A Link between Mitochondrial Dysregulation and Idiopathic Autism Spectrum Disorder (ASD): Alterations in Mitochondrial Respiratory Capacity and Membrane Potential.

Autism spectrum disorder (ASD) is a neurological disorder triggered by various factors through complex mechanisms. Research has been done to elucidate the potential etiologic mechanisms in ASD, but no single cause has been confirmed. The involvement of oxidative stress is correlated with ASD and possibly affects mitochondrial function. This study aimed to elucidate the link between mitochondrial dysregulation and idiopathic ASD by focusing on mitochondrial respiratory capacity and membrane potential. Our findings showed that mitochondrial function in the energy metabolism pathway was significantly dysregulated in a lymphoblastoid cell line (LCL) derived from an autistic child (ALCL). Respiratory capacities of oxidative phosphorylation (OXPHOS), electron transfer of the Complex I and Complex II linked pathways, membrane potential, and Complex IV activity of the ALCL were analyzed and compared with control cell lines derived from a developmentally normal non-autistic sibling (NALCL). All experiments were performed using high-resolution respirometry. Respiratory capacities of OXPHOS, electron transfer of the Complex I- and Complex II-linked pathways, and Complex IV activity of the ALCL were significantly higher compared to healthy controls. Mitochondrial membrane potential was also significantly higher, measured in the Complex II-linked pathway during LEAK respiration and OXPHOS. These results indicate the abnormalities in mitochondrial respiratory control linking mitochondrial function with autism. Correlating mitochondrial dysfunction and autism is important for a better understanding of ASD pathogenesis in order to produce effective interventions.

Do Temporal Eating Patterns Differ in Healthy versus Unhealthy Overweight/Obese Individuals?

This study examined whether the temporal patterns of energy and macronutrient intake in early and late eating windows were associated with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) among non-shift workers. A total of 299 overweight/obese non-shift workers (Age: 40.3 ± 6.9 years; 73.6% women; BMI: 31.7 ± 5.0 kg/m2) were recruited in the Klang Valley area of Malaysia. The biochemical parameters were determined from fasting blood samples, whereas information on dietary intake and timing was obtained from a 7-day diet history questionnaire. The midpoint of eating was used to determine the early and late windows. Compared to MHO non-shift workers (n = 173), MUO non-shift workers (n = 126) had lower energy intake from carbohydrates and protein during the early window. In contrast, MUO participants had greater energy intake from carbohydrates and fat during the late window. Participants with unhealthy metabolic status (regardless of their chronotypes) had similar temporal patterns of energy intake characterized by smaller energy intake during the early window and greater energy intake during the late window compared with participants with healthier metabolic status. Overall, the lowest percentile of energy intake during the early window was associated with an increased risk of MUO, after adjustment for potential confounders [odds ratio (OR) = 4.30, 95% confidence interval (CI) 1.41-13.11]. The greater the energy intake during the late window, the greater the risk of MUO (OR = 2.38, 95% CI 1.11-5.13) (OR = 2.33, 95% CI 1.03-5.32) (OR = 4.45, 95% CI 1.71-11.56). In summary, consuming less energy earlier in the day and more energy and carbohydrate later in the day was associated with a greater risk of MUO. Thus, a prospective study is needed to explore the potential role of chrono-nutrition practices in modifying risk factors to delay the transition of MHO to MUO.

Modified Munich chronotype questionnaire for application to short-interval split sleep of non-shift workers.

The Munich Chronotype Questionnaire (MCTQ) has been widely validated among various types of populations. However, determination of chronotype among individuals who have a split sleep pattern with short intervals between the first and second sleep bouts on free days has not yet been reported. This study aimed to validate the MCTQ modified for this purpose by assessing the actual sleep-wake timing against the Morningness-Eveningness Questionnaire (MEQ). The modified calculation for the midpoint of sleep on free days (MSF) of the split sleep pattern considers the second sleep bout as the total sleep duration on free days. We recruited 161 participants (mean age: 38.7 ± 7.8 years; 73% females, 29% with split sleep pattern) were recruited to administer the modified version of the MCTQ and MEQ. All of the MCTQ original parameters: midpoint of sleep on work days (MSW, r = -0.575), midpoint of sleep on free days (MSF, r = -0.568), and midpoint of sleep on free days corrected for sleep debt (MSFsc,r = -0.566) were significantly correlated with MEQ. The MEQ was further tested against MSF in four conditions of the split sleep pattern. The MSF modified for split sleep within 60 minutes after the first awakening showed highest correlation (r = -0.576) against MEQ score. The results demonstrate the modified version of MCTQ is valid to determine the chronotype in participants who practice consolidated and split sleep patterns.

