Developmental Pattern of Diurnal Cortisol Rhythm and Sex-Specific Associations With Psychopathological Symptoms During Pubertal Transition.

OBJECTIVE: This study aimed to examine the developmental pattern of diurnal cortisol rhythm during pubertal transition and its prospective association with psychopathological symptoms. METHODS: A cohort of 1158 children consisting of 608 boys and 550 girls aged 7 to 9 years (mean [standard deviation] age = 8.04 [0.61] years) were recruited in the Anhui Province of China in 2015 (wave 1). A single awakening sample was collected at baseline, and three additional samples were collected at one weekday in wave 2 to wave 4. Four indices of cortisol activity were evaluated and calculated across the day: awakening cortisol level, cortisol awakening response, the area under the curve with respect to ground (AUC), and the diurnal cortisol slope. In each wave, pubertal development was assessed by testicular size in boys and Tanner scales in girls. Psychopathological symptoms were ascertained in waves 2 to 4. RESULTS: Multilevel mixed models revealed no significant pubertal changes in diurnal cortisol activity in girls. In boys, awakening cortisol (ß = -0.005, p = .004) and total cortisol output (lnAUC, ß = -0.005, p = .040) significantly decreased across pubertal transition. Higher awakening cortisol and total cortisol output (lnAUC) were associated with higher scores on internalizing symptoms in girls (ß = 0.82, p < .001; ß = 0.62, p = .012) and externalizing symptoms in boys (ß = 0.73, p = .001; ß = 0.55, p = .019) during the 3-year follow-up. In contrast, no associations were found between cortisol awakening response and diurnal cortisol slope with psychopathological symptom scores in boys or girls. CONCLUSIONS: Development of diurnal cortisol activity during pubertal transition occurs in a sex-specific manner. Awakening cortisol level and daily total cortisol output may serve as markers for psychopathology during pubertal transition.

Pubertal recalibration of cortisol reactivity following early life parent-child separation.

BACKGROUND: The hypothalamic-pituitary-adrenocortical (HPA) axis had been proved to calibrate to early-life adversity and puberty may reverse the calibration. This study examines the consequences of prolonged parent-child separation on HPA axis reactivity and the pubertal recalibration hypothesis. METHODS: Totally of 144 participants aged 8.75 to 15.25 (mean age 12.50 years, SD: 1.32) were enrolled from rural areas of Chizhou city, Anhui Province of China in 2019. Data on parent-child separation was collected from parents. Self-reported Peterson Pubertal Development Scale was used to assess pubertal maturation and HPA axis stress reactivity was measured using the Trier Social Stress Test for Children. RESULTS: For children at early stage of puberty, childhood parent-child separation experiences were associated with blunted HPA axis reactivity (B = -1.888, p = 0.034); while for those at later stage of puberty, HPA axis reactivity was similar between children experienced early childhood separation and those without separation (AUCi: B = -0.426, p = 0.878). In contrast, for children experienced persistent parent-child separation, blunted HPA axis reactivity was observed (all p < 0.05). LIMITATIONS: Due to the cross-sectional nature of this study, conclusions about causality remain speculative. CONCLUSIONS: The effect of parent-child separation on dysregulation of HPA axis acts in a time-dependent manner. This finding provides support for the pubertal recalibration hypothesis suggesting that a focus of improving environment in adolescence would help those individuals reared initially in non-supportive conditions.

PEGylated titanate nanosheets: hydrophilic monolayers with a superior capacity for the selective isolation of immunoglobulin G.

A novel organic-inorganic hybrid was prepared by anchoring (3-aminopropyl)triethoxysilane (APTES) on the surface of monolayer titanate nanosheets and subsequent modification with hydrophilic polyethylene glycol (PEG). The PEGylated hydrophilic monolayer titanate nanosheets were abbreviated as PEG-APTES-TiNSs, and they exhibit a lateral dimension of dozens of nanometers and a thickness of ca. 1.9 nm. PEGylation of the titanate nanosheets significantly improved their selectivity toward the adsorption of glycoproteins through strong hydrophilic interaction, providing an adsorption capacity of 2540.9 mg g-1 for immunoglobulin G (IgG). The retained IgG is readily collected at a recovery rate of 83.4% with 0.5% (m/v) ammonium hydroxide (NH4OH) as the stripping reagent. PEG-APTES-TiNSs are applied for the selective adsorption of IgG from human serum, which is further confirmed by SDS-PAGE assay.

CS/PAA@TPGS/PLGA nanoparticles with intracellular pH-sensitive sequential release for delivering drug to the nucleus of MDR cells.

