Association of Malnutrition with Risk of Acute Kidney Injury: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) is a complex clinical syndrome of hospitalization that may be affected by undernutrition and metabolic changes. The aim of this meta-analysis was to systematically assess the association between malnutrition and the risk of prevalent AKI. Materials and Methods: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, and Chinese databases (WANFANG, VIP, and CKI) from database inception until May 1, 2023, for studies evaluating the association of malnutrition with the risk of AKI. Summary odds ratios (ORs) were estimated using a random-effects model. Results: We identified 17 observational studies, which included 273,315 individuals. Compared with patients with normal nutritional status, those with malnutrition had a 125% increased risk of prevalent AKI (pooled ORs, 2.25; 95% confidence interval, 1.80-2.82). Malnutrition was also significantly associated with prevalent AKI across all subgroups when subgroup analyses were performed on covariates such as region, study design, age, sample size, malnutrition assessment method, patient characteristics, covariate adjustment degree, and risk of bias. Meta-regression models demonstrated no significant differences in AKI risk between patients with malnutrition and without malnutrition. Conclusions: Our results suggest that malnutrition may be a potential target for AKI prevention. However, well-designed studies with ethnically or geographically diverse populations are needed to evaluate strategies and interventions to prevent or slow the development and progression of AKI in malnourished individuals.

Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS. METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545. FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed. INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment. FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A novel porous granular scaffold for the promotion of trabecular bone repair by time-dependent alteration of morphology.

Granular scaffolds have been extensively used in the clinic to repair irregular maxillofacial defects. There remain some challenges for the repair of trabecular structures in cancellous bone due to the reticular lamella-like morphology. In this study, we fabricated a novel granular scaffold by rational design of components with different degradation rates so that the morphology of the novel scaffold can evolve to match the growth period of bone cells. Here, polycaprolactone (PCL) was used to fabricate porous microspheres as a skeleton with slow degradation. The macropores were filled with quick degraded gelatin to form complete microspheres. Asynchronous degradation of the two components altered the morphology of the evolutive scaffold from compact to porous, gradually exposing the ridge-like skeletons. This scaffold reversed the decline of cellular adhesion to simple porous skeletons during the initial adhesion. Furthermore, the cells were able to grow into the pores and adhere onto the skeletons with an elongated cellular morphology, facilitating osteogenic differentiation. This novel scaffold was experimentally proven to promote the regeneration of alveolar bone along with a good percentage of bone volume and the formation of trabecular structures. We believe this morphology-evolved scaffold is highly promising for regenerative applications in the clinic.

Engeletin Attenuates Aß1-42-Induced Oxidative Stress and Neuroinflammation by Keap1/Nrf2 Pathway.

Alzheimer's disease (AD) is a serious neuropathologic disease characterized by aggregation of amyloid-ß (Aß) peptide. Aß-mediated oxidative stress and neuroinflammation play crucial role in the development of AD. Engeletin is a flavononol glycoside that possesses anti-inflammatory effect. However, the effects of engeletin on AD have not been investigated. In the present study, we investigated the role of engeletin in AD using an in vitro AD model. Murine microglia BV-2 cells were stimulated with Aß1-42 (5 µM) for 24 h to induce oxidative stress and inflammation. Our results showed that treatment with engeletin suppressed Aß1-42-induced viability reduction and lactate dehydrogenase (LDH) release in BV-2 cells. Engeletin attenuated Aß1-42-induced oxidative stress in BV-2 cells, as proved by decreased production of reactive oxygen species (ROS) and malonaldehyde (MDA) and increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Aß1-42-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were inhibited by engeletin treatment. Besides, engeletin inhibited Aß1-42-induced production and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Engeletin enhanced Aß1-42-induced activation of Kelch-like ECH-associated protein 1 (Keap1)/nuclear transcription factor E2-related factor 2 (Nrf2) signaling pathway in BV-2 cells. Inhibition of Keap1/Nrf2 signaling pathway reversed the inhibitory effects of engeletin on Aß1-42-induced oxidative stress and inflammation in BV-2 cells. Taken together, engeletin attenuated Aß1-42-induced oxidative stress and inflammation in BV-2 cells via regulating the of Keap1/Nrf2 pathway. These findings indicated that engeletin might be served as a therapeutic agent for the treatment of AD.

Effect of nanoscale bioactive glass with radial spherical particles on osteogenic differentiation of rat bone marrow mesenchymal stem cells.

To validate the feasibility of two types of bioactive glass that contains spherical and radical spherical nano-sized particles in promoting bone repair, we hypothesize that radical spherical nano-sized particles have higher bone repair effectiveness than spherical one due to the physicochemical properties. We rigorously compared the physicochemical properties and bioactivities of these two types of bioactive glass. Specifically, we measured the size, surface morphology, concentration of ionic-dissolution products, bioactivity, and biological effects of two groups of bioactive glass on rat bone marrow mesenchymal stem cells (rBMSCs) and evaluate their effect on proliferation and osteogenic differentiation of rBMSCs in vitro. We observed that spherical nano-bioactive glass (SNBG) was spherical with smooth boundary, while the radial spherical nano-bioactive glass (RSNBG) had radial pore on the surface of particle boundary. When the two materials were immersed in simulated body fluid for 24 h, RSNBG produced more and denser hydroxyapatite carbonate than SNBG. The concentration of Ca and Si ions in RSNBG 24 h extract is higher than that of SNBG, while the concentration of P ions is lower. Proliferation, alkaline phosphatase (ALP) activity, intracellular Ca ion concentrations defined as the number of mineralized nodules produced, and the expression of osteogenic genes were significantly higher in rBMSCs co-cultured with 50 µg/mL RSNBG than SNBG. Overall, these results validated our hypothesis that RSNBG can provide better benefit than SNBG for inducing proliferation and osteogenic differentiation in rBMSCs, in turn suggested the feasibility of this RSNBG in further studies and utilization toward the ends of improved bone repair effectiveness.

Effects of miR-26a on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by a Mesoporous Silica Nanoparticle - PEI - Peptide System.

INTRODUCTION: RNA-based therapy for bone repair and regeneration is a highly safe and effective approach, which has been extensively investigated in recent years. However, the molecular stability of RNA agents still remains insufficient for clinical application. High porosity, tunable size, and ideal biodegradability and biosafety are a few of the characters of mesoporous silicon nanoparticles (MSNs) that render them a promising biomaterial carrier for RNA treatment. MATERIALS AND METHODS: In this study, a novel miR-26a delivery system was constructed based on MSNs. Next, we assessed the miRNA protection of the delivery vehicles. Then, rat bone marrow mesenchymal stem cells (rBMSCs) were incubated with the vectors, and the transfection efficiency, cellular uptake, and effects on cell viability and osteogenic differentiation were evaluated. RESULTS: The results demonstrated that the vectors protected miR-26a from degradation in vitro and delivered it into the cytoplasm. A relatively low concentration of the delivery systems significantly increased osteogenic differentiation of rBMSCs. CONCLUSION: The vectors constructed in our study provide new methods and strategies for the delivery of microRNAs in bone tissue engineering.