Role of surface charge on the interaction between carbon nanodots and human serum albumin.

Carbon nanodots (Cdots) have aroused widespread concerns in the field of biomedical applications. In order to achieve better implications of behavior of Cdots in the biological environment, an array of spectroscopic, electrochemical and calorimetric techniques were performed to study the interaction of Cdots possessing different charges with human serum albumin (HSA) in physiological condition. Two polymer, polyethylene glycol (PEG) and polyetherimide (PEI), were applied to passivate the bare Cdots to achieve the Cdots with different surface charge, namely negatively charged PEG Cdots and positively charged PEI Cdots. The fluorescence of HSA was obviously quenched by both Cdots in a charge-independent behavior through a dynamic collision mechanism. Moreover, the association affinity of PEG Cdots or PEI Cdots bound to HSA was very close to each other. In addition, PEG Cdots with diverse content exhibited little effects on the secondary structure of HSA while only high content of PEI Cdots induced obvious conformation perturbation of HSA. The electrostatic forces dominate the association between HSA and PEI Cdots while the association of PEG Cdots to HSA is initiated by hydrophobic and van der Waals forces. Furthermore, the results of isothermal titration calorimetry revealed that both the interaction was driven by favorable entropy and enthalpy, which confirmed that these association processes are thermodynamically spontaneous. Finally, the sites marker competitive experiment showed that the association sites of Cdots with HSA exhibit a charge dependent manner, namely PEG Cdots effectively occupy the site I of HSA while the association sites of PEI Cdots are mainly located in site II.

Comprehensive study of the interaction between a potential antiprion cationic porphyrin and human prion protein at different pH by using multiple spectroscopic methods.

Cationic porphyrins are potential antiprion drugs; however, the action mechanisms remain poorly understood. Herein, the interaction between a cationic porphyrin and recombinant human prion protein (rPrP(C)) was comprehensively studied by using surface plasmon resonance (SPR), fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. The experimental results showed that the interaction between the cationic porphyrin and rPrP(C) was pH dependent. The equilibrium association constants obtained from SPR spectroscopy were 4.12 × 10(3) M(-1) at pH 4.0, 1.74 × 10(5) M(-1) at pH 6.0, and 5.98 × 10(5) M(-1) at pH 7.0. The binding constants at 298 K obtained from the fluorescence quenching method were 7.286 × 10(4) M(-1) at pH 4.0 and 1.457 × 10(5) M(-1) at pH 6.0. The thermodynamic parameters such as enthalpy change, entropy change, and free energy change were calculated, and the results indicated hydrogen bonds and van der Waals interactions played a major role in the binding reaction. The RLS experiment was performed to study the influence of porphyrin on the rPrP(C) aggregation at different pH values. The CD experiments were conducted to investigate the effects of porphyrin on the secondary structure and thermal stability of rPrP(C). Finally, the comparison of SPR measurement and fluorescence quenching measurement was discussed.

Reversal alterations of amplitude of low-frequency fluctuations in early and late onset, first-episode, drug-naive depression.

BACKGROUND: It is unclear how patients with early onset depression (EOD) and late onset depression (LOD) differ at the neural level. Using amplitude of low-frequency fluctuations (ALFF) approach, we are to test the hypothesis of the different abnormal neural activities between patients with EOD and LOD. METHODS: Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS were enrolled in the study. ALFF approach was employed to analyze the images. RESULTS: ANOVA analysis revealed widespread differences in ALFF values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ALFF in bilateral precuneus, superior medial frontal gyrus and superior frontal gyrus, and lower ALFF in left brainstem and left superior temporal gyrus. Compared to young HS, lower ALFF in left superior/inferior temporal gyrus, left lingual gyrus and right middle occipital gyrus and higher ALFF in left medial frontal gyrus and bilateral superior frontal gyrus were seen in the EOD group; in contrast, in the LOD group, lower ALFF in bilateral superior frontal gyrus and higher ALFF in left superior temporal gyrus were observed. Further ROC analysis suggested that the mean ALFF values in the bilateral superior frontal gyrus and left superior temporal gyrus could serve as markers to separate patients with EOD from individuals with LOD. CONCLUSIONS: Patients with EOD and LOD exhibit reversal pattern of abnormal ALFF in bilateral superior frontal gyrus and left superior temporal gyrus.

Adhesion of quantum dots-induced membrane damage of Escherichia coli.

The toxicity of CdTe QDs modified with three different ligands, namely mercaptopropionic acid (MPA), N-acetyl-L-cysteine (NAC), and glutathione (GSH), were investigated via microcalorimetric, spectroscopic, and microscopic methods. The three ligand-modified QDs have nearly identical hydrodynamic size. The results of the calorimetric experiments and optical density measurements indicate that the QDs inhibited the growth of Gram-negative Escherichia coli. The toxicity order of the three QDs is MPA-CdTe QDs>GSH-CdTe QDs>NAC-CdTe QDs. The inhibitory effects of the QDs, cadmium chloride (CdCl(2)), MPA, and the CdCl(2) and MPA mixture on E. coli growth indicate that the toxicity mechanism of QDs may be related to their bacterial adhesion. When dispersed in the cell suspensions, QDs tend to have their high surface energy reduced through adsorption to the bacterial surface, as confirmed by transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy results. Furthermore, the effect of QDs on the membrane fluidity and permeability was investigated. GSH-CdTe QDs have a greater effect on the membrane function of E. coli than those of MPA-CdTe and NAC-CdTe QDs. This result may be attributed to the stronger lipophilicity of GSH compared with those of MPA and NAC.

Early and late onset, first-episode, treatment-naive depression: same clinical symptoms, different regional neural activities.

