Role of exosomes and exosomal microRNA in muscle-Kidney crosstalk in chronic kidney disease.

Chronic kidney disease (CKD) is a progressive damage of kidneys that can no longer serve the blood-filtering function, and is a life-threatening condition. Skeletal muscle wasting is a common complication of CKD. Yet the relationship between kidney and skeletal muscle in CKD remains unclear. Exosomes, a type of small membrane-bound vesicles released from cells to the extracellular environment, have increasingly received attention due to their potential as mediators of crosstalk between kidneys and different organs, including skeletal muscle. This mini-review summarizes the recent findings that point to the role of exosomes in the cross-talk between kidney and skeletal muscle in CKD. Understanding of the contents and the mechanism of exosome release may prone exosomes be the potential therapeutic targets for CKD.

Anti-epileptic Kunitz-like peptides discovered in the branching coral Acropora digitifera through transcriptomic analysis.

Approximately 50 million people are suffering from epilepsy worldwide. Corals have been used for treating epilepsy in traditional Chinese medicine, but the mechanism of this treatment is unknown. In this study, we analyzed the transcriptome of the branching coral Acropora digitifera and obtained its Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG) and Gene Ontology (GO) annotation. Combined with multiple sequence alignment and phylogenetic analysis, we discovered three polypeptides, we named them AdKuz1, AdKuz2 and AdKuz3, from A. digitifera that showed a close relationship to Kunitz-type peptides. Molecular docking and molecular dynamics simulation indicated that AdKuz1 to 3 could interact with GABAA receptor but AdKuz2-GABAA remained more stable than others. The biological experiments showed that AdKuz1 and AdKuz2 exhibited an anti-inflammatory effect by decreasing the aberrant level of nitric oxide (NO), IL-6, TNF-α and IL-1ß induced by LPS in BV-2 cells. In addition, the pentylenetetrazol (PTZ)-induced epileptic effect on zebrafish was remarkably suppressed by AdKuz1 and AdKuz2. AdKuz2 particularly showed superior anti-epileptic effects compared to the other two peptides. Furthermore, AdKuz2 significantly decreased the expression of c-fos and npas4a, which were up-regulated by PTZ treatment. In addition, AdKuz2 reduced the synthesis of glutamate and enhanced the biosynthesis of gamma-aminobutyric acid (GABA). In conclusion, the results indicated that AdKuz2 may affect the synthesis of glutamate and GABA and enhance the activity of the GABAA receptor to inhibit the symptoms of epilepsy. We believe, AdKuz2 could be a promising anti-epileptic agent and its mechanism of action should be further investigated.

Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification.

Aims/hypothesis: Diabetes mellitus (DM) is associated with comorbid brain disorders. Neuroimaging studies in DM revealed neuronal degeneration in several cortical and subcortical brain regions. Previous studies indicate more pronounced brain alterations in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM). However, a comparison of both types of DM in a single analysis has not been done so far. The aim of this meta-analysis was to conduct an unbiased objective investigation of neuroanatomical differences in DM by combining voxel-based morphometry (VBM) studies of T1DM and T2DM using dual disorder anatomical likelihood estimation (ALE) quantification. Methods: PubMed, Web of Science and Medline were systematically searched for publications until June 15, 2020. VBM studies comparing gray matter volume (GMV) differences between DM patients and controls at the whole-brain level were included. Study coordinates were entered into the ALE meta-analysis to investigate the extent to which T1DM, T2DM, or both conditions contribute to gray matter volume differences compared to controls. Results: Twenty studies (comprising of 1,175 patients matched with 1,013 controls) were included, with seven studies on GMV alterations in T1DM and 13 studies on GMV alterations in T2DM. ALE analysis revealed seven clusters of significantly lower GMV in T1DM and T2DM patients relative to controls across studies. Both DM subtypes showed GMV reductions in the left caudate, right superior temporal lobe, and left cuneus. Conversely, GMV reductions associated exclusively with T2DM (>99% contribution) were found in the left cingulate, right posterior lobe, right caudate and left occipital lobe. Meta-regression revealed no significant influence of study size, disease duration, and HbA1c values. Conclusions/interpretation: Our findings suggest a more pronounced gray matter atrophy in T2DM compared to T1DM. The increased risk of microvascular or macrovascular complications, as well as the disease-specific pathology of T2DM may contribute to observed GMV reductions. Systematic Review Registration: [PROSPERO], identifier [CRD42020142525].

Indentation Stiffness Measurement by an Optical Coherence Tomography-Based Air-Jet Indentation System Can Reflect Type I Collagen Abundance and Organisation in Diabetic Wounds.

There is a lack of quantitative and non-invasive clinical biomechanical assessment tools for diabetic foot ulcers. Our previous study reported that the indentation stiffness measured by an optical coherence tomography-based air-jet indentation system in a non-contact and non-invasive manner may reflect the tensile properties of diabetic wounds. As the tensile properties are known to be contributed by type I collagen, this study was aimed to establish the correlations between the indentation stiffness, and type I collagen abundance and organisation, in order to further justify and characterise the in vivo indentation stiffness measurement in diabetic wounds. In a male streptozotocin-induced diabetic rat model, indentation stiffness, and type I collagen abundance and organisation of excisional wounds were quantified and examined using the optical coherence tomography-based air-jet indentation system and picrosirius red polarised light microscopy, respectively, on post-wounding days 3, 5, 7, 10, 14, and 21. The results showed significant negative correlations between indentation stiffness at the wound centre, and the collagen abundance and organisation. The correlations between the indentation stiffness, as well as collagen abundance and organisation of diabetic wounds suggest that the optical coherence tomography-based air-jet indentation system can potentially be used to quantitatively and non-invasively monitor diabetic wound healing in clinical settings, clinical research or preclinical research.

A comparative investigation of the interaction and pharmacokinetics of hemoglobin with berberine and its oxymetabolite.

Berberine (BBR), isolated from Coptis chinensis, is one type of isoquinoline alkaloids. BBR exerts numerous of bioactivities but the plasma concentration is really low. In our previous study, a new oxymetabolite (OBB) has been discovered and showed superior anti-inflammatory effect comparing with BBR. The aim of this study is to investigate the interaction, metabolite and pharmacokinetics of BBR with hemoglobin. Sprague-Dawley rats were used to carry out the interaction, metabolite and pharmacokinetics of BBR and OBB in vivo. Fluorescence spectra were used to analyse the interaction in vitro. Results showed that OBB could be generated after intravenous injection or incubating with BBR in vitro and in vivo; Both BBR and OBB exerted much stronger binding interaction with hemoglobin than plasma and affect the conformation of bovine hemoglobin and change the fluorescence spectral properties; BBR and OBB were mainly presented and transported in the proteins-bound form. These results provide a new insight to understand the dynamic equilibrium of BBR and OBB within body from the perspective of new metabolic pathways.