Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Relationships between preschoolers' attitudes and play behaviors toward classmates with disabilities

This study examined the relationships between 32 typically developing preschoolers??? attitudes and play behaviors toward their classmates with disabilities or developmental delays. Children???s attitudes toward peers with disabilities were assessed using three different methods: child interviews, Sociometric Peer Ratings, and a Social Acceptance Scale. Children???s play behaviors (e.g., solitary, onlooker, parallel play, associative/cooperative play) and teachers??? involvement in children???s play were also observed during free play over a 10-week period. Results show that children???s identification of a classmate with an IEP as having a disability was negatively related to their associaitve/cooperative (AC) play with the classmate. Typically developing children???s sociometric ratings of classmates with disabilities were positively related to their AC play with the classmates with disabilities. In addition, children???s sociometric peer ratings were a stronger indicator of whether a typically developing child would play with a classmate with a disability than was identification of a classmate as having a disability. Suggestions for future research and implications for practices are discussed

Anti-Osteoporotic Activity of Pueraria lobata Fermented with Lactobacillus paracasei JS1 by Regulation of Osteoblast Differentiation and Protection against Bone Loss in Ovariectomized Mice

Osteoporosis is the most common bone disease associated with low bone mineral density. It is the process of bone loss and is most commonly caused by decreased estrogen production in women, particularly after menopause. Pueraria lobata, which contains various metabolites, especially isoflavone, is widely known as regulator for bone mineral contents. In this study, the effects of the P. lobata extract (PE) with or without fermentation with Lactobacillus paracasei JS1 (FPE) on osteoporosis were investigated in vitro and in vivo. The effects of PE and FPE on human osteoblastic MG63 cells, RAW 264.7 cells, and ovariectomized (OVX)-induced model mice were analyzed at various ratios. We found that FPE increased calcium deposition and inhibited bone resorption by in vitro assay. Furthermore, treatment with PE and FPE has significantly restored destroyed trabecular bone in the OVX-induced bone loss mouse model. Overall, FPE demonstrated bioactivity to prevent bone loss by decreasing bone turnover

Optimal temperature for culturing chicken satellite cells to enhance production yield and umami intensity of cultured meat

To investigate the optimal temperature at which to culture chicken muscle satellite cells (MSCs), to improve the production yield and umami intensity of cultured meat, chicken MSCs were cultured at 37, 39, 41, and 43 °C. The most active proliferation and greatest differentiation of MSCs was observed at 41 °C. A significantly shorter doubling time of MSCs and higher area percentage of differentiated myotubes and myofibers were observed at a culture temperature of 41 °C (p < 0.05). Consequently, the total amino acid content and free glutamic acid in cultured muscle tissue (CMT) at 41 °C was significantly higher than at other temperatures (p < 0.05). In addition, the umami and richness intensity of CMT was significantly higher at 41 °C than at other culture temperatures (p < 0.05). Results suggest that chicken MSCs proliferated more actively and differentiated optimally at 41 °C, resulting in a higher amino acid content and umami intensity of CMT

Quality Characteristics of Meat Analogs through the Incorporation of Textured Vegetable Protein: A Systematic Review

Meat analogs produced through extruded products, such as texture vegetable protein (TVP) with the addition of various plant-based ingredients are considered the products that have great potential for replacing real meat. This systematic review was conducted to summarize the evidence of the incorporation of TVP on the quality characteristics of meat analogs. Extensive literature exploration was conducted up to March 2022 for retrieving studies on the current topic in both PubMed and Scopus databases. A total of 28 articles published from 2001 to 2022 were included in the data set based on specific inclusion criteria. It appears that soy protein is by far the most used extender in meat analogs due to its low cost, availability, and several beneficial health aspects. In addition, the studies included in this review were mainly conducted in countries, such as Korea, the USA, and China. Regarding quality characteristics, textural parameters were the most assessed in the studies followed by physicochemical properties, and sensory and taste attributes. Other aspects, such as the development of TVP, the difference in quality characteristics of texturized proteins, and the usage of binding agents in various meat analogs formulations are also highlighted in detail

Theoretical Study on the Effect of Nested Defects for Water Adsorption in Zeolite

Zeolites are useful for CO2 gas separation from post-combustion gases. Also, from previous studies, it has been suggested that the separation performance of CO2 would be affected by water molecules, which always exist in post-combustion gases. Unrealistically, so far, the zeolite structure has been considered as perfect, ignoring the presence of naturally formed defects (i.e. nested silanol defects), which can easily interact with water molecules. Thus, we theoretically investigated both issues by grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulations in this study. To accurately describe the interaction between water and zeolite, we optimized the intermolecular potential energy parameters for reproducing the experimental water adsorption amounts in three kinds of zeolites (i.e. DDR, MFI, and CHA). We found that the number of adsorbed water molecules were found similar regardless of the defect density. Interestingly, it was noticeable that the water molecules were aggregated near the defects from our MD simulation. It implies that the permeability of CO2 can be significantly affected by water around the defective sites