A follow-up study of peer relationships in autistic and non-autistic youths: Mediating effects from autistic, emotional and behavioral symptoms.

BACKGROUND: Little is known about how clinical features prospectively influence peer relationships in autistic populations. AIMS: This study investigated the clinical symptoms mediating the link between autism spectrum disorder (ASD) diagnosis and peer relationships at follow-up, i.e. the second time evaluation of this study. METHODS: The sample consisted of 366 autistic youths and 134 non-autistic comparisons. The autistic traits and emotional/behavioral problems were measured at baseline by Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL). The interactions and problems with peers were assessed by the Social Adjustment Inventory for Children and Adolescents (SAICA) at follow-up. RESULTS: Each subscore of SRS and CBCL showed significant mediation effects. Multiple mediation analyses showed atypical social communication, social awareness problems, and delinquent behaviors mediated the link from ASD to less active peer interactions after controlling for sex, age, and IQ. Moreover, atypical social communication, social-emotional problems, and attention difficulties predicted problems with peers. After considering these mediation effects, the diagnosis of ASD still demonstrated a significantly direct effect on peer relationships at follow-up. CONCLUSIONS AND IMPLICATIONS: Our findings support that social-related autistic features, attention problems, and delinquent behaviors mediated a link between ASD and peer relationships. These mediators are potential measures for improving interactions and decreasing difficulties with peers in the autistic population.

The sleep problems in individuals with Rett syndrome and their caregivers.

LAY ABSTRACT: Sleep problems are common and impactful among individuals with Rett syndrome (RTT) and their caregivers. We examined the sleep patterns of 29 RTT patients and their primary caregivers using various assessment tools. The study found that a majority of the patients experienced sleep disturbances, with younger patients showing more sleep difficulties. Caregivers also reported poor sleep quality. The findings emphasize the need to address sleep problems in RTT management, as improving sleep quality can positively impact the well-being of individuals with RTT and their caregivers.

Assessing Frontal Lobe Function on Verbal Fluency and Emotion Recall in Autism Spectrum Disorder by fNIRS.

This study applied the functional near-infrared spectroscopy (fNIRS) to investigate frontal activity in autism when performing verbal fluency test and emotion recall task. We recruited 32 autistic adults without intellectual disability and 30 typically-developing controls (TDC). Prefrontal hemodynamic changes were evaluated by fNIRS when the participants performed the verbal fluency test and emotion recall task. fNIRS signals in the prefrontal cortex were compared between autism and TDC. Compared to TDC, autistic adults showed comparable performance on the verbal fluency test but exhibited lower frontal activity on the vegetable category. In the verbal fluency test, left frontal activity in TDC significantly increased in the vegetable category (vs. fruit category). In the emotion recall task, left frontal activity increased significantly in TDC when recalling emotional (vs. neutral) events. This increase of left frontal activity on the more difficult works was not found in autism. Similarly, brain activities were related to test performance only in TDC but not in autism. In addition, more severe social deficits were associated with lower frontal activity when recalling emotional events, independent of autism diagnosis. Findings suggested reduced frontal activity in autism, as compared to TDC, when performing verbal fluency tests. The reduction of left frontal activation in verbal fluency test and emotion recall tasks might reflect on the social deficits of the individual. The fNIRS may potentially be applied in assessing frontal lobe function in autism and social deficits in general population. Trial registration number: NCT04010409.

Mothering and mother-child interactions in the unaffected siblings of autistic children.

AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children. METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting. RESULTS: Regardless of the child's age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics. INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child's behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.

Investigating the impact of probiotic on neurological outcomes in Rett syndrome: A randomized, double-blind, and placebo-controlled pilot study.

LAY ABSTRACT: Rett syndrome often involves gastrointestinal symptoms and gut microbiota imbalances. We conducted a study to explore the feasibility of probiotic Lactobacillus plantarum PS128 and the impact on neurological functions in Rett syndrome. The results of our investigation demonstrated that the supplementation of probiotic L. plantarum PS128 was feasible and well tolerated, with 100% retention rate and 0% withdrawal rate. In addition, there was only one participant who had loose stool after taking L. plantarum PS128. Further, there was a tendency to enhance overall cognitive developmental level, as assessed using Mullen Scales of Early Learning. In addition, it significantly improved dystonia, as assessed using the Burke-Fahn-Marsden Movement Scale, in comparison with the placebo group. This study provides a strong foundation for future research and clinical trials exploring the potential of L. plantarum PS128 probiotics as a complementary therapy for individuals with Rett syndrome.