Development of novel nano-drug delivery systems (NDDS) that can transport anticancer drugs into cell nuclei is still a highly desirable strategy for reversing multi-drug resistance (MDR) in cancer therapy. Herein, we designed and prepared a novel NDDS, designated S@L NPs, in which several smaller nanoparticles are contained within a larger nanoparticle. Our S@L NPs (CS/PAA/VP-16@TPGS/PLGA NPs) possess a structure in which smaller nanoparticles (Chitosan-Poly(acrylic acid) nanoparticles, CS/PAA NPs) containing the drug etoposide (VP-16) are loaded within a larger nanoparticle (Vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles, TPGS/PLGA NPs). The system utilizes intracellular pH gradients to achieve pH-sensitive sequential release within different intracellular domains of MDR cells. S@L NPs could be triggered to degrade and release CS/PAA/VP-16 NPs in the acid environment of the cytosol, endosomes or lysosomes, and CS/PAA/VP-16 NPs were capable of entering the nucleus through nucleopores. It is significant that CS/PAA/VP-16 NPs exhibit disaggregation in the alkaline environment of the nucleus and thereby release the contained anticancer drug. Further mechanistic studies showed that CS/PAA/VP-16 NPs escaped retention and degradation within lysosomes and protected the drug from P-glycoprotein-induced efflux. Simultaneously, S@L NPs enhanced the anticancer effect of the loaded drug by inducing autophagy and apoptosis of MDR cells. This novel NDDS may provide a promising platform for nuclear drug delivery for reversing MDR.

Polyethyleneimine-iron phosphate nanocomposite as a promising adsorbent for the isolation of DNA.

A polyethyleneimine (PEI)-iron phosphate (FePO4) nanocomposite is prepared by immobilization of PEI onto the surface of FePO4 nanoparticles via electrostatic interaction. The obtained PEI-FePO4 nanocomposites are spherical with a size centered in ca. 100 nm. They provide a novel adsorbent for the solid-phase extraction of DNA from complex sample matrices. At pH 4, 50 µg mL(-1) of DNA (salmon sperm DNA sodium salt) in 1.0 mL aqueous solution are quantitatively adsorbed (100%) by 2mg of the PEI-FePO4 nanocomposites, and meanwhile the coexisting albumin at a same concentration level is not retained, demonstrating the favorable selectivity of the nanocomposites to DNA against proteins. The adsorption behaviors of DNA onto the PEI-FePO4 nanocomposites fit Langmuir model, corresponding to an adsorption capacity of 61.88 mg g(-1). The adsorbed DNA could be readily recovered by using a 0.04 mol L(-1) Britton-Robinson (BR) buffer at pH 10, resulting in a recovery of 85%. The nanocomposites have been further used for the isolation of DNA from a series of real sample matrices, including synthetic λ-DNA sample, human whole blood and Escherichia coli cell lysate. The extraction efficiency and the purity of the recovered DNA are at least comparable to those achieved by using the reported sorbent materials or commercial kits. In addition, the DNAs isolated from human whole blood and E. coli cell lysate are of high quality, which have been further demonstrated by using them as templates for successful PCR amplifications.

[Cytotoxicity of a novel endodontic treatment material iRoot BP Plus to human gingival fibroblasts].

PURPOSE: To compare the cytotoxicity of a novel endodontic treatment material iRoot BP Plus and mineral trioxide aggregate (MTA) to human gingival fibroblasts in vitro. METHODS: Cultured human gingival fibroblasts were exposed to multiple concentrations of material elutes (no dilution, 1:2 dilution, and 1:5 dilution). The test material samples were immersed and incubated in the culture medium for 1, 3 or 7 days at 37 degrees centigrade. The proliferation rate was evaluated using methylthiazol tetrazolium (MTT) assay. Cell relative growth rates were presented as x±s. The data was statistically analyzed by factorial design ANOVA using SPSS 20.0 software package. RESULTS: Cell relative growth rates of the eluates of iRoot BP Plus and MTA in different concentrations ranged from 77.31% to 113.82%. The cytotoxicity grade of both materials was 0 or 1 (no cytotoxicity). There was no significant difference in the relative growth rate in different concentrations of iRoot BP plus and MTA eluates under different elution times (F(concentration×time×material)=1.393, P=0.256). CONCLUSIONS: Both iRoot BP Plus and MTA exhibit minimal level of cytotoxicity.

Histologic comparison between platelet-rich plasma and blood clot in regenerative endodontic treatment: an animal study.

INTRODUCTION: In regenerative endodontic treatment (RET) for immature permanent tooth, better treatment results could be obtained by applying platelet-rich plasma (PRP) as the scaffold rather than the blood clot. The goal of this study was to compare the histologic differences between using PRP and blood clot in RET. METHODS: Three 6-month-old beagles each carrying 9 premolars with double root canals were randomly assigned to the PRP group, blood clot group, or negative control group. All experimental teeth suffered apical periodontitis, and RET was performed. In the blood clot group, bleeding was induced from the periapical tissues to fill the canal space. In the PRP group, autologous PRP was injected into each root canal. The animals were sacrificed 3 months later. Histologic sections were stained with hematoxylin-eosin. Statistical analysis was performed by the Fisher exact test, with the significance set at 0.05. RESULTS: With the ingrowth of cellular cementumlike tissues, the canal wall was thickened, and the apical apex was closed in both the PRP and blood clot groups. Cementocytelike cells were present in the newly formed tissues. Meanwhile, no statistical difference was found in both experimental groups for the average percentage of apical closure, new tissue formation, and pulplike tissue formation. Noticeably, a large number of inflammatory cells were present in some root canals in both groups although the postoperative radiograph revealed the disappearance of periapical radiolucency. CONCLUSIONS: PRP application could be an option for clinical cases in which little or no bleeding were found when irritating the apical tissue during RET.