GDF-15 alleviates diabetic nephropathy via inhibiting NEDD4L-mediated IKK/NF-κB signalling pathways.

Podocyte inflammatory injury has been indicated to play a pivotal role in the occurrence and development of diabetic nephropathy (DN). However, the pathogenesis of inflammation remains unclear. Recent researches have shown that GDF-15, a member of the transforming growth factor-ß superfamily, were elevated under pathological conditions, such as myocardial ischemia, cancer, as well as inflammation. Here, we demonstrated that GDF-15 could alleviate podocyte inflammatory injury by modulating the NF-κB pathway. GDF-15 and other pro-inflammatory factors, such as TNF-α, IL-1ß, and IL-6 were upregulated in the serum of HFD/STZ rat models. GDF-15 was also elevated in diabetic glomeruli and hyperglycemic stimuli treated-podocytes. The silence of GDF-15 in HG-stimulated podocytes further augmented inflammation and podocyte injury, while overexpression of GDF-15 significantly reduced the inflammatory response in podocytes. Mechanistically, we demonstrated that GDF-15 could inhibit the nuclear translocation of NF-κB through IKK and IκBα by interaction with ubiquitin ligase NEDD4L. Taken together, our data suggested a protective mechanism of elevated GDF-15 in DN through obstruction of ubiquitin degradation of IKK by inhibiting NEDD4L expression, thus decreasing the activation of NF-κB and relieving the inflammation. GDF-15 could serve as a potential therapeutic target for DN.

Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Microfluidic origami nano-aptasensor for peanut allergen Ara h1 detection.

In this study, an origami microfluidic electrochemical nano-aptasensor was developed for the rapid detection of the peanut allergen Ara h1. Specifically, the microfluidic aptasensor was fabricated through sequential folding of a piece of chromatography paper substrate patterned with microchannel and screen-printed electrodes. Aptamer-decorated black phosphorus nanosheets (BPNSs) were electrodeposited onto the paper-based electrode surface as sensing probes for enhanced electrochemical detection and high specificity and selectivity. Critical design parameters (the concentration of probe, time for self-assembly of aptamer and reaction time) were investigated to optimize the aptasensor performance. The prepared aptasensor was able to complete detection within 20 min and demonstrated a linear range from 50 ~ 1000 ng/mL with a detection limit of 21.6 ng/mL. The aptasensor was successfully used to detect the Ara h1 spiked cookie dough sample. The proposed method reduces the gap between complex lab testing and food allergen analysis at the point of need.

Microfluidic thread-based electrochemical aptasensor for rapid detection of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is one of the foodborne bacteria that widely present in seafood as well as the leading cause of seafood-associated bacterial gastroenteritis. Traditional identification of such pathogens mainly relies on culturing methods, ELISA or PCR. These methods are usually laborious, time-consuming with poor diagnosis competences, or require costly and bulky equipment though of high sensitivity. In this study, a thread-based microfluidic electrochemical aptasensor was designed, fabricated and tested by using label-free aptamer immunosensing technology for rapid and highly sensitive detection of Vibrio parahaemolyticus in seafood. Both the microfluidic channels and electrodes were simply fabricated on threads. Molybdenum disulfide (MoS2) nanosheets were used to obtain enhanced sensitivity of the electrochemical measurement. When used in detecting Vibrio parahaemolyticus, the proposed aptasensor has a dynamic detection range of 10-106 CFU mL-1 with a detection limit of 5.74 CFU mL-1. Compared with traditional plate counting method, the proposed aptasensor has higher detection sensitivity and less assay time (30 min), while high specificity and accuracy are kept. The proposed microfluidic thread-based electrochemical aptasensor grabs the potential to detect other pathogens by simply functionalizing the threaded electrodes with aptamers for targeted biological substances.