The mediators for the link between autism and real-world executive functions in adolescence and young adulthood.

LAY ABSTRACT: Childhood factors that predict real-world executive function in autism spectrum disorder during the transition into adulthood are largely unknown. This study aimed to identify the predictors for the behavioral and cognitive aspects of real-world executive function in late adolescent and young adult autistic populations. We followed up 289 autistic youth (mean age 11.6 years) and 203 non-autistic controls (10.7 years) to their ages of 16.9 and 15.8, respectively. The Behavior Rating Inventory of Executive Function scale was used to measure the real-world executive function at late adolescence and young adulthood at follow-up. Potential predictors such as autistic symptoms, inattention or hyperactivity symptoms, peer relationship, emotional symptoms, and parenting styles were assessed in childhood at first enrollment. The results showed that childhood inattention, withdrawn behaviors, social communication difficulties, and child-reported emotion and inattention/hyperactivity may predict real-world lower executive function in late adolescence and young adults with autism. When separating executive function into behavioral and cognitive aspects, we found that oppositional behaviors and peer problems were specific predictors for behavioral regulation and cognitive function, respectively. Our findings suggested that treating common predictors in childhood, such as inattention, may potentially improve real-world executive function in autism during the transition into adulthood.

Social Brain Activation and Connectivity in Autism Spectrum Disorders: An Electroencephalogram Study of Jigsaw Puzzle Solving.

Autism spectrum disorder requires early detection and treatment. Thus, we developed a method to obtain reliable neurophysiological biomarkers to assist in diagnosing autism. This method includes a simple but typical jigsaw puzzle that allows participants to play and interact with each other. While playing this game, brain signals of the participants were observed and analyzed. The patients with autism were found to have differences in the time range of some event-related potential, such as P300 and N400. Altered patterns of function connectivity were also found in delta frequency bands in the patients while interacting with other people. Working around patients' capabilities, the jigsaw puzzle game was designed as easy to complete; this caused fewer mismatch conditions. The result suggested that these patterns are promising neurophysiological biomarker to assist doctors in social cognitive assessment in autism.Clinical Relevance-This study demonstrated the possibility of using hyperscanning technique for social cognitive assessment of autism spectrum disorder.

The clinical and sleep manifestations in children with FOXG1 syndrome.

FOXG1 syndrome is a rare neurodevelopmental disorder associated with severe cognitive dysfunction, autistic behavior, and early-onset hyperkinetic movement disorders. Patients have also been reported to experience sleep disturbances. However, these findings are mainly based on subjective caregivers' reports, and limited by small case numbers. Moreover, no studies using objective evaluation tools, such as actigraphy, have been reported. We analyzed the clinical and sleep manifestations of children with FOXG1 syndrome registered in the FOXG1 Research Foundation Patient Registry database. A total of 258 individuals with FOXG1 syndrome were included in this research. 132 (51.16%) had sleep disturbances. The more impaired of language acquisitions (absence of speech, OR: 3.99, 95%CI = 1.69-9.42, p = 0.002), hyperkinetic movement disorders (OR: 2.64, 95%CI = 1.34-5.20 p = 0.005) and feeding difficulties (OR: 2.81, 95% CI = 1.52-5.19, p = 0.001) were significantly associated with an increase in odds of sleep disturbance after adjusting for age, sex, and antiepileptic drugs. We also performed sleep studies on six individuals with FOXG1 syndrome using The Children's Sleep Habits Questionnaire (CSHQ), the Sleep Disturbance Scale for Children (SDSC), and 7-day data from Actiwatch. The Pittsburgh Sleep Quality Index (PSQI) and 7-day data from Actiwatch were also used to evaluate the sleep condition of their parents. The CSHQ scores revealed bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night-waking, and parasomnia. Sleep-wake transition disorders and disorders of initiating and maintaining sleep were also suggested by the SDSC scores. The children's actigraphy revealed short sleep durations, impaired sleep efficiency, longer wake after sleep onset, and frequent night-waking. All caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration. Sleep disturbances, especially in initiating and maintaining sleep, are common in individuals with FOXG1 syndrome and their caregivers. Sleep disorders in patients with FOXG1 syndrome and their caregivers should be investigated.

