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Background/Aims: Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI). The aim of the present study was to evaluate the protective effect of GSK-3β inhibition (TDZD-8) on I/R-induced renal injury through the Nrf2/HO-1 pathway in a streptozocin (STZ)-induced diabetic rat model. Methods: STZ-induced diabetic rats preconditioned with TDZD-8 and ZnPP were subjected to renal I/R. The extent of renal morphologic lesions. Renal function was assessed from blood urea nitrogen (BUN) and serum creatinine (Scr), as determined utlizing commercial kits. Oxidative stress and inflammatory activity in the kidney tissue was estimated from levels of malondialdehyde (MDA), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), as well as the activities of superoxide dismutase (SOD) and glutathione (GSH) using qRT-PCR and ELISA. The expressions of Nrf2, HO-1, Bcl-2 and NF-κB in the renal tissue were measured by qRT-PCR and western blotting. Results: I/R-induced renal inflammation was reduced significantly by TDZD-8 pretreatment. Preconditioning with TDZD-8 suppressed NF-κB expression and enhanced Bcl-2 expression in the renal tissue. The upregulated level of malondialdehyde (MDA), and reduced activities of superoxide dismutase (SOD) and glutathione (GSH) in I/R-shocked rats were markedly restored by TDZD-8 pretreatment. Furthermore, pretreatment with TDZD-8 enhanced activation of the Nrf2/HO-1 pathway in the renal tissue of diabetic RI/RI rats. Conclusion: These findings suggest that preconditioning with TDZD-8 may protect the kidney from I/R-induced damage via the activation of the Nrf2/HO-1 pathway in STZ-induced diabetic rats. Further detailed studies are needed to further clarify the underlying mechanisms.

Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.

Background/Aims: The mammalian skull vault is a highly regulated structure and consists of several membrane bones of different tissue origins (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Although membrane bones form through intramembranous ossification, neural crest derived frontal bone has superior osteoblast activity and bone regeneration ability, triggering a novel conception for craniofacial reconstruction and bone regeneration called endogenous calvarial regeneration. However, a comprehensive landscape of the genes and signaling pathways involved in this process is not clear. Methods: Transcriptome analysis within the two bone elements is firstly performed to determine the physiological signatures of differential gene expressions in mouse skull vault. Results: Frontal bone tissues and parietal bone tissues maintain tissue origin through special gene expression similar to neural crest vs mesoderm tissue, and physiological functions between these two tissues are also found in differences related to proliferation, differentiation and extracellular matrix production and clustered signaling pathways. Conclusion: Our data provide novel insights into the potential gene regulatory network in regulating the development of neural crest-derived frontal bone and mesoderm-derived parietal bone.

Strongly phosphorescent hetero-metallic [2]catenanes, including bimetallic (RCC)12Au6M6 (M = Ag or Cu), (RCC)12Au10Ag2 and trimetallic (RCC)12Au6CunAg6–n, were obtained.

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Supramolecular ensembles adopting ring-in-ring structures are less developed compared with catenanes featuring interlocked rings.W hile catenanes with inter-ring closedshell metallophilic interactions,s uch as d 10 -d 10 Au I -Au I interactions,h ave been well-documented, the ring-in-ring complexes featuring such metallophilic interactions remain underdeveloped. Herein is described an unprecedented ring-inring structure of aA u I -thiolate Au 12 cluster formed by recrystallization of aA u I -thiolate Au 10 [2]catenane from alkane solvents such as hexane,w ith use of ab ulky dibutylfluorene-2-thiolate ligand. The ring-in-ring Au I -thiolate Au 12 cluster features inter-ring Au I -Au I interactions and underwent cluster core change to form the thermodynamically more stable Au 10 [2]catenane structure upon dissolving in, or recrystallization from, other solvents such as CH 2 Cl 2 ,CHCl 3 ,and CH 2 Cl 2 / MeCN.T he cluster-to-cluster transformation process was monitored by 1 HNMR and ESI-MS measurements.D ensity functional theory (DFT) calculations were performed to providei nsight into the mechanism of the "ring-in-ringÐ [2]catenane" interconversions.

Background/Aims: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.