ABSTRACT
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
ABSTRACT
Objective To investigate the effect and mechanisms of pioglitazone on post operative cognitive function induced by surgery in elderly rats.Methods Elderly SD rats,male and weighing 220-250 g,were randomly divided into control group (group Con),surgery group (group S),pioglitazone group (group P)and pioglitazone/surgery group (group PS).The level of glycemia was measured by glucometer after completing the surgical model.The expression of advanced glycation endproducts (AGEs)in hippocampal tissues was detected by western blot and reactive oxy-gen species (ROS)and IL-6 by ELISA 1 2 h after surgery.Morris water maze was used for evaluation of cognitive function 4 days after surgery.Results Compared with group Con,group S showed a sig-nificant increase in the expression of AGEs and IL-6 and the level of ROS (P<0.05);Compared with group S,the expression of AGEs and IL-6 and the level of ROS decreased significantly in group PS (P<0.05).Compared to group Con,the surgery increased the average time of escape latencies on the 8th days and 10th days after surgery and reduced the platform-crossing times in the Morris water maze test (P<0.05).Compared with group S,group PS showed a significant decrease in the average time of escaping latencies on the 10th day after surgery (P<0.05),and an increased platform-cross-ing times in the Morris water maze test (P<0.05).Conclusion These results suggest that pioglita-zone attenuates postoperative cognitive function and its mechanism may be related to the decrease of the expression of AGEs and IL-6 and the level of ROS.
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Objective To evaluate the role of μ-δ heterodimer in down-regulation of the expression of excitatory amino acid transporter 3 (EAAT3) in hippocampi caused by reinstatement of morphine-induced conditioned place preference (CPP) in rats.Methods Thirty-two healthy clean-grade male Sprague-Dawley rats,weighing 200-240 g,were assigned into 4 groups (n =8 each) using a random number table method:control group (group C),extinction group (group E),reinstatement group (group R) and reinstatement plus interference plasmid group (group RI).The model of morphine-induced CPP was established,and extinction of CPP was gradually induced by stopping administration.A small dose of morphine 5 mg/kg was intraperitoneally injected again to induce CPP reinstatement,and dwell time around the medicine box was recorded.μ-δ heterodimer interference plasmid 5 μl was injected into the lateral cerebral ventricle after successful establishment of CPP model in group RI.The content of glutamate (Glu) in hippocampi was measured using high-performance liquid chromatography.The EAAT3 expression in hippocampal CA1 and CA3 regions was detected using Western blot.Results Compared with group C,no significant change was found in the dwell time around the medicine box or content of Glu in hippocampi (P＞0.05),and the expression of EAAT3 in hippocampal CA1 and CA3 regions was significantly up-regulated in group E,and the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased (P＜0.05),and no significant change was found in the expression of EAAT3 in hippocampal CA1 and CA3 regions in group R (P＞0.05).Compared with group E,the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased,and the expression of EAAT3 in hippocampal CA1 and CA3 regions was down-regulated in group R (P＜0.05).Compared with group R,the dwell time around the medicine box was significantly shortened,the content of Glu in hippocampi was decreased,and the expression of EAAT3 in hippocampal CA 1 and CA3 regions was upregulated in group RI (P＜0.05).Conclusion μ-δ heterodimer is involved in down-regulation of EAAT3 expression in the hippocampus caused by reinstatement of morphine-induced CPP in rats.
ABSTRACT
BACKGROUND:Alveolar distraction osteogenesis is an important method for treating alveolar bone atrophy, the osteogenesis process and biomechanics play a crucial role in the fol owing implantation and repair. At present, no related experimental studies are found. OBJECTIVE:To analyze the biomechanical and histological characteristics of alveolar distraction osteogenesis in a canine model. METHODS:Twelve adult mongrel canines received premolars extraction and alveoloplasty in mandible to establish an atrophy alveolar model. After 3 months, a segmental alveolar osteotomy was performed in the randomly selected unilateral atrophy alveolar and two intra-osseous distractors were placed. After a 7-days latency period, the alveolar ridge was augmented at a rate of 1.0 mm/d for 5 days. After a consolidation of 1, 2, and 3 months, the canines were sacrificed and the specimens of the distracted alveolar bone were harvested for clinical, radiographic, histological and biomechanical analysis. RESULTS AND CONCLUSION:The alveolar distractors obtained good healing with surrounding tissue. The atrophy alveolar bones were augmented for (4.80±0.50) mm and (5.12±0.47) mm by clinical and radiographic findings immediately after distraction, respectively. The bone trabeculae in the distracted chamber matured from 1 to 3 months of consolidation by histological analysis. The shearing force of alveolar distraction chamber increased from 1 to 3 months. After 3 months’ consolidation, the shearing force of distracted chamber was comparable to host bone. The histological and biomechanical property of distracted alveolar chamber is comparable to host bone after 3 months’ consolidation.