Search

Bullying victimization has been linked to an elevated risk of both internalizing and externalizing problems, yet the mechanisms underlying these associations, especially from the perspective of naturally occurring informal cliques, are not well understood. Based on two contrasting hypotheses from the healthy context paradox and the peer contagion hypothesis, the current 2-year longitudinal study (a) investigated the interaction effects of individual victimization (i.e., physical, verbal, and relational forms) and clique victimization norms on their reactive-proactive aggression and (b) examined whether they were distinct to these effects on depressive symptoms. Both self-reported and peer-nominated surveys were administrated to 691 junior high school students (55.6% boys; M age = 12.74, SD = 0.43 years) who were identified from 153 cliques (M size = 5.08, SD = 1.89) using a social cognitive map, at two time points 2 years apart. Multilevel modeling indicated that both physical and relational victims (except verbal victims) at baseline committed more reactive forms of aggression (not proactive forms) in cliques with lower victimization norms 2 years later. Similarly, physical victims in lower-victimization cliques reported more depressive symptoms 2 years later. Additionally, these significant results were found in self-reported forms of victimization, but not peer-nominated forms. These findings confirm the healthy context paradox in both individual internalizing and externalizing problems in clique contexts, and elaborate this paradox on different forms of victimization, which provide a more nuanced understanding and have important implications in the field of anti-bullying interventions. [ABSTRACT FROM AUTHOR]

Aims Glucagon like-peptide-1 (GLP-1)-based drugs have been proposed as mono- or combined therapy for type 2 diabetes mellitus. Thus we characterized a novel antibody fusion protein engineered by linking the human GLP-1 derivative to a humanized GLP-1 receptor (GLP-1R) antibody via a peptide linker. Materials and methods Glutazumab was characterized by receptor binding and reporter activation assays, and its specificity was investigated with the aid of the cognate receptor antagonist exendin (9-39) and antibody Ab1. Pharmacokinetics was evaluated in Sprague-Dawley (SD) rats and cynomolgus monkeys, and pharmacodynamics was assessed in normal ICR and spontaneous type 2 diabetic KKAy mice. Hypoglycemic effects were evaluated after acute administration and glucose metabolism and β-cell function were assessed with repeated administrations. Dulaglutide was a positive control in all experiments. Results Glutazumab significantly bound and activated GLP-1R, but the receptor antagonist exendin (9-39) did not inhibit the activation except when combined with Ab1. Single injection of glutazumab reduced the blood glucose in ICR mice and KKAy mice, and the half-lives in SD rats and cynomolgus monkeys were 18 h and 33.6 h. Repeated injections of glutazumab controlled glycemic fluctuations and improved β-cell function in KKAy mice. Conclusions As a novel GLP-1R agonist, glutazumab may be a potential treatment for T2DM. [ABSTRACT FROM AUTHOR]

Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KK Ay mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KK Ay mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF- κ B p65), inhibitor of NF- κ B (I κ B α ), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KK Ay mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Attachment security refers to individuals' ability of viewing attachment figures as a secure base for exploration and a safe haven in times of need. Two studies examined whether dispositional and temporarily primed attachment security could improve response inhibition following ego-depletion among Chinese college students. We manipulated ego-depletion with a stressful task — preparing a three-minute speech within 5 min and assessed response inhibition with Stroop color naming tasks. Study 1 randomly assigned participants to the ego-depletion and control groups and assessed dispositional attachment anxiety and avoidance. Results showed that participants in the ego-depletion group reacted slower to incongruent trials than their counterparts. Whereas attachment avoidance predicted faster reactions to incongruent trials in the ego-depletion group, such relationship was absent in the control group. Study 2 randomly asked participants to visualize a responsive and available other (attachment security priming condition) or an acquaintance (acquaintance priming condition). Results indicated that following ego-depletion, attachment avoidance again predicted faster reactions to incongruent trials, and participants from the attachment security priming condition also reacted faster to incongruent trials than those from the acquaintance priming condition. Findings offer additional support for social defense theory and the broaden-and-build cycle of attachment security. [ABSTRACT FROM AUTHOR]

