoxy-2,5-dimethyl-3(2H)-furanone) was inhibited in CO2-treated strawberries. However, CO2 treatment helped maintain the concentrations of hexanal and 2-hexenal, which are responsible for the fresh odor in strawberries. Interestingly, CO2 treatment suppressed the production of off-odor volatiles, acetaldehyde, and hexanoic acid during strawberry storage. Thus, short-term CO2 treatment may help maintain the fresh aroma of strawberries during cold storage.
Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers ...in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (
= 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (
= 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.
Various factors can affect renal and patient outcome in idiopathic membranous nephropathy (iMN). We aimed to identify predictors of renal and patient survival in patients with iMN, with a special ...focus on outcomes among older patients.
We retrieved data on 1,776 patients (mean age 53.0 ± 14.7 years; 1,075 60.5% males) diagnosed with iMN from the Korean GlomeruloNEphritis sTudy (KoGNET), a database compiled from 18 centers in Korea.
The cohort included 428 (24.1%) patients over 65 years old. Compared to younger patients, this group had lower hemoglobin and serum albumin levels, a higher incidence of nephrotic-range proteinuria, and higher prevalences of hypertension and diabetes. At last follow-up, complete or partial remission rates were not significantly different between the older and younger groups. Older age (HR: 0.98, 95%CI: 0.97-0.99), elevated hemoglobin (HR: 0.82, 95%CI: 0.72-0.93), high serum albumin (HR: 0.66, 95%CI: 0.44-0.99), and a high estimated glomerular filtration rate (HR: 0.96, 95%CI: 0.95-0.97) at biopsy were good predictors of renal outcomes. Significant risk factors for patient survival were older age (HR: 1.04, 95%CI: 1.01-1.10) and hypertension at biopsy (HR: 2.76, 95%CI: 1.30-5.90).
Older patients with iMN had favorable renal outcomes, but poor patient survival, compared to younger patients. Prognostic information on outcomes in this study might be helpful for optimizing the management of patients with iMN.
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