Effectiveness, durability, and clinical correlates of the PEERS social skills intervention in young adults with autism spectrum disorder: the first evidence outside North America.

BACKGROUND: Despite the fact that social deficits among individuals with autism spectrum disorder (ASD) are lifelong and impact many aspects of personal functioning, evidence-based programs for social skills training were not available until recently. The Program for the Education and Enrichment of Relational Skills (PEERS®) has been shown to effectively improve social skills for adolescents on the spectrum across different social cultures. However, the effectiveness for young adults beyond North America has yet to be examined. This study aimed to investigate the effectiveness of the PEERS intervention in Taiwanese young adults with ASD, and examine its durability and clinical correlates. METHODS: We recruited 82 cognitively-able young adults with ASD, randomized to the PEERS treatment or treatment-as-usual. RESULTS: Following treatment, significant improvement was found in aspects of social deficits, autism severity, social interaction anxiety, empathy, and social skills knowledge either by self-report or coach-report. Additionally, communicative behaviors rated by observers improved throughout the sessions, showing a trend toward more appropriate eye contact, gestures, facial expression during conversation, and appropriate maintenance of conversation and reciprocity. Most effects maintained at 3-month and 6-month follow-ups. The improvement of social deficits was positively correlated with baseline severity, while gains in social skills knowledge were positively correlated with IQ. The improvement of social deficits, autism severity, and empathy were positively correlated with each other. CONCLUSION: Overall, the PEERS intervention appears to effectively improve social functioning in Taiwanese young adults with ASD. Improvement of social response and knowledge may be predicted by baseline severity and intelligence respectively.

Developmental Changes of Autistic Symptoms, ADHD Symptoms, and Attentional Performance in Children and Adolescents with Autism Spectrum Disorder.

This study followed up ADHD/autistic symptoms and attentional performance in children/adolescents with ASD and typically developing ones (TD) over 5-7 years. The participants were stratified by age at baseline into child (< 12 years) and adolescent (12-19 years) groups. ADHD symptoms, especially hyperactivity, and attentional functions significantly improved during follow-up, more in children than in adolescents, in both ASD and TD. Significantly more omission errors and perseverations were noted in ASD than TD through the follow-up. Children with ASD had more improvement in reaction time while adolescents with ASD had less improvement in commission errors and detectability than TD. No correlation of attentional functions and ADHD symptoms in ASD implied different neural mechanisms of ADHD symptoms between ASD and ADHD.

Promotion and implementation effectiveness of World Health Organization's Caregiver Skills Training program in Taiwan.

The World Health Organization (WHO) developed the Caregiver Skills Training for Families of Children with Developmental Delays and Disabilities (CST) with support from Autism Speaks to address the resource gaps and worldwide needs for interventions for children with developmental disorders or delays, especially those with autism spectrum disorder (ASD), and their families. Evidence has indicated that parent-mediated interventions benefit both caregivers and children by strengthening caregivers' knowledge and confidence and children's social communication skills and behavioral regulation. The CST-Taiwan team began the prepilot field trial in 2017 and developed the project to serve families in various locations. This study (1) delineated the adaptations and promotion of CST-Taiwan; (2) determined the program's effectiveness in the promotional stage, in terms of caregiver and child outcomes, and (3) examined the maintenance of its effects. The materials, delivery, and facilitator training procedure of the original CST were adapted to Taiwan. The quantitative data indicated that CST-Taiwan is a promising program, it positively affected caregiver knowledge and confidence and reduced the severity of the children's autistic symptoms. The 3-month follow-up results suggested that the effects persisted. Thus, CST-Taiwan, and its promotional strategies are feasible and effective.