A cross-sectional study of a large, middle-school student sample ( N = 966) was presented in this paper aiming to examine how parental behavior and self-control influence Internet addiction (IA) among Chinese adolescents. Fifty-one adolescents (the top 5% of IA score distribution) were categorized as at high risk. Males were more likely addicted to Internet than females. MANOVA demonstrated that, compared with non-IA group, adolescents with IA revealed lower mean score for parental positive support behavior and higher for parental negative control behavior and had lower capacity of self-control. SEM analyses revealed that low capacity of self-control had a negative correlation with parents’ positive support and a positive correlation with negative control. More importantly, Internet addiction was explained negatively by parents’ positive support and positively by parents’ negative control and individual low capacity of self-control. Further mediating analyses indicated that self-control accounted for an indirect role between parental behavior and adolescents’ Internet addiction. The findings of the present study are of significance in investigating adolescents’ problem behaviors and very helpful to provide educational advice for intervening in these behaviors. Moreover, the present finding’s potential relevance to Confucian styles of filial parenting was discussed. [ABSTRACT FROM AUTHOR]

Highlights: [•] A conformational mechanism model for online communication and subjective well-being is proposed. [•] The mechanism operating by shyness and social self-efficacy. [•] The influence of social self-efficacy varies between shy and no-shy participants. [•] The mechanism is moderated by gender. [Copyright &y& Elsevier]

Abstract: Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30ng/mL and 20ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors. [Copyright &y& Elsevier]

Berberine is effective for type 2 diabetes mellitus (T2DM), but has limited use in clinic. This study aims to evaluate the effect of berberine combined with stachyose on glycolipid metabolism and gut microbiota and to explore the underlying mechanisms in diabetic rats. Zucker diabetic fatty (ZDF) rats were orally administered berberine, stachyose and berberine combined with stachyose once daily for 69 days. The oral glucose tolerance and levels of blood glucose, insulin, triglyceride and total cholesterol were determined. The gut microbial profile, colonic miRNA and gene expression were assayed using Illumina sequencing. The quantitative polymerase chain reaction was used to verify the expression of differentially expressed miRNAs and genes. Repeated treatments with berberine alone and combined with stachyose significantly reduced the blood glucose, improved the impaired glucose tolerance, and increased the abundance of beneficial Akkermansiaceae , decreased that of pathogenic Enterobacteriaceae in ZDF rats. Furthermore, combined treatment remarkably decreased the abundances of Desulfovibrionaceae and Proteobacteria in comparison to berberine. Combined treatment evidently decreased the expression of intestinal early growth response protein 1 (Egr1) and heparin-binding EGF-like growth factor (Hbegf), and significantly increased the expression of miR-10a-5p, but berberine alone not. Berberine combined with stachyose significantly improved glucose metabolism and reshaped gut microbiota in ZDF rats, especially decreased the abundance of pathogenic Desulfovibrionaceae and Proteobacteria compared to berberine alone, providing a novel strategy for treating T2DM. The underlying mechanisms may be associated with regulating the expression of intestinal Egr1 , Hbegf and miR-10a-5p, but remains further elucidation. Repeated treatments with berberine in combination with stachyose significantly improves glycometabolism and reshaped gut microbiota profile in diabetic ZDF rats, and this is partly mediated by regulating colonic miR-10a-5p, Erg1 and Hbegf expression. [Display omitted] • Berberine plus stachyose improves glycometabolism, shapes microbiota in diabetic rat. • Berberine plus stachyose increases colonic miR-10a-5p expression in diabetic rat. • Berberine plus stachyose decreases colonic Egr1 and Hbegf expression in diabetic rat. • Changes of miR-10a-5p, Egr1 and Hbegf explain effects of berberine plus stachyose. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are implicated in the occurrence and progression of diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple diaryl diselenide with anti-hyperglycemic, anti-inflammatory, and antioxidant activities. However, the effects of DPDS on DN are still unclear to date. Herein, we aimed to explore whether DPDS could improve renal dysfunction in streptozotocin (STZ)-induced diabetic rats and its underlying mechanisms. STZ-induced DN rats were administered with DPDS (5 or 15 mg/kg) or metformin (200 mg/kg) once daily by intragastric gavage for 12 weeks. DPDS supplementation significantly improved hyperglycemia, glucose intolerance, dyslipidemia, and the renal pathological abnormalities, concurrent with significantly reduced serum levels of creatinine, urea nitrogen, urine volume, and urinary levels of micro-albumin, β2-microglobulin and N-acetyl-glucosaminidase activities. Moreover, DPDS effectively promoted the activities of antioxidant enzymes, and reduced the levels of MDA and pro-inflammatory factors in serum and the kidney. Furthermore, DPDS supplementation activated the renal Nrf2/Keap1 signaling pathway, but attenuated the high phosphorylation levels of NFκB, JNK, p38 and ERK1/2. Altogether, the current study indicated for the first time that DPDS ameliorated STZ-induced renal dysfunction in rats, and its mechanism of action may be attributable to suppressing oxidative stress via activating the renal Nrf2/Keap1 signaling pathway and mitigating inflammation by suppressing the renal NFκB/MAPK signaling pathways, suggesting a potential therapeutic approach for DN. [Display omitted] • Diphenyl diselenide (DPDS) ameliorated STZ-induced diabetic nephropathy in rats. • DPDS ameliorated systemic and renal oxidative stress in diabetic rats. • DPDS ameliorated systemic and renal inflammation in diabetic rats. • DPDS activated the renal Nrf2/Keap1 signaling pathway in diabetic rats. • DPDS suppressed the renal NFκB and MAPK signaling pathways in diabetic rats. [ABSTRACT FROM AUTHOR]