In Vitro Modulation of Endogenous Antioxidant Enzyme Activities and Oxidative Stress in Autism Lymphoblastoid Cell Line (ALCL) by Stingless Bee Honey Treatment.

Autism has been associated with a low antioxidant defense mechanism, while honey has been known for decades for its antioxidant and healing properties. Determination of stingless bee honey (KH) effects on antioxidant enzyme activities and oxidative damage in Autism Lymphoblastoid Cell Line (ALCL) was performed. ALCL and its normal sibling pair (NALCL) were cultured in RPMI-1640 medium at 37°C and 5% CO2. ALCL was treated with 400 µg/mL KH (24 h), and oxidative stress marker, malondialdehyde (MDA), and antioxidant enzyme activities (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured via enzyme-linked immunosorbent assay (ELISA), while deoxyribonucleic acid (DNA) damage was determined via comet assay. Low SOD activity (p < 0.05) and high MDA level (p < 0.05) were observed in ALCL compared to NALCL. Higher grade (Grades 2 and 3) of DNA damage was highly observed (p < 0.05) in ALCL compared to NALCL, whereas lower grade (Grades 0 and 1) DNA damage was highly detected (p < 0.05) in NALCL compared to ALCL. KH treatment caused a significant increase in SOD and GPx activities (p < 0.05) in ALCL compared to untreated ALCL. Correspondingly, KH treatment reduced the Grade 2 DNA damage (p < 0.05) in ALCL compared to untreated ALCL. CAT activity showed no significant difference between all three groups, while the MDA level showed no significant difference between treated and untreated ALCL. In conclusion, KH treatment significantly reduced the oxidative stress in ALCL by increasing the SOD and GPx antioxidant enzyme activities, while reducing the DNA damage.

Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation.

BACKGROUND: Several muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 µg/mL TRF for 24 h before and after inducing differentiation. RESULTS: The fusion index and myotube surface area were higher (p < 0.05) on days 3 and 5 than that on day 1 of differentiation. Ageing reduced the differentiation rate, as observed by a decrease in both fusion index and myotube surface area in senescent cells (p < 0.05). Treatment with TRF significantly increased differentiation at days 1, 3 and 5 of young and senescent myoblasts. In senescent myoblasts, TRF increased the expression of miR-206 and miR-486 and decreased PTEN and PAX7 expression. However, the expression of IGF1R was upregulated during early differentiation and decreased at late differentiation when treated with TRF. In young myoblasts, TRF promoted differentiation by modulating the expression of miR-206, which resulted in the reduction of PAX7 expression and upregulation of IGF1R. CONCLUSION: TRF can potentially promote myoblast differentiation by modulating the expression of myomiRs, which regulate the expression of myogenic genes.

Gelam and Nenas honeys inhibit proliferation of HT 29 colon cancer cells by inducing DNA damage and apoptosis while suppressing inflammation.

Gelam and Nenas monofloral honeys were investigated in this study for their chemopreventive effects against HT 29 colon cancer cells. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolim) assays showed more effective inhibition of colon cancer cells proliferation by Gelam honey with IC50 values of 39.0 mg/ml and 85.5 mg/ml respectively after 24 hours of treatment. Alkali comet assays revealed both honeys increased DNA damage significantly in a dose dependent manner. In addition, annexin V-FITC/PI flow cytometry demonstrated that at IC50 concentrations and above, both Gelam and Nenas honeys induced apoptosis significantlyat values higher than for necrosis (p<0.05). Measurement of prostaglandin E2 (PGE2) confirmed that Gelam and Nenas honeys reduced its production in H2O2 inflammation-induced colon cancer cells. In conclusion, our study indicated and confirmed that both Gelam and Nenas honeys are capable of suppressing the growth of HT 29 colon cancer cells by inducing apoptosis and suppressing inflammation.