A combination of curcumin, vorinostat and silibinin reverses Aβ-induced nerve cell toxicity via activation of AKT-MDM2-p53 pathway

Alzheimer’s disease (AD) is a significant health issue for the elderly and becoming increasingly common as the global population ages. Although many efforts have been made to elucidate its pathology, there is still a lack of effective clinical anti-AD agents. Previous research has shown the neuroprotective properties of a combination of curcumin and vorinostat. In this study, nine other neuroprotective agents were investigated to examine whether a three-drug combination of curcumin, vorinostat, and a new drug is more advantageous than the previous two-drug combination in alleviating amyloid beta (Aβ)-induced nerve cell toxicity. Cell viability assay was performed to screen these agents, and further validation tests, including determination of cellular oxidative stress, apoptosis, and activity of the AKT/MDM2/p53 pathway, were performed. Among the nine candidate compounds, only silibinin at 1 µM reduced Aβ25–35-induced toxicity in PC12 cells. The neuroprotective effects of 1 µM silibinin in combination with 5 µM curcumin and 0.5 µM vorinostat (CVS) was shown in PC12 cells, in which it decreased apoptosis and oxidative stress marker levels that were increased by 20 µM Aβ25–35. Western blotting results showed that CVS pretreatment significantly increased the phosphorylation of AKT, BAD, and MDM2, which resulted in decreased intracellular expression of p53. Further, immunofluorescence results showed reduced p53 levels in the nuclei of PC12 cells following CVS pretreatment, indicating a reduction in the p53-mediated transcriptional activity associated with Aβ25–35 exposure. In conclusion, our findings suggested that pretreatment with CVS protected PC12 cells from Aβ25–35-induced toxicity through modulation of the AKT/MDM2/p53 pathway. Thus, CVS may present a new therapeutic option for treating AD

Residual dynamics and dietary exposure risk of dimethoate and its metabolite in greenhouse celery

This study aimed to explore the residual dynamics and dietary risk of dimethoate and its metabolite omethoate in celery. Celery was sprayed with 40% dimethoate emulsifiable concentrate (EC) at either a low concentration of 600 g a.i./ha or a high concentration of 900 g a.i./ha. Plants in the seedling, transplanting, or middle growth stages were sprayed once, and the samples were collected 90 days after transplantation. Plants in the harvesting stage were sprayed two or three times. The samples were collected on days 3, 5, 7, 10, 14 and 21 after the last pesticide application. The dimethoate and omethoate compounds were extracted from the celery samples using acetonitrile, and their concentrations were detected using ultra-performance liquid chromatography-tandem mass spectrometry. Also, the dietary risk assessments of dimethoate and omethoate were conducted in various populations and on different foods in China. The metabolism led to the formation of omethoate from dimethoate in the celery. The degradation dynamics of dimethoate and total residues in greenhouse celery followed the first-order kinetic equation. The half-lives of the compounds were 2.42 days and 2.92 days, respectively. The celery which received one application during the harvesting stage had a final residue of dimethoate after 14 days, which was lower than the maximum residue limit (MRL) 0.5 mg kg−1 for Chinese celery. The final deposition of the metabolite omethoate after 28 days was less than the maximum residue limit of 0.02 mg kg−1 for Chinese celery. Furthermore, the risk quotients of dimethoate in celery were less than 1; therefore, the level of chronic risk was acceptable after day 21. Only children aged 2–7 years had an HQ of dimethoate more than 1 (an unacceptable level of acute risk), while the acute dietary risks to other populations were within acceptable levels. It was recommended that any dimethoate applications to celery in greenhouses should happen before the celery reached the harvesting stage, with a safety interval of 28 days

Decreased osteogenesis of adult mesenchymal stem cells by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis

Age related defect of the osteogenic differentiation of mesenchymal stem cells (MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation. Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats. Accordingly, there were much more reactive oxygen species (ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1 (SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability

Evaluating Water Management Efficiency in Regulating Cadmium and Arsenic Accumulation in Rice in Typical Japonica Paddy Soils at Varied pH Levels

There is growing concern regarding cadmium (Cd) exposure through rice consumption. Compared with alternate wetting and drying (AWD), continuous flooding (CF) is usually considered as an effective approach for reducing Cd enrichment in rice but increases the risk of pollution from arsenic (As). In this study, the field trial was conducted to investigate remediation effects of two water management (CF and AWD) techniques on Cd pollution in rice in typical japonica rice cultivation areas with varied soil pH levels. The results indicate that soil pH was a crucial factor in regulating CF-mediated Cd/As accumulation and migration in rice plants, and grains at all stages of rice growth. In acidic fields, compared with AWD, the use of CF reduced the accumulation of Cd in plants during the tillering stage; CF during the milk stage promotes the risk of contamination of Cd in rice grains and any form of As in plants and inhibits the content of any forms of As in grains. During the mature stage, CF reduced the levels of Cd in the plants and grains while promoting the accumulation of As(V) and total As(T-As) in plants and As(III) in grains. In alkaline fields, compared with AWD, CF during the tillering stage promoted the accumulation of various forms of As in plants. During the milk stage, CF increased and decreased the Cd content in plants and grains, respectively, and reduced the accumulation of T-As in plants and As(III) in grains; during the mature stage, CF promoted the accumulation of Cd in plants and grains, induced the accumulation of T-As plants, and inhibited the accumulation of any form of As in grains. From the perspective of food safety, the impact of CF conditions on the accumulation of Cd and As in rice from acidic fields exhibited a pattern of reduction in Cd and increase in As during the maturity period, as compared to that on the AWD. Conversely, CF increased the Cd risk while simultaneously reducing the As accumulation in rice grains to a safe level in alkaline fields. CF is not recommended as a remediation strategy for Cd pollution in rice in low Cd pollution areas, but it can be considered as a potential strategy for As pollution remediation in rice in alkaline fields with low Cd pollution

Effects of exogenous salicylic acid on accumulation of camptothecin and gene expression in Camptotheca acuminata Decne

Camptotheca acuminata Decne (Nyssaceae) is major natural source of camptothecin, an anticancer drug widely used for clinic therapy. Previous works have shown that many plant hormones/elicitors could regulate camptothecin biosynthesis, but few reports have examined sustanable effects of these plant hormones on plants for producing camptothecin. In this work, seedlings obtained from in vitro rapid propagation were used for investigating sustainable effect of Salicylic acid (SA) on transplanted C. acuminata tissues, especially leaves, for camptothecin biosynthesis. Our results indicate that exogenous SA could continuously induce the expression of iridoids pathway genes in C. acuminata leaves for promoting camptothecin production. After transplanted to soil for 180 days, high expression of iridoids pathway genes still could be observed in bioactive young leaves. In C. acuminata, iridoids pathway genes are expressed at very low levels or not detectable in old leaves, which lead to inefficient production of camptothecin with leaf development. Interestingly, the expression of these genes could be clearly detected in old leaves of transplanted C. acuminata pretreated with 10 ÂľM of SA during in vitro rapid propagation phase, which indicates particular function of SA for sustainable effect on maintaining relative high expression levels of iridoids pathway genes for camptothecin biosynthesis.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Review on the Applications and Molecular Mechanisms of Xihuang Pill in Tumor Treatment

Xihuang pill (XH) is a complementary and alternative medicine that has been used in traditional Chinese medicine (TCM) for the treatment of tumors since the 18th century. XH has clinical effects on non-Hodgkin lymphoma, breast cancer, gastric cancer, liver cancer, and bone metastasis. XH can also inhibit the growth of tumor cells and cancer stem cells, prevent tumor invasion and angiogenesis, and regulate the tumor microenvironment. XH is composed of Ru Xiang (olibanum), Mo Yao (Commiphora myrrha), She Xiang (Moschus), and Niu Huang (Calculus bovis). Some of the compounds found in these ingredients exert multiple antitumor effects and may synergize with the other ingredients. We aimed to summarize the clinical applications and molecular mechanisms of XH and its chemical composition. This review will provide potential new strategies and alternative perspectives for tumor treatments and basic research into complementary and alternative medicine

Enhanced Rice Resistance to Sheath Blight through <i>Nitrate Transporter 1.1B</i> Mutation without Yield Loss under NH₄⁺ Fertilization

Nitrogen fertilization can promote rice yield but decrease resistance to sheath blight (ShB). In this study, the nitrate transporter 1.1b (nrt1.1b) mutant that exhibited less susceptibility to ShB but without compromising yield under NH4+ fertilization was screened. NRT1.1B’s regulation of ShB resistance was independent of the total nitrogen concentration in rice under NH4+ conditions. In nrt1.1b mutant plants, the NH4+ application modulated auxin signaling, chlorophyll content, and phosphate signaling to promote ShB resistance. Furthermore, the findings indicated that NRT1.1B negatively regulated ShB resistance by positively modulating the expression of H+-ATPase gene OSA3 and phosphate transport gene PT8. The mutation of OSA3 and PT8 promoted ShB resistance by increasing the apoplastic pH in rice. Our study identified the ShB resistance mutant nrt1.1b, which maintained normal nitrogen use efficiency without compromising yield

Enhanced Rice Resistance to Sheath Blight through <i>Nitrate Transporter 1.1B</i> Mutation without Yield Loss under NH₄⁺ Fertilization

Nitrogen fertilization can promote rice yield but decrease resistance to sheath blight (ShB). In this study, the nitrate transporter 1.1b (nrt1.1b) mutant that exhibited less susceptibility to ShB but without compromising yield under NH4+ fertilization was screened. NRT1.1B’s regulation of ShB resistance was independent of the total nitrogen concentration in rice under NH4+ conditions. In nrt1.1b mutant plants, the NH4+ application modulated auxin signaling, chlorophyll content, and phosphate signaling to promote ShB resistance. Furthermore, the findings indicated that NRT1.1B negatively regulated ShB resistance by positively modulating the expression of H+-ATPase gene OSA3 and phosphate transport gene PT8. The mutation of OSA3 and PT8 promoted ShB resistance by increasing the apoplastic pH in rice. Our study identified the ShB resistance mutant nrt1.1b, which maintained normal nitrogen use efficiency without compromising yield