The present article explored the effect of attachment on grandiose narcissism via perceived parental trust through a cross-sectional investigation using moderated mediation models. The Experiences in Close Relationships Inventory, Perceived Parental Trust Questionnaire, and Narcissistic Admiration and Rivalry Questionnaire were administered to 2260 middle school students of China (1094 seventh and 1166 tenth grade students). Results indicated that attachment avoidance and attachment anxiety exert distinct influence on narcissism's self-enhancement (i.e., admiration) directly, while both attachment anxiety and avoidance foster self-protection (i.e., rivalry) directly. Furthermore, the strength of the indirect effect of one attachment dimension on narcissism via perceived parental trust is stronger when the other is lower, or when the grade is younger. [ABSTRACT FROM AUTHOR]

Family violence as an inducing factor of depressive symptoms has been confirmed in previous studies. However, the mechanisms underlying this association are not well understood, particularly in Chinese adolescents. Guided by the social-ecological diathesis-stress model, this three-wave longitudinal study aimed to examine the effects of an individual's cognitive vulnerabilities (rejection-sensitivity anxiety and negative cognitive error) and positive societal contexts (peer support) on the link between family violence and depressive symptoms in Chinese society. A total of 859 Chinese adolescents (44.35 % female; M age = 12.73, SD = 0.43 at baseline) completed self-reporting surveys that assessed variables associated with study and peer-nominated peer support. The results showed that family violence increased the incidence of depressive symptoms in adolescents after two years, resulting in rejection-sensitivity anxiety and negative cognitive error. Surprisingly, higher self-reported peer support, although not peer-nominated support, exacerbated rather than mitigated this indirect effect, supporting the reverse stress-buffering model and extending the healthy context paradox. Most of the measures were based on participants' self-reports. These results emphasize the importance of individual cognition and societal contexts in adolescents with traumatic experiences and provide empirical evidence for the intervention and clinical treatment of depressive symptoms. • The experience of family violence at baseline significantly predicted adolescent depressive symptoms two years later. • Family violence increased adolescent depressive symptoms 2 years later via cognitive vulnerabilities. • Higher self-reported peer support exacerbated this indirect effect between family violence and depressive symptoms. [ABSTRACT FROM AUTHOR]

This longitudinal cross-lagged research attempts to examine the directions of relations between Internet addiction and both internalizing and externalizing problems, with attention to the potential moderating effects of peer relationships and gender. 897 Chinese junior middle school students (56.97% boys, M age = 12.73 years, SD = 0.42) completed self-reported Internet addiction, depressive symptoms, and peer-nominated aggressive behavior at two time points, one year apart, as well as self-reported friend support/conflict and positive/delinquent peers at baseline. Cross-lagged panel analyses revealed that adolescents' Internet addiction would elevate both depressive symptoms and aggressive behavior over time, rather than vice versa. Furthermore, friend conflict (rather than support) moderated these unidirectional relationships that when individuals perceived lower friend conflict, these links were no longer significant. Moreover, similar results were found for adolescents who possessed more positive peers or fewer delinquent peers. In addition, gender differences were found that addicted boys were more vulnerable to aggressive behavior, while addicted girls were more vulnerable to depressive symptoms. These findings suggest that establishing and maintaining good peer social networks would help adolescents keep away from the harmful impacts of Internet overuse on maladjustment. • Adolescents' Internet addiction would elevate both depressive symptoms and aggressive behavior over time, but not vice versa. • Peer relationships played salutary roles in the effects of Internet addiction on internalizing and externalizing problems. • Higher friend conflict would make addicted adolescents more vulnerable to internalizing and externalizing problems. • Affiliation with more positive peers or less delinquent peers protected addicted adolescents from aggressive behavior. • Due to overindulge in the Internet, boys were prone to aggression, whereas girls were prone to depression. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients. Oxidative stress (OS) plays a key role in the pathogenesis of DPN; thus, antioxidant therapy is considered a promising strategy for treating DPN. Diphenyl diselenide (DPDs) is an organic selenium compound with antioxidant pharmacological activities. This study aimed to evaluate its preventive and therapeutic effects on DPN in rats with streptozotocin (STZ)-induced diabetes and explore the underlying mechanisms. In vitro, RSC96 cells were exposed to high glucose (100 mM) and then treated with different concentrations of DPDs (1, 10, 25 and 50 μM). Notably, DPDs markedly suppressed high glucose-induced cytotoxicity and oxidative stress in Schwann cells by decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Furthermore, the DPDs treatment effectively activated Nrf2 signaling and inhibited Keap1 expression. An in vivo DPN model was established in Sprague-Dawley (SD) rats injected with STZ (60 mg·kg−1, ip) and orally administered either different doses of DPDs (5 and 15 mg· kg−1· d−1) for 12 weeks or alpha lipoic acid (ALA, 100 mg kg−1·d−1) as a positive control. The administration of DPDs significantly increased the motor nerve conduction velocity (MNCV), improved thermal and mechanical hyperalgesia and the sciatic nerve morphology, and ameliorated oxidative stress in the serum and the sciatic nerve of rats with DPN. Mechanistically, DPDs reduced the level of Keap1 and stimulated Nrf2 signaling in the sciatic nerve. Taken together, the results of this study indicate that DPDs ameliorates experimental DPN as an antioxidant by activating the Nrf2/Keap1 signaling pathway. DPDs may represent a new alternative treatment for DPN. [ABSTRACT FROM AUTHOR]

The present study seeks to examine the effect of attachment orientations on dispositional gratitude and whether it would be mediated by self-esteem and perceived social support. Nine-hundred-and-twenty-eight Chinese college students completed the Self-esteem Scale (SES), the Multidimensional Perceived Social Support Scale (MPSSS), the Experiences in Close Relationships Inventory (ECR), and the Gratitude Resentment and Appreciation Test (GRAT). It was revealed that both attachment avoidance and attachment anxiety were negatively associated with dispositional gratitude. Mediational analyses showed that attachment avoidance was indirectly related to dispositional gratitude through perceived social support and self-esteem, whereas attachment anxiety exerted effect on dispositional gratitude both directly and indirectly through self-esteem. These findings highlight the importance of attachment security for cultivating virtues such as dispositional gratitude and contribute to a more complete understanding of self- and other-representations. [ABSTRACT FROM AUTHOR]

This cross-sectional study investigates how perceived support and relational conflict mediate the associations of attachment orientations with depressive symptoms among 367 (153 Chinese, 214 American) dating individuals. Results revealed a pan-cultural association of attachment anxiety with depressive symptoms mediated though relational conflict. Attachment avoidance was more strongly related to depressive symptoms through relational conflict in the Chinese sample than in the U.S. sample. Furthermore, attachment anxiety was related to perceived support across both cultural samples, while attachment avoidance was more strongly related to perceived support in the Chinese sample than in the U.S. sample. Findings are discussed in terms of the cultural logics governing interpersonal relationships across cultures. [ABSTRACT FROM AUTHOR]