Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic, hormonal, mechanical and ageing factors affect its progression. Current studies are focusing on chondrocytes as a key mediator of OA at a cellular level. however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is involved in a large number of physiological and pathological processes. In the present study, we examined whether PUMA has a role in IL-1β-induced apoptosis and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the induction of PUMA, thus contributing to chondrocyte apoptosis. The results demonstrated an increase in PUMA protein and mRNA levels in cultured mouse chondrocytes following 4 h of IL-1β treatment. Furthermore, this upregulation of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA-specific siRNA significantly reduced apoptosis in cultured cells. Upon pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the expression of PUMA was notably suppressed with a concomitant decrease in apoptosis observed in IL-1β-treated chondrocytes. Also, immunohistochemical studies revealed that the PUMA and c-Jun proteins were upregulated in chondrocytes from the articular cartilage of OA patients. Together, these data suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of chondrocyte apoptosis during OA.
Ginseng fruit saponins (GFS) extracted from the ginseng fruit are the bioactive triterpenoid saponin components. The aim of the present study was to develop a drug delivery system called proliposome using sodium deoxycholate (NaDC) as a bile salt to improve the oral bioavailability of GFS in rats. The liposomes of GFS were prepared by a conventional ethanol injection and formed the solid proliposomes (P-GFS) using spray drying method on mannitol carriers. The formulation of P-GFS was optimized using the response surface methodology. The physicochemical properties of liposome suspensions including encapsulation efficiency, in vitro drug release studies, particle size of the reconstituted liposome were tested. The solid state characterization studies using the method of Field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) and Differential scanning colorimetric (DSC) were tested to study the molecular state of P-GFS and to indicate the interactions among the formulation ingredients. In vitro studies showed a delayed release of ginsenoside Re (GRe). In vivo studies were carried out in rats. The concentrations of GRe in plasma of rats and its pharmacokinetic behaviors after oral administration of GFS, Zhenyuan tablets (commercial dosage form of GFS) and P-GFS were studied using ultra performance liquid chromatography tandem mass spectrometry. It was founded that the GRe concentration time curves of GFS, Zhenyuan tablets and P-GFS were much more different in rats. Pharmacokinetic behaviors of P-GFS showed a second absorption peak on the concentration time curve. The pharmacokinetic parameters of GFS, Zhenyuan tablets, P-GFS in rats were separately listed as follows: T max 0.25 h, C max 474.96 ± 66.06 ng/ml and AUC0-∞ 733.32 ± 113.82 ng/ml h for GFS; T max 0.31 ± 0.043 h, C max 533.94 ± 106.54 ng/ml and AUC0-∞ 1151.38 ± 198.29 ng/ml h for Zhenyuan tablets; T max 0.5 h, C max 680.62 ± 138.051 ng/ml and AUC0-∞ 2082.49 ± 408.33 ng/ml h for the P-GFS. The bioavailability of P-GFS was nearly 284% and 181% of the GFS and Zhengyuan tablets respectively. In conclusion, the proliposomes significantly enhanced the drug bioavailability, absorption in the gastrointestinal tract and decreased its elimination time of GRe in rats and could be selectively applied for oral delivery of GFS.
The concept of virtual water, as a new approach for addressing water shortage and safety issues, can be applied to support sustainable development in water-scarce regions. Using the input-output method, the direct and the complete water use coefficients of industries categorized as primary, secondary, or tertiary, and the spatial flow patterns of the inter-provincial trade in the Gansu province region of China, were explored. The results show that in 2007, 2010, and 2012 the direct and complete water use coefficients of the primary industries were the greatest among the three industry categories, with direct water use coefficients of 1545.58, 882.28, and 762.16, respectively, and complete water use coefficients of 1692.22, 1005.38, and 873.44, respectively; whereas, the direct and complete water use coefficient values of the tertiary industry category were the lowest, with direct water use coefficients of 16.65, 7.74, and 66.89 for 2007, 2010, and 2012, respectively, and complete water use coefficients of 65.46, 66.89, and 72.81 for 2007, 2010, and 2012, respectively. In addition, study results suggest that the volume of virtual water supplied to Gasnu province’s local industries has decreased annually, while virtual water exports from the province have increased annually, with the primary industry accounting for 95% of virtual water output. Overall, the virtual water of Gansu province in 2010 showed a net output trend, with a total output of 0.506 billion m3, while in 2007 and 2012 it showed a net input trend with a total input of 0.104 and 1.235 billion m3, respectively. Beijing, Shanghai, Guangdong, Ningxia and other water-scarce areas were the main input, or import source for Gansu’s virtual water; during the years studied, these provinces imported more than 50 million m3 individually. Based on these results, it is clear that under the current structure, virtual water is mainly exported to the well-developed coastal areas and their adjacent provinces or other water-abundant regions. Therefore, Gansu province should (1) adjust the industrial structure and develop water-saving and high-tech industries; (2) adjust the current trade pattern to reduce virtual water output while increasing its input to achieve balanced economic development and water resource security.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.