Polyamine derivatives have a promising prospect in dealing with disseminated tumor cells, a major obstacle in cancer therapy. To develop a bifunctional polyamine derivative that can serve as a ...fluorescent probe and an antimetastatic agent, three kinds of polyamine conjugates with benzocdindol-2(1H)-one as a scaffold were designed and synthesized. Compound 5e was selected as a lead by in vitro screening. Two animal models demonstrated that 5e inhibited pulmonary metastasis and tumor growth. As a fluorescent probe, 5e might partially enter cells via a polyamine transporter and subsequently localize in the lysosome. Mechanistic investigations demonstrated the interdependence of 5e-triggered apoptosis and autophagy. Compound 5e modulated the expression of LC3-II, p62, cathepsins, and the expression of capases 3, caspase 8, Bcl-2, and p53. The SSAT-mediated Akt/β-catenin pathways were also inhibited by 5e. The dual features of 5e make it a worthwhile lead compound for further structural optimization.
This paper reviews the best known techniques using circular dichroism spectroscopy such as conventional circular dichroism (i.e. electronic circular dichroism), magnetic circular dichroisms (magnetic ...vibrational circular dichroism, x‐ray magnetic circular dichroism), fluorescence detected circular dichroism, near‐infrared circular dichroism, vibrational circular dichroism, Fourier transform infrared circular dichroism, high pressure liquid chromatography circular dichroism, stopped‐flow circular dichroism, and synchrotron radiation circular dichroism. Also, we have described here the most important applications of circular dichroism spectroscopy in structural biochemistry and nanoscience.
Silicon spraying on leaves can reduce the accumulation of cadmium (Cd) in rice grain. However, it has been found that not all rice varieties decrease in Cd content after silicon (Si) application. A ...field study was conducted to check the performance of Si on the accumulation and transport of Cd in four rice varieties. TY390 and YXY2, having 51.5%− 60.6% Cd content of grain was inhibited by foliar Si, were classified as CRS varieties; BXY9978 and YXYLS, having Cd content of grain is nonresponsive with Si, were classified as CNS varieties. The Cd contents were mainly accumulated in stem, especially in the first stem node. While foliar Si reported no changes in the Cd content of first node in four different rice varieties. Comparing the correlation between Si and Cd contents in the above part of the first internode of CRS and CNS, as well as the relative expression of Cd transport genes in the first internode suggested that first internode was the key site to effect Cd transport through Si application, and OsZIP7 is a key Cd transporter protein responsive to Si, leading to different response of Cd transport and accmulation between the CRS and the CNS varieties of rice.
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•Response of different rice varieties to Si mainly lies in the first internode.•OsZIP7 is the key Cd transporter responding to Silicon.•+Si treatment regulates genes of Cd transporter protein in inhibited varieties.•Application of Si reduced the transport of Cd to grain of inhibited varieties.•+Si has a positive effect on the Si transporter in the inhabited varieties.
Atmospheric deposition of heavy metals such as Cd is a threat to ecosystems and food safety. Our knowledge is still limited about the effectiveness of remediation process for Cd-contaminated ...agro-soils under atmospheric Cd deposition. In this study, eight soil amendments were used in a Cd-contaminated purple soil to investigate their impacts on soil Cd availability, microbial response, and Cd uptake by mustard and corn plants via simulating the atmospheric Cd deposition under laboratory incubation and greenhouse conditions. Results showed that the simulated atmospheric Cd deposition increased the soil high-risk Cd (HR, exchangeable and carbonate Cd) and decreased soil medium-risk Cd fraction (MR, bound to Fe/Mn oxide and organic Cd), and the largest direct effects on crop Cd uptakes were 0.94 and 0.66 for mustard and corn based on the path-coefficient analysis, respectively. Generally, Cd deposition led to decreasing soil microbial biomass carbon, populations of bacteria, fungi and actinomycetes, and enzyme activities of urease, catalase, sucrase, and acid phosphatase whereas increasing soil microbial biomass nitrogen. Compared with control and lime treatments, an organic-inorganic combined preparation (OCP) appeared to be effective for remediation of the Cd-contaminated purple soil due to its potential to increase the HR-Cd and reduce both MR-Cd and crop Cd uptake, as accompanied by its neutral effects on soil bacterial alpha diversity and community structure. Results also indicated that application of nitrogen fertilizers should be considered for remediation of the Cd-contaminated soils as nitrogen inputs were demonstrated to promote soil health under elevated Cd condition.
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•Atmospheric Cd deposition was explored firstly in Cd-contaminated soil remediation.•Direct effects of deposited Cd on Cd uptakes of mustard and corn were quantified.•Optimum amendment was made for Cd-contaminated purple soil exposed to Cd deposition.•Different responses of soil microbiome to simulated Cd deposition.•Nitrogen fertilizer should be considered during the Cd-contaminated soil remediation.
Pot experiments were conducted to investigate the impacts of continuous addition of different concentrations of calcium chloride (CaCl2) and/or low-molecular-weight organic acids (LMWOAs) on soil pH, ...electrical conductivity (EC), and cadmium (Cd) transformation. These factors subsequently affected Cd phytoavailability in a system consisting of Cd-contaminated soil and Chinese cabbage (Brassica chinensis L.). The results indicate that CaCl2 addition had a greater impact on reducing soil pH value, increasing soil EC value, and enhancing Cd phytoaccumulation in Chinese cabbage compared to LMWOAs. When soil pH dropped by 0.3 unit and the soil EC increased by 500 µS cm−1, the Cd concentration in the Chinese cabbage shoots was 3 times higher than that in the control group. Throughout two planting terms of Chinese cabbage, the addition of CaCl2 (1.6–3.2 g kg−1) and LMWOAs (≤ 1.0 g kg−1) led to phytoextracted Cd concentration exceeding exchangeable Cd concentration in soil samples before the pot experiment. Regarding phytoextracted Cd, desorption from carbonate-bound Cd contributes more than desorption from bound to organic matter Cd and adsorption to Fe/Mn oxide Cd. This study underscores the influence of soil pH and EC value variations and Cd transformation on Cd phytoavailability. Special attention should be given to leafy vegetables grown in Cd-contaminated soil, as the phytoavailable Cd concentration reaches approximately 2.0 µg kg−1, which may lead to Cd levels surpassing acceptable limits for Chinese cabbage.
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•Soil pH fell by 0.3 and EC rose by 0.5 dS m− 1 causing 3 times of CCd in Chinese cabbage.•Cd transformation between Cd fractions affects the phytoextracted Cd from soil.•Phytoavailable of CCd at 2.0 µg kg− 1 in soil may lead to 0.2 mg kg− 1 of CCd in Chinese cabbage.•Soil Cd threshold for food safety should be re-established based on phytoavailable Cd.
Cadmium (Cd), which seriously affects plant growth and crop production, is harmful to humans. Previous studies revealed ryegrass (Lolium multiflorum Lam.) exhibits Cd tolerance, and may be useful as ...a potential hyperaccumulator because of its wide distribution. In this study, the physiological and transcriptional responses of two ryegrass cultivars i.e., high (LmHC) and low (LmLC) Cd tolerance to Cd stress were investigated and compared. The Cd tolerance of LmHC was greater than that of LmLC at various Cd concentrations. The uptake of Evans blue dye revealed that Cd-induced root cell mortality was higher in LmLC than in LmHC after a 12-h Cd treatment. Furthermore, the content and influx rate of Cd in LmLC roots were greater than in LmHC roots under Cd stress conditions. The RNA sequencing and quantitative real-time PCR data indicated that the Cd transport regulatory genes (ABCG37, ABCB4, NRAMP4, and HMA5) were differentially expressed between the LmLC and LmHC roots. This expression-level diversity may contribute to the differences in the Cd accumulation and translocation between LmLC and LmHC. These findings may help clarify the physiological and molecular mechanisms underlying ryegrass responses to Cd toxicity. Additionally, ryegrass may be able to hyperaccumulate toxic heavy metals during the phytoremediation of contaminated soil.
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•The Cd tolerance of LmHC was stronger than LmLC.•The influx rate and accumulation of Cd in the LmLC roots were greater than LmHC.•Up-regulated expression of ABCG37, ABCB4, and ABCB21 might improve Cd uptake.•LmLC is a potential hyperaccumulator for bioremediation of soil contaminated with Cd.
LAG3 (CD223) as a cancer immunotherapy target Andrews, Lawrence P.; Marciscano, Ariel E.; Drake, Charles G. ...
Immunological reviews,
March 2017, 2017-03-00, 20170301, Volume:
276, Issue:
1
Journal Article
Peer reviewed
Open access
Summary
Despite the impressive impact of CTLA4 and PD1‐PDL1‐targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to ...targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene‐3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity. However, persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression, contributing to a state of exhaustion manifest in impaired proliferation and cytokine production. The exact signaling mechanisms downstream of LAG3 and interplay with other IRs remain largely unknown. However, the striking synergy between LAG3 and PD1 observed in multiple settings, coupled with the contrasting intracellular cytoplasmic domain of LAG3 as compared with other IRs, highlights the potential uniqueness of LAG3. There are now four LAG3‐targeted therapies in the clinic with many more in preclinical development, emphasizing the broad interest in this IR. Given the translational relevance of LAG3 and the heightened interest in the impact of dual LAG3/PD1 targeting in the clinic, the outcome of these trials could serve as a nexus; significantly increasing or dampening enthusiasm for subsequent targets in the cancer immunotherapeutic pipeline.
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