GENES BIOMARKERS IN AUTISM: BRAIN DEVELOPMENT AND FUNCTION

Autism is childhood neuropsychiatric disorder despite exhibiting high heritability and has largely eluded efforts to identify specific genetic variants of biomarkers. This neuropsychiatric disorder is characterized by social and communicative deficits and ritualistic-repetitive behaviour that are detectable in early childhood. It has been reported that some candidate genes has been found in autism children brains. The candidate genes include aspects of neurogenesis, neuronal migration, maturation, differentiation, and degeneration. Some of researchers had reported the effects of the mutated and sufficiency of the candidate genes in autism brain which believed that might involved in the mechanism and causes deficit in social behaviour language impairment and repetitive behaviour. In this review, we will summarize the gene candidate which found in autism children brains and their effect of their cognitive function. Keywords: Autism; Gene biomarkers; Brain development

GENES BIOMARKERS IN AUTISM: BRAIN DEVELOPMENT AND FUNCTION

Autism is childhood neuropsychiatric disorder despite exhibiting high heritability and has largely eluded efforts to identify specific genetic variants of biomarkers. This neuropsychiatric disorder is characterized by social and communicative deficits and ritualistic-repetitive behaviour that are detectable in early childhood. It has been reported that some candidate genes has been found in autism children brains. The candidate genes include aspects of neurogenesis, neuronal migration, maturation, differentiation, and degeneration. Some of researchers had reported the effects of the mutated and sufficiency of the candidate genes in autism brain which believed that might involved in the mechanism and causes deficit in social behaviour language impairment and repetitive behaviour. In this review, we will summarize the gene candidate which found in autism children brains and their effect of their cognitive function. Keywords: Autism; Gene biomarkers; Brain development

Antioxidant properties of stingless bee honey and its effect on the viability of lymphoblastoid cell line

Research on the medical benefit of stingless bee honey (kelulut honey) is rather new although it has been used as traditional food and additive for ages. The primary objective of our study was to evaluate the antioxidant properties of kelulut honey and its effect on lymphoblastoid cell line. We analysed the antioxidant properties of kelulut honey by ferric reducing antioxidant potential assay, total phenolic and flavonoid contents using UV spectrophotometry. The total phenolic content, total flavonoid content and ferric reducing antioxidant potential of Malaysian kelulut honey produced by Trigona spp. were found to be 844.45 mg RE/kg honey, 78.29 mg RE/kg honey and 1132.66 mM FE/kg honey, respectively. Our findings showed a strong correlation between total phenolics and flavanoids contents with its antioxidant potential at R2 = 0.920 and R2 = 0.951, respectively. The effect of honey on cell viability of lymphoblastoid cell line (LCL) was also investigated. The cells were cultured in RPMI-1640 medium supplemented with 0 - 500 μg/mL of kelulut honey for 24 hours. Cell viability was quantitated using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, MTS assay showed that honey supplementation boosted the viability of LCL up to 164.64% (p< 0.01). The significant increase in cell viability might be modulated by the antioxidant properties of kelulut honey

Hot water extract from saccharomyces cerevisiae scavenges dpph and reduces senescence associated β-Galactosidase (Sa-β-Gal) in human dermal fibroblasts

Extracts from Saