Differential plasma proteome profiles of mild versus severe β-thalassemia/Hb E

The severity of thalassemia is currently classified based on clinical manifestations and multiple tests. In the present study, we performed a plasma proteome analysis to identify differentially expressed proteins compared between normal subjects and patients with mild and severe forms of β-thalassemia/hemoglobin E (Hb E). Plasma samples were collected from patients with mild (n?=?8) and severe (n?=?12) forms as well as healthy normal individuals (n?=?12). Clinical chemistry revealed that several parameters, i.e., hematological indices, oxidative stress markers, antioxidant enzymes, and erythropoietic activity, had significant differences among these three groups. After removal of seven major abundant proteins, the plasma proteome profiles were compared using two-dimensional gel electrophoresis. Spot matching, quantitative intensity analysis, and statistics revealed differential levels of 32 and 9 proteins when comparing normal vs. patients and mild vs. severe forms, respectively. These proteins were successfully identified by quadrupole time-of-flight mass spectrometry and/or tandem mass spectrometry. The decreased level of ADP-ribosylation factor guanine nucleotide-exchange factor 2 in β-thalassemia/Hb E patients compared to healthy individuals and the decreased level of endothelin-converting enzyme 2 in severe form compared to the mild form of the disease were validated by Western blot analysis. Our data provide a number of proteins that may lead to better understanding of the pathophysiology of thalassemia or for novel biomarkers which can be used to simply differentiate mild and severe forms of β-thalassemia/Hb E without any need for multiple tests.     

Proteomic analysis reveals plasma haptoglobin,interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy

BackgroundChildren with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need.MethodsEighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant.ResultsProteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1β was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1β may be involved with neuroinflammation.ConclusionsAlterations in plasma haptoglobin, IFN-γ, and IL-1β were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.     

Hyperthermia evaluation and drug/protein-controlled release using alternating magnetic field stimuli-responsive Mn–Zn ferrite composite particles

Drug delivery particles in which the release of biomolecules is triggered by a magnetic simulant have attracted much attention and may have great potential in the fields of cancer therapy and tissue regenerative medicine. In this study, we have prepared magnetic Mn–Zn ferrite ((Mn,Zn)Fe₂O₄) (MZF) nanoparticles coated with chitosan-g-N-isopropylacrylamide (Chi-g-NIPAAm) polymer (MZF@Chi-g-NIPAAm) to deliver the anticancer drug (Doxorubicin, DOX) and bioactive proteins (Bone morphogenic protein (BMP-2)-immobilized bovine serum albumin (BSA)) (P//MZF@Chi-g-NIPAAm) and be used as chemo-hyperthermia and vector delivering biomolecules. For these purposes, we first show that the as-prepared MZF@Chi-g-NIPAAm particles exhibit super paramagnetic behavior and under certain conditions, they can act as a heat source with a specific absorption rate (SAR) of 34.88 W g⁻¹. Under acidic conditions and in the presence of AMF, the fast release of DOX was seen at around 58.9% within 20 min. In vitro evaluations indicated that concurrent thermo-chemotherapy treatment by DOX-MZF@Chi-g-NIPAAm using AMF had a better antitumor effect, compared with those using either DOX or DOX-MZF@Chi-g-NIPAAm without AMF (89.02% of cells were killed as compared to 71.82% without AMF exposure). Up to 28.18% of the BSA (used as the model protein to determine the controlled release) is released from the P//MZF@Chi-g-NIPAAm particles under AMF exposure for 1 h (only 17.31% was released without AMF). These results indicated that MZF@Chi-g-NIPAAm particles could be used to achieve hyperthermia at a precise location, effectively enhancing the chemotherapy treatments, and have a promising future as drug or bioactive delivering molecules for cancer treatment and cartilage or bone regenerative applications.

Drug delivery particles in which the release of biomolecules is triggered by a magnetic simulant have attracted much attention and may have great potential in the fields of cancer therapy and tissue regenerative medicine.     

Endothelin ETB receptors contribute to sex differences in blood pressure elevation in angiotensin II hypertensive rats on a high‐salt diet

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