BACKGROUND: Patients with early onset depression (EOD) and late onset depression (LOD) have distinctive risk factors and clinical pictures. Using regional homogeneity (ReHo) approach, we were to test the hypothesis of the different abnormal neural activity between patients with EOD or LOD. METHODS: Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS participated in the study. ReHo approach was employed to analyze the scans. RESULTS: ANOVA analysis revealed widespread differences in ReHo values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ReHo in right precuneus (PCu) and bilateral superior frontal gyrus, and lower ReHo in left superior temporal gyrus. Compared to young HS, lower ReHo in left parahippocampal gyrus and higher ReHo in left fusiform gyrus and bilateral superior frontal gyrus were seen in EOD group; in contrast, in LOD group, lower ReHo in right PCu and higher ReHo in left superior temporal gyrus and left Crus I of the cerebellum were observed. Further ROC analysis suggested that the mean ReHo values in right PCu and bilateral superior frontal gyrus could serve as markers to identify patients with EOD from individuals with LOD. LIMITATION: The large age gap may limit the translational value of our findings. CONCLUSIONS: Patients with EOD and those with LOD have abnormal neural activities in different brain regions, although the two groups share the same symptoms.

Altered white matter integrity in young adults with first-episode, treatment-naive, and treatment-responsive depression.

Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.

Altered white matter integrity of forebrain in treatment-resistant depression: a diffusion tensor imaging study with tract-based spatial statistics.

BACKGROUND: The association between alterations of the white matter (WM) integrity in brain regions and mood dysregulation has been reported in major depressive disorder (MDD). However, there has never been a neuroimaging study in patients who have treatment-resistant depression (TRD) and are in a current treatment-resistant state. In the present study, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) method to investigate the WM integrity of different brain regions in patients who had TRD and were in a current treatment-resistant state. METHODS: Twenty-three patients with TRD and Hamilton Rating Scale total score of ≥18 and 19 healthy controls matched with age, gender, and education level to patients were scanned with DTI. Thirty 4 mm thick, no gap, contiguous axial slices were acquired and fractional anisotropy (FA) images were generated for each participant. An automated TBSS approach was used to analyze the data. RESULTS: Voxel-wise statistics revealed that patients with TRD had lower FA values in the right anterior limb of internal capsule, the body of corpus callosum, and bilateral external capsule compared to healthy subjects. Patients with TRD did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain region and patients' demographics and the severity of illness. CONCLUSIONS: Our findings suggest the abnormalities of the WM integrity of neuronal tracts connecting cortical and subcortical nuclei and two brain hemispheres may play a key role in the pathogenesis of TRD.

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: a resting-state fMRI study.

BACKGROUND: Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients. METHODS: Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS: There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit. CONCLUSIONS: The affected brain circuits of TRD patients might be partly different from those of TSD patients.

Abnormal neural activities in first-episode, treatment-naïve, short-illness-duration, and treatment-response patients with major depressive disorder: a resting-state fMRI study.

BACKGROUND: Abnormality of limbic-cortical networks was postulated in depression. Using a regional homogeneity (ReHo) approach, we explored the regional homogeneity (ReHo) of the brain regions in patients with first-episode, treatment-naïve, short-illness-duration, and treatment-response depression in resting state to test the abnormality hypothesis of limbic-cortical networks in major depressive disorder (MDD). METHODS: Seventeen patients with treatment-response MDD and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. CONCLUSIONS: Our findings suggested the abnormality of limbic-cortical networks in first-episode, treatment-naïve, short-illness-duration, and treatment-response MDD patients, and added an expanding literature to the abnormality hypothesis of limbic-cortical networks in MDD.

[The efficacy and safety of recombinant human insulin injection in the treatment of diabetic patients:a multicenter, randomized, controlled and open-labeled clinical trial].

OBJECTIVE: A multicenter, randomized, controlled and open-labeled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection (Yousilin R) and Novolin R in diabetic patients. METHODS: A total of 211 cases were randomized into two groups (1:1) treated with Yousilin R versus Novolin R for 12 weeks respectively. RESULTS: Compared with baseline, the levels of glycosylated hemoglobin A1c (HbA1c) at the end of 12 weeks treatment decreased from 10.77% to 7.72%(P < 0.05) in Yousilin R group and from 10.33% to 7.62% (P < 0.05) in Novolin R group, 2-hour postprandial plasma glucose (2hPG) decreased from 15.49 mmol/L to 9.72 mmol/L (P < 0.05) in Yousilin R group and from 15.33 mmol/L to 10.07 mmol/L (P < 0.05) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10.90 mmol/L to 7.31 mmol/L (P < 0.05) in Yousilin R group and from 10.22 mmol/L to 7.21 mmol/L (P < 0.05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group (P > 0.05). Furthermore, hypoglycemic events (26.42% vs 30.48%), other adverse events (13.21% vs 16.19%), and serious adverse events (1.89% vs 1.90%) were comparable between Yousilin R and Novolin R groups (P > 0.05). CONCLUSIONS: Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.

Interaction between a cationic porphyrin and bovine serum albumin studied by surface plasmon resonance, fluorescence spectroscopy and cyclic voltammetry.

The interaction between a cationic porphyrin and bovine serum albumin (BSA) was studied by using surface plasmon resonance (SPR) spectroscopy, which was combined with fluorescence quenching method and cyclic voltammetric method to confirm the binding kinetic results. In this paper, the SPR method used to study the drug-protein interaction was described in detail. The association rate constant, dissociation rate constant and the equilibrium association constant of porphyrin binding to BSA obtained from this method were 1067 ± 18.23 M(-1) s(-1), 0.01644 ± 0.00012 s(-1), and 6.49 × 10(4) M(-1), respectively. The equilibrium association constants obtained from the fluorescence quenching method and the cyclic voltammetric method were 1.102 × 10(5) M(-1) and 1.21 × 10(5) M(-1), respectively.