Psychopathologies mediate the link between autism spectrum disorder and bullying involvement: A follow-up study.

BACKGROUND/PURPOSE: Youths with autism spectrum disorder (ASD) are at a high risk of involvement in school bully. The study investigated whether comorbid psychopathologies mediated the link between ASD and bullying involvement. METHODS: We assessed 353 youths (mean age, 11.8 ± 3.1 years), including 121 youths with ASD and 232 typically developing (TD) controls, using semi-structured diagnostic interviews on ASD and other psychiatric conditions. Follow-up assessments took place 2-5 years (37.6 ± 15 months) later. Meanwhile, their parents reported on the Social Adjustment Inventory for Children and Adolescents about bullying involvement statuses. We identified significant mediators by simple mediation models, followed by multiple mediation models to scrutinize the mediation effects of selected mediators. RESULTS: The results showed a sevenfold increased risk of bullying involvement among youths with ASD compared with TD controls at follow-up. In general, psychopathologies mediated the link between ASD and bullying involvement, even independent of age and sex. Specifically, we found mediating effects of social problems on victimization-only and aggressive behaviors on victimization-perpetration. CONCLUSION: Our findings strongly suggest the link between ASD and later bullying involvement is mediated by pre-existing comorbid psychiatric conditions, besides the direct effect of ASD on bullying victimization. Hence, early identification and intervention of these psychopathologies are highly suggested.

Game-based Social Interaction Platform for Cognitive Assessment of Autism using Eye Tracking.

The design goals of recently developed serious games are to improve attention, affective recognition, and social interactions among individuals with autism. However, most previous studies on serious games used behavioral questionnaires to evaluate their effectiveness. The cognitive assessment of individuals with autism after behavioral intervention or drug treatment has become important because it provides promising biomarkers to assess improvement after cognitive intervention. In this study, we developed a game-based social interaction platform incorporating an eye-tracking system for children and preadolescents with autism. Three modules (focusing on gaze following, facial emotion recognition, and social interaction skills) are included in the platform; participants with autism learn these according to their cognitive abilities. The eye-tracking results showed decreased fixation durations when autistic children looked at positive emotional expressions and focused on multiple targets. Prolonged saccade durations and shorter fixation times for social-related facial emotion expressions were also found in preadolescents and teenagers with autism. Our findings suggest that these atypical gaze patterns are reliable biomarkers for evaluating the social and cognitive functions of autistic individuals while playing serious games. The proposed platform's game-based modules and the findings regarding aberrant gaze patterns in autistic individuals demonstrate the possibility of evaluating cognitive functions and intervention effectiveness by using eye-tracking signals in a serious game or real-life environment.

An immunochromatographic assay utilizing magnetic nanoparticles to detect major peanut allergen Ara h 1 in processed foods.

This study describes an immunomagnetic nanoparticle (IMNP)-based lateral flow assay (LFA) for detecting the major peanut allergen Ara h 1. We developed a clearly specific method in identifying peanut from ten other seeds and nuts, and a good visual limit of detection (vLOD) of 0.01 µg/mL Ara h 1 in PBS. PBS that contains 1 M NaCl and 2% Tween 20 was determined to be the optimal extraction buffer for isolating Ara h 1 from cookie, milk and chocolate with vLOD values of 0.5 µg/g, 0.5 µg/mL, and 1 µg/g, respectively. Forty two processed foods were simultaneously analyzed using this method and an AOAC-approved ELISA kit. The specificity and sensitivity of this assay were thus determined to be 100 and 95%, respectively. This new IMNP-based LFA has potential as a rapid tool for screening processed foods for Ara h 1 residues.

A translational exploration of the effects of WNT2 variants on altered cortical structures in autism spectrum disorder.

