Mesenchymal Stem Cell-Derived Exosomes Improved Cerebral Infarction via Transferring miR-23a-3p to Activate Microglia.

Mesenchymal stem cells-derived exosome (MSCs-exo) is a potential method for cerebral infarction (CI) treatment. Here, western blot and qRT-PCR were carried out to measure the expression of proteins and genes, respectively. Modified neurological severity score and TTC staining were used to evaluate the brain injury of middle cerebral artery occlusion (MCAO) rats. Immunohistochemistry was performed to detect the expression of Iba-1, iNOS, and Arg-1 in tissues. Moreover, the rate of M1/M2 microglia was ensured by flow cytometry, and the concentration of pro-inflammatory factors in medium was measured using ELISA. Here, we found that miR-23a-3p is increased in human umbilical cord blood MSCs-exo. Bone marrow MSCs-exo (BMSCs-exo) could improve the injury in neuronal function and reduce the infarct size in vivo. However, the improvement of BMSCs-exo to CI was reversed by miR-23a-3p knockdown. The inhibition of BMSCs-exo to MCAO-induced microglia activation and M1 polarization and the upregulation of pro-inflammatory factors were limited by miR-23a-3p knockdown, which also confirmed in lipopolysaccharide-induced microglia. Overall, our data indicated that MSCs-exo improves CI via transferring miR-23a-3p, thus to induce the deactivation of microglia and M2 polarization. Our study revealed a new regulatory mechanism of CI.

Mussel byssus cuticle-inspired ultrastiff and stretchable triple-crosslinked hydrogels.

Applications in the harsh environment require hydrogels with ultra-stiffness, toughness, and stretchability. However, it remains a challenge to increase the elastic modulus without sacrificing the maximum elongation of hydrogels, because of the trade-off between stiffness and extensibility. Inspired by the crosslinking hierarchy of mussel byssus cuticle, here, we report a strategy to fabricate an ultra-stiff, tough and stretchable triple-crosslinked (TC) hydrogel. The polymer is crosslinked by chemical crosslinker at first, subsequently by introducing a polyphenolic compound, tannic acid (TA), and metal ions. The hydrogen-bond-based network between the polymer and TA works as an extensible and energy-dissipative network, mimicking the matrix of the cuticle, while the higher crosslinked domains formed by the coordinate bonds between TA and metal ions contribute to the stiffness. The triple-crosslinked hydrogel exhibits two orders of magnitude increase in stiffness (E = 58 MPa), but without sacrificing the maximum elongation (ε = 850%), compared with those of metal-free hydrogels (E = 0.18 MPa, and ε = 860%). The combination of ultra-stiffness, toughness, and stretchability in hydrogels is successfully achieved through leveraging the hierarchically cross-linked network based on hydrogen bonding and coordination bonding. Moreover, utilizing the wide distribution of bonding strength of coordination interaction, the mechanical properties of triple-crosslinked hydrogels can be manipulated by using different kinds of catechol-metal coordination.

Stereotactic Aspiration of Necrotic Brain Tissue for Treating Malignant Middle Cerebral Artery Infarction: A Report of 13 Consecutive Cases.

BACKGROUND: This study aimed to evaluate the efficacy and safety of stereotactic aspiration of necrotic brain tissue for treating malignant middle cerebral artery infarction (MMI) in patients older than 60 years of age. CASE DESCRIPTION: A total of 13 consecutive patients with MMI (mean age, 67 ± 6.62 years) were enrolled in the study. These patients were treated with stereotactic aspiration of necrotic brain tissue within 72 hours from stroke onset between January 2016 and June 2017. The surgical results and clinical outcomes were evaluated in response to stereotactic aspiration of necrotic brain tissue. The mean preoperative infarction volume in the patients was found to be 153.46 ± 9.39 mL according to the latest computed tomography scan. The 30-day mortality was 2 out of 13 patients (15.4%). Patients were followed-up for 6 months to evaluate the efficacy of stereotactic aspiration of necrotic brain tissue using the modified Rankin Scale (mRS). Among the 11 surviving surgical patients, 6 (54.5%) had an mRS score of 3 (defined as moderate disability), 4 (36.4%) had an mRS score of 4 (defined as moderate to severe disability), and 1 (9.1%) had an mRS score of 5 (defined as severe disability). The probability of 6-month unfavorable outcome, defined as an mRS score of 5 or 6 (death), was 3 out of 13 (23.1%). CONCLUSIONS: Our results suggest the stereotactic aspiration of necrotic brain tissue is an effective and safe method in patients with MMI who are over 60 years of age.

Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis.

Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12-24h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy.