MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.

Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue damage. Hence, it is critical to program activated T cells to achieve ROS equilibrium. Here, we determined that miR-23a is indispensable for effector CD4(+) T cell expansion, particularly by providing early protection from excessive necrosis. Mechanistically, miR-23a targeted PPIF, gatekeeper of the mitochondria permeability transition pore, thereby restricting ROS flux and maintaining mitochondrial integrity. Upon acute Listeria monocytogenes infection, deleting miR-23a in T cells resulted in excessive inflammation, massive liver damage, and a marked mortality increase, which highlights the essential role of miR-23a in maintaining immune homeostasis.

Overexpression of synoviolin facilitates the formation of a functional synovial biomembrane.

Digital flexor tendon repair poses a significant challenge for hand surgeons. Currently, extrasynovial tendon grafts are frequently used in clinical settings to bridge flexor tendon defects. However, the healing process is always accompanied by postoperative adhesion. This is mostly due to the fact that no synovial membrane covers the extrasynovial tendon surface, in contrast to the intrasynovial tendon. In this study, we present an efficient method of developing a functional synovial biomembrane on the surface of the extrasynovial tendon. Synoviocytes were isolated from the knee joint of a Japanese white rabbit. After being infected with lentivirus, the over-expression of synoviolin in these synoviocytes was confirmed by semi-quantitative RT-PCR and western blotting. Cellular proliferation and increased hyaluronic acid secretion were confirmed in the synoviolin over-expressing synoviocytes by MTT-based method, cell cycle assays and ELISA. Furthermore, the synoviolin over-expressing synoviocytes were co-cultured with extrasynovial tendons that were harvested from the hind leg of rabbits. After being co-cultured in vitro for 3 and 7 days, these infected synoviocytes were found to accelerate the formation of a biomembrane on the tendon surface compared to the control group. More importantly, Alcian blue staining confirmed the ability of this cultured biomembrane to produce specific matrices containing acidic carboxyl mucopolysaccharides (mainly hyaluronic acid). All these results demonstrate that the over-expression of synoviolin stimulates the proliferation and HA secretion of synoviocytes and facilitates the formation of a functional synovial biomembrane.

Changes of synaptic ultrastructure in the guinea pig interpositus nuclei associate with response magnitude and timing after trace eyeblink conditioning.

Learning-induced changes of synaptic ultrastructure have long been proposed as a mechanism that may contribute to support memory formation. Although recent studies have demonstrated that the interpositus nuclei (IN) play critical role in acquisition and retention of trace conditioned eyeblink responses (CRs), there is now limited evidence associating trace eyeblink conditioning with changes of synaptic ultrastructure in the IN. Here, we investigated this issue using a transmission electron microscope. Adult guinea pigs were randomly allocated to either a trace-paired, delay-paired, unpaired or exposure-only condition. The IN tissue was taken for morphological analysis 1h after the completion of the tenth training session. Serial section analysis of synaptic ultrastructure revealed that trace eyeblink conditioning induced increases in the thickness of excitatory PSD. Classification of the synapses into shape subtypes indicated that the increased thickness of excitatory PSD was mainly attributable to increase in the concave- and convex-shaped synapses. On the contrary, trace eyeblink conditioning resulted in decreases in the thickness of inhibitory PSD. Specifically, these significant changes of PSD thickness were limited to occur in the animals with good behavioral performance. Further analysis of correlations between the trace CR performance and synaptic ultrastructural modifications showed that the thickness of excitatory PSD within the IN correlated with the peak amplitude of trace CRs, whereas the thickness of inhibitory PSD correlated with the onset latency. The present findings suggest that trace eyeblink conditioning induces structural plasticity in the IN, which may play a crucial role in acquiring and executing adaptive eyeblink movements.