BACKGROUND: Evidence suggests that cortical anatomy may be aytpical in autism spectrum disorder. The wingless-type MMTV integration site family, member 2 (WNT2), a candidate gene for autism spectrum disorder, may regulate cortical development. However, it is unclear whether WNT2 variants are associated with altered cortical thickness in autism spectrum disorder. METHODS: In a sample of 118 people with autism spectrum disorder and 122 typically developing controls, we investigated cortical thickness using FreeSurfer software. We then examined the main effects of the WNT2 variants and the interactions of group × SNP and age × SNP for each hemisphere and brain region that was altered in people with autism spectrum disorder. RESULTS: Compared to neurotypical controls, people with autism spectrum disorder showed reduced mean cortical thickness in both hemispheres and 9 cortical regions after false discovery rate correction, including the right cingulate gyrus, the orbital gyrus, the insula, the inferior frontal gyrus (orbital part and triangular part), the lateral occipitotemporal gyrus, the posterior transverse collateral sulcus, the lateral sulcus and the superior temporal sulcus. In the full sample, 2 SNPs of WNT2 (rs6950765 and rs2896218) showed age × SNP interactions for the mean cortical thickness of both hemispheres, the middle-posterior cingulate cortex and the superior temporal cortex. LIMITATIONS: We examined the genetic effect for each hemisphere and the 9 regions that were altered in autism spectrum disorder. The age effect we found in this cross-sectional study needs to be examined in longitudinal studies. CONCLUSION: Based on neuroimaging and genetic data, our findings suggest that WNT2 variants might be associated with altered cortical thickness in autism spectrum disorder. Whether and how these WNT2 variants might involve cortical thinning requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT01582256. PROTOCOL REGISTRATION: National Institutes of Health no. NCT00494754.

Dietary intake and growth deficits in Rett syndrome-A cross-section study.

Growth deficit is a common comorbidity and one of the supportive criteria in Rett syndrome (RTT). This study aimed to investigate the impact of dystonia, dietary intakes, and clinical severities on growth patterns in a Taiwanese cohort of RTT. We recruited 44 RTT patients with MECP2 mutation for analysis. For individuals ≤18 years of age, in comparison to the RTT-specific growth chart which comprised American RTT cohort, the body height was right-shifted to a higher percentile, whereas the body weight was left-shifted to a lower percentile. Furthermore, the body mass index was significantly decreased when compared to RTT-specific growth chart (p = 0.01). Higher degree of overall disease severity (odd ratio = 1.159; 95% CI = 1.063-1.264; p = 0.001) and hand use impairment (odd ratio = 2.017; 95% CI = 1.037, 3.921; p = 0.039) were associated with more severe growth patterns. All individuals had dystonia at certain variable degrees. The dystonia worsened with age (p < 0.001) but did not have significant impact on growth deficit. Most of our cohort had adequate protein (97.37%) and energy (58.97%) intakes. The fiber intakes were generally low, with about 38 (97.4%) individuals did not meet the daily reference intakes of fiber. The protein intake was significantly lower in individuals with severe growth deficit (p = 0.04). Our study shows that ethnicity should be considered when comparing RTT individuals' growth pattern to the RTT-specific growth chart. Further, disease severity, genotypes, and nutrition exert important impacts on RTT-growth pattern. LAY SUMMARY: Growth impairment is an important issue in Rett syndrome and the underlying patho-mechanism is multifactorial. Higher degree of overall disease severity and hand use impairment were associated with more severe growth pattern deficits. Although all individuals had dystonia at certain variable degrees and the dystonia worsened with age, but it did not have significant impact on growth deficit. Nutritional intakes may partially affect growth. Furthermore, ethnicity should be considered when comparing RTT individuals' growth pattern to the RTT-specific growth chart.

Executive functions in youths with autism spectrum disorder and their unaffected siblings.

BACKGROUND: Executive dysfunction is one of the main cognitive theories of autism spectrum disorder (ASD). Despite evidence of deficits in executive functions in individuals with ASD, little is known about executive dysfunctions as candidate cognitive endophenotypes for ASD. In this study, we investigated executive functions in youths with ASD, their unaffected siblings and typically developing controls (TDC). METHODS: We recruited 240 youths with a clinical diagnosis of ASD (aged 6-18 years), 147 unaffected siblings of ASD youths, and 240 TDC youths. TDC youths were recruited based on the age and sex distribution of the ASD youths. Participants were assessed using the verbal Digit Span test and four executive function tasks from the Cambridge Neuropsychological Test Automated Battery, including Intra-dimensional/Extra-dimensional Shift (I/ED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stocking of Cambridge (SoC). RESULTS: ASD youths, relative to TDC, performed significantly worse in executive function tasks assessing verbal working memory (forward and backward digit span), set-shifting (I/ED), visuospatial working memory (SSP, SWM), and planning/problem solving (SoC). Furthermore, unaffected siblings, relative to TDC, performed worse in forward and backward digit recalls and made more errors in SWM. These results were independent of the effects of age, sex, IQ, and symptoms of attention-deficit/hyperactivity disorder. CONCLUSIONS: Our findings support impaired executive functions in youths with ASD. However, unaffected siblings were mostly unimpaired except in the areas of verbal and spatial working memory, which may be potential cognitive endophenotypes for ASD.

Small fiber pathology in autism and clinical implications.

OBJECTIVE: To investigate small fiber innervation of the skin and its relationships with clinicometry of autism and peripheral afferents for contact heat-evoked potential (CHEP) and psychophysical measures of thermal thresholds. METHODS: We recruited 32 men with autism (26.5 ± 5.9 years) and conducted small fiber assessments of skin biopsy with quantifying intraepidermal nerve fiber (IENF) density, CHEP, quantitative sensory testing, and large fiber physiology of nerve conduction studies. Results were compared with age-matched controls and analyzed with clinical measures of autism. RESULTS: Patients with autism showed a lower IENF density than controls (5.53 ± 2.09 vs 11.13 ± 3.49 fibers/mm, p < 0.0001). The IENF density was reduced in 17 (53.1%) men with autism classified as skin denervation group. On psychophysics, 9 (28%) men with autism had elevated thermal thresholds, and the warm threshold of the big toe was negatively correlated with IENF density (p = 0.0073), indicating functional impairments of small fiber sensory nerves. IENF density was negatively correlated with CHEP amplitude in autism (p = 0.003), in contrast to the pattern of positive correlation in controls, indicating different processing of nociceptive afferent in autism. Clinically, IENF density was related to distinct tactile symptom patterns in the skin denervation vs normal innervation group, respectively. Furthermore, IENF density was associated with autistic symptoms measured by the Autism Spectrum Quotient in a U-shaped model (p = 0.014). CONCLUSIONS: These observations indicated that a substantial portion of individuals with autism had small fiber pathology, which was associated with tactile and autistic symptoms, providing structural and physiologic evidence for the involvement of peripheral sensory nerves in autism.

The protective ability and cellular mechanism of Koelreuteria henryi Dummer flower extract against hydrogen peroxide-induced cellular oxidative damage

BACKGROUND: Koelreuteria henryi Dummer is an indigenous plant in Taiwan. The species has been used in traditional folk medicine for the promotion of liver functions and for treating malaria and urethritis. The present study investigated the antioxidant activity of the flower extract of Koelreuteria henryi Dummer. The extraction conditions were optimized by the contents of total phenolic acids and total flavonoids, and antioxidant activity assays. Moreover, an in vitro study for investigating antioxidant activity of K. henryi flower extract was demonstrated by hydrogen peroxide (H2O2)-induced apoptosis. RESULTS: K. henryi flower extracted for 150 min showed high contents of total phenolic acids and total flavonoids. In an in vitro model, L929 cells were pretreated with K. henryi flower extract, and then treated with H2O2 to induce oxidative damage. Results demonstrated that H2O2-induced apoptosis was inhibited by the treatment of 200 µg/ml K. henryi flower extract through the mitochondria-mediated pathway and mitogen-activated protein kinase (MAPK) pathway. The caspase 8/9 activity and expression of p-p38 and pERK were repressed by K. henryi flower extract. In addition, the prevention of H2O2-induced apoptosis by K. henryi flower extract activated the nuclear factor-erythroid 2-related factor (Nrf2) stress response pathway to transcript heme oxygenase 1 (HO-1). Also, K. henryi flower extract prevented H2O2-induced apoptosis through HO-1 production, as evident by the use of HO-1 inhibitor. CONCLUSIONS: The present study demonstrated that K. henryi flower extract could inhibit the H2O2-induced apoptosis in L929 cells through the activation of the Nrf2/HO-1 pathway.