Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA

Retirement : should you be worried?

The Central Provident Fund (CPF) is Singapore’s national saving system and contributions to CPF accounts are as high as 36% of a person’s wage. Previous studies on adequacy of CPF for retirement spending focused on the Income Replacement Rate (IRR) as the metric for measuring adequacy, but among them there is little agreement on the final IRR achievable by CPF. Furthermore, the inception of the new CPF Life scheme has rendered previous studies outdated. In this report, we propose a different quantitative approach to the question of adequacy, which is to model an individual’s savings and retirement expenditure using publicly available data, and determine if the accumulated wealth is sufficient to cover retirement spending. We find out that the CPF Life income can adequately cover retirement expenses for the 30th percentile of income earners. Therefore, CPF Life serves its purpose as a source of post-retirement funds for the lower-income group. However, adverse changes in wage growth rate or inflation rate can lead to the 30th percentile not being able to cover their retirement expenses even with personal savings. Meanwhile, the statutory Minimum Sum level may need to be reviewed as it is more than enough to sustain basic expenses after retirement.BUSINES

Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction

Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction

STAT6 degradation and ubiquitylated TRIML2 are essential for activation of human oncogenic herpesvirus.

Aberrations in STAT6-mediated signaling are linked to the development of multiple cancer types. Increasing evidence has shown that activation of human oncogenic herpesvirus lytic replication is crucial for viral tumorigenesis. However, the role of STAT6 in herpesvirus lytic replication remains elusive. Here, by using Kaposi's sarcoma-associated herpesvirus (KSHV) as a model, we revealed that RTA, the master regulator of lytic replication, interacts with STAT6 and promotes lysine 48 (K48) and K63-linked ubiquitylation of STAT6 for degradation via the proteasome and lysosome systems. Moreover, degradation of STAT6 is dramatically associated with the increased ubiquitylated form of tripartite motif family like 2 (TRIML2, a tumor suppressor) for prolonged cell survival and virion production, which is also commonly observed in lytic activation of Epstein-Barr virus, herpes simplex virus 1 and cytomegalovirus. These results suggest that degradation of STAT6 is important for the lytic activation of KSHV and as such, may be an attractive therapeutic target

Membrane Surface Modification and Functionalization

Surface functionalization of membranes is one of the efficient techniques that can bestow these membranes with novel properties and transform them into valuable finished products. It has been widely applied to polymeric membranes in many fields and has progressed rapidly in recent years. The modified membranes have been widely used in various applications, such as in separation processes for liquid and gaseous mixtures (gas separation, reverse osmosis, pervaporation, nanofiltration, ultrafiltration, microfiltration), biomaterials, catalysis (including fuel cell systems), and “smart” membranes. In this chapter, various approaches to the surface modification and functionalization of polymeric membranes are highlighted and reviewed. Also, the applications of the modified membranes will be discussed from the aspect of environmental stimuli-responsive gating membranes, antifouling membranes, adsorption membranes, pervaporation and reverse osmosis membranes, membranes for energy conversion, gas separation membranes, and biomedical membranes. A detailed overview of the usage of polyzwitterions and oxidative stability of surface modifiers to alter membrane surface charge will be outlined. Finally, recent advances and developments in surface modification techniques such as layer-by-layer assembly and chemical vapor deposition will be discussed