Sequentially degradable hydrogel-microsphere loaded with doxorubicin and pioglitazone synergistically inhibits cancer stemness of osteosarcoma.

Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs) are thought to be the major cause of failure in cancer therapy due to their considerable resistance to most chemotherapeutic agents, resulting in tumor recurrence and eventually metastasis. Here, we report a treatment strategy for osteosarcoma using hydrogel-microspheres (Gel-Mps) complex mainly composed of collagenase (Col) and PLGA microspheres (Mps) carrying Pioglitazone (Pio) and Doxorubicin (Dox). Col was encapsulated in the thermosensitive gel to preferentially degrade tumor extracellular matrix (ECM), ensuring subsequent drug penetration, while Mps with Pio and Dox were co-delivered to synergistically inhibit tumor growth and metastasis. Our results showed that the Gel-Mps dyad functions as a highly biodegradable, extremely efficient, and low-toxic reservoir for sustained drug release, displaying potent inhibition of tumor proliferation and subsequent lung metastasis. Selective PPARγ agonist Pio reversed drug resistance to Dox by significantly down-regulating the expression of stemness markers and P-glycoprotein (P-gp) in osteosarcoma cells. The Gel@Col-Mps@Dox/Pio exhibited advanced therapeutic efficacy in vivo, demonstrating its great potential to serve a novel osteosarcoma therapy, which not only inhibits the growth of, but also attenuates the stemness of osteosarcoma. The dual effects reinforce the sensitivity and efficacy of chemotherapy.

The Quantitative Trait Loci Mapping of Rice Plant and the Components of Its Extract Confirmed the Anti-Inflammatory and Platelet Aggregation Effects In Vitro and In Vivo.

Unpredictable climate change might cause serious lack of food in the world. Therefore, in the present world, it is urgent to prepare countermeasures to solve problems in terms of human survival. In this research, quantitative trait loci (QTLs) were analyzed when rice attacked by white backed planthopper (WBPH) were analyzed using 120 Cheongcheong/Nagdong double haploid lines. Moreover, from the detected QTLs, WBPH resistance-related genes were screened in large candidate genes. Among them, OsCM, a major gene in the synthesis of Cochlioquinone-9 (cq-9), was screened. OsCM has high homology with the sequence of chorismate mutase, and exists in various functional and structural forms in plants that produce aromatic amino acids. It also induces resistance to biotic stress through the synthesis of secondary metabolites in plants. The WBPH resistance was improved in rice overexpressed through map-based cloning of the WBPH resistance-related gene OsCM, which was finally detected by QTL mapping. In addition, cq-9 increased the survival rate of caecal ligation puncture (CLP)-surgery mice by 60%. Moreover, the aorta of rat treated with cq-9 was effective in vasodilation response and significantly reduced the aggregation of rat platelets induced by collagen treatment. A cq-9, which is strongly associated with resistance to WBPH in rice, is also associated with positive effect of CLP surgery mice survival rate, vasodilation, and significantly reduced rat platelet aggregation induced by collagen treatment. Therefore, cq-9 presents research possibilities as a substance in a new paradigm that can act on both Plant-Insect in response to the present unpredictable future.

Application of dexmedetomidine-assisted intravertebral anesthesia in hip replacement and its influence on T-lymphocyte subsets.

Application of dexmedetomidine-assisted intravertebral anesthesia for elderly patients with hip replacement and its influences on T-lymphocyte subsets in peripheral blood were assessed. Eighty-six patients undergoing intravertebral anesthesia in hip replacement were treated as group A, and one hundred patients undergoing intravertebral anesthesia combined with dexmedetomidine were treated as group B. Hemodynamic changes in both groups were compared 5 min before anesthesia (T0), immediately after skin incision (T1) and after surgery (T2). General operation conditions of patients in both groups were recorded. T-lymphocyte subsets, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), visual analogue scale (VAS) pain scores and mini-mental state examination (MMSE) cognitive function changes before surgery and 24 h after surgery were compared between the groups, and the incidence of complications in both groups after 24 h was recorded. The recovery time of patients in group B was shorter than that of group A (P<0.05). Changes of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate fluctuations in group B were lower than those in group A (P<0.05). At 24 h after surgery, VAS scores of group B were lower than those of group A (P<0.05); levels of IL-6 and TNF-α were lower than those of group A (P<0.05); CD3+ cells, CD4+ cells, CD8+ cells, and CD4/CD8 ratio were higher than those of group A (P<0.05), and MMSE score was higher than that of group A (P<0.05). The incidence of gastrointestinal reactions and postoperative cognitive dysfunction (POCD) in group B was lower than that in group A (P<0.05). In conclusion, administration of dexmedetomidine can effectively shorten the recovery time of patients, stabilize intraoperative hemodynamics of patients, protect immune function, and reduce postoperative pain and POCD occurrence during anesthesia of hip replacement.

Protective efficacy of combined use of parecoxib and dexmedetomidine on postoperative hyperalgesia and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients.

PURPOSE: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. METHODS: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. RESULTS: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. CONCLUSION: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.

Protective efficacy of combined use of parecoxib and dexmedetomidine on postoperative hyperalgesia and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients

Abstract Purpose: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. Methods: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. Results: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. Conclusion: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.