Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.Subject terms: Pharmacology, Molecular biology     

Loss of Ahi1 Impairs Neurotransmitter Release and Causes Depressive Behaviors in Mice

Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1) deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO) mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets.     

Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study

Background aimsPre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders.MethodsAfter providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age.ResultsThe score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation.ConclusionsAutologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function.     

Phrasal Paraphrase Based Question Reformulation for Archived Question Retrieval

Lexical gap in cQA search, resulted by the variability of languages, has been recognized as an important and widespread phenomenon. To address the problem, this paper presents a question reformulation scheme to enhance the question retrieval model by fully exploring the intelligence of paraphrase in phrase-level. It compensates for the existing paraphrasing research in a suitable granularity, which either falls into fine-grained lexical-level or coarse-grained sentence-level. Given a question in natural language, our scheme first detects the involved key-phrases by jointly integrating the corpus-dependent knowledge and question-aware cues. Next, it automatically extracts the paraphrases for each identified key-phrase utilizing multiple online translation engines, and then selects the most relevant reformulations from a large group of question rewrites, which is formed by full permutation and combination of the generated paraphrases. Extensive evaluations on a real world data set demonstrate that our model is able to characterize the complex questions and achieves promising performance as compared to the state-of-the-art methods.     

Profiling and Identification of Small rDNA-Derived RNAs and Their Potential Biological Functions

Small non-coding RNAs constitute a large family of regulatory molecules with diverse functions. Notably, some small non-coding RNAs matched to rDNA have been identified as qiRNAs and small guide RNAs involved in various biological processes. However, a large number of small rDNA-derived RNAs (srRNAs) are usually neglected and yet to be investigated. We systematically investigated srRNAs using small RNA datasets generated by high-throughput sequencing, and found srRNAs are mainly mapped to rRNA coding regions in sense direction. The datasets from immunoprecipitation and high-throughput sequencing demonstrate that srRNAs are co-immunoprecipitated with Argonaute (AGO) proteins. Furthermore, the srRNA expression profile in mouse liver is affected by diabetes. Overexpression or inhibition of srRNAs in cultured cells shows that srRNAs are involved in various signaling pathways. This study presents a global view of srRNAs in total small RNA and AGO protein complex from different species, and demonstrates that srRNAs are correlated with diabetes, and involved in some biological processes. These findings provide new insights into srRNAs and their functions in various physiological and pathological processes.     

(2-Hydroxypropyl)-β-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis

BackgroundPeripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD).ConclusionsTherapeutic angiogenesis by 2HP-β-CD may be beneficial to patients with PAD.