ABSTRACT
Pollution caused by Copper and hydrogen sulfide pollution has severe adverse effects on the environment and organisms. Real-time, fast and accurate monitoring of Cu2+ and S2- faces serious challenges. In this study, we designed a novel biosensor and synthesized it by mimicking the structure of the main Cu(II)-binding site on bovine serum albumin. As a peptide-based sensor, FGGH (FITC-Gly-Gly-His-NH2) can perform the sequential detection of Cu2+ and S2- by fluorescence and colorimetry. The high water solubility and selectivity make it suitable for monitoring Cu2+ and S2- in environmental water samples with high sensitivity; its limit of detection (LOD) is as low as 1.42 nM for Cu2+ and 22.2 nM for S2-. The paper-based sensing platform of this probe was found to be a promising tool for the on-site visualization of real-time quantitative analysis of Cu2+ and S2- due to its rapid response and recyclable detection characteristics. Additionally, FGGH was successfully used to image Cu2+ and S2- in living cells and zebrafish models with adequate fluorescence stability and low cytotoxicity, providing the first visual evidence of the effect of the interactions between Cu2+ and S2- on the redox homeostasis of organisms.
Subject(s)
Colorimetry , Copper , Animals , Copper/chemistry , Colorimetry/methods , Fluorescent Dyes/chemistry , Zebrafish , Peptides/chemistry , Water/chemistry , Spectrometry, Fluorescence/methodsABSTRACT
Mercury is a harmful heavy metal that seriously threatens the environment and organisms. In this study, we combined the aggregation-induced emission mechanism and the advantages of peptides to design a novel tetraphenylene (TPE)-based peptide fluorescent probe, TPE-Cys-Pro-Gly-His (TPE-CPGH), in which the sulfhydryl group of Cys in the peptide chain and the imidazolium nitrogen provided by His were used to mimic the Hg2+ binding site of metalloproteins. The ß-fold formed by Pro-Gly was used to promote the spatial coordination of the probe with Hg2+ and the formation of the coordination complex aggregates, these changes led to the "turn on" response to Hg2+. The detection of Hg2+ by TPE-CPGH not only showed high specificity and sensitivity (LOD=46.2 nM), but also had the advantages of fast response and applicability for detection over a wide pH range. Additionally, TPE-CPGH effectively detected Hg2+ in environmental samples, living cells and organisms due to its low cytotoxicity, high water solubility and cell membrane permeability. More interestingly, TPE-CPGH was also mitigated Hg2+ exposure-induced oxidative stress toxicity in vitro and in vivo.
Subject(s)
Mercury , Metals, Heavy , Fluorescent Dyes/chemistry , Limit of Detection , Peptides/chemistry , Spectrometry, FluorescenceABSTRACT
Treatment of neuropathic pain is far from satisfactory. This study sought evidence of a neuroprotective effect of alpha-lipoic acid (ALA) to treat neuropathic pain in a chronic constriction injury (CCI) rat model. A total of 48 rats were randomly divided into sham, CCI, or CCI + ALA groups. Mechanical and thermal nociceptive thresholds were evaluated as behavioral assessments. Dorsal root ganglia cells were assessed morphologically with hematoxylin and eosin staining and for apoptosis with P53 immunohistochemical staining. Compared with the sham group, the CCI group had a shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphologic manifestations, and increased numbers of satellite glial cells and P53+ cells. These changes were significantly reversed by treatment with ALA. Our study indicates neuroprotective effects of ALA on chronic neuropathic pain in a CCI rat model. ALA is potentially considered to be developed as a treatment for neuropathic pain caused by peripheral nerve injury, which requires further verification.
ABSTRACT
INTRODUCTION: Neuropathic pain is pretty common in modern society, and the treatment effect is far from satisfactory. This study aimed to find evidence of the neuroprotective effect of erythropoietin (EPO) in the treatment of neuropathic pain in a rat model of chronic constriction injury (CCI). METHODS: A total of 30 rats were randomly divided into sham operation group, CCI group, or CCI+EPO group. The mechanical and thermal nociception thresholds are evaluated as behavioral assessments. The dorsal root ganglion cells were morphologically evaluated by hematoxylin and eosin staining, and AMPK, p-AMPK, mTOR, p70S6K, and AQP-2 proteins were compared and analyzed by Western blotting. Compared with the sham operation group, rats in the CCI group had shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphology, and increased satellite glial cells. RESULTS: After treatment with EPO, these changes were significantly reversed. In vivo administration of erythropoietin seems to be able to regulate the expression of AQP-2 through the AMPK/mTOR/p70S6K pathway. Our study provides behavioral, morphological, and immunoblot evidence to prove the neuroprotective effect of EPO in the treatment of chronic neuropathic pain in the CCI rat model. CONCLUSION: Our results indicate that EPO has the potential to treat neuropathic pain caused by peripheral nerve injury, although further verification is needed.
ABSTRACT
BACKGROUND: The C-reactive protein to prealbumin ratio (CPR) and prealbumin to fibrinogen ratio (PFR) are two new inflammatory markers that were reported to have predictive value for the assessment of systemic inflammatory disease. The aim of the present study was to explore the relationship between these two markers and the Disease Activity Score of 28 joints (DAS-28) in rheumatoid arthritis (RA). METHODS: A total of 170 RA patients and 120 healthy individuals were enrolled in this retrospective study. Correlations of CPR and PFR with the disease activity of RA were analyzed. Receiver-operating characteristic (ROC) curves for CPR and PFR were generated to determine the discriminative ability by calculating the areas under the curve (AUC). RESULTS: Compared with healthy controls, RA patients showed a significantly lower PFR (p < 0.001) and higher CPR (p < 0.001). CPR was positively correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS-28 score (r = 0.957, p < 0.001, r = 0.781, p < 0.001, r = 0.729, p < 0.001, respectively), whereas the PFR was negatively correlated with CRP, ESR, and DAS-28 score (r = -0.817, p < 0.001, r = -0.805, p < 0.001, r = -0.739, p < 0.001, respectively) in RA patients. ROC curve analysis showed that the CPR and PFR had a high level of AUC (AUC = 0.943 and AUC = 0.912, respectively). CONCLUSIONS: The CPR and PFR are two promising novel inflammatory markers for assessing disease activity in RA patients.
Subject(s)
Arthritis, Rheumatoid , C-Reactive Protein/analysis , Fibrinogen/analysis , Prealbumin/analysis , Adult , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/physiopathology , Biomarkers/blood , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective StudiesABSTRACT
The level of need and costs of obtaining long-term care (LTC) during retired life require that planning for it is an integral part of retirement planning. In this paper, we divide retirement planning into two phases, pre-retirement and post-retirement. On the basis of four interrelated models for health evolution, wealth evolution, LTC insurance premium and coverage, and LTC cost structure, a framework for optimal LTC insurance purchase decisions in the pre-retirement phase is developed. Optimal decisions are obtained by developing a trade-off between post-retirement LTC costs and LTC insurance premiums and coverage. Two-way branching models are used to model stochastic health events and asset returns. The resulting optimization problem is formulated as a dynamic programming problem. We compare the optimal decision under two insurance purchase scenarios: one assumes that insurance is purchased for good and other assumes it may be purchased, relinquished and re-purchased. Sensitivity analysis is performed for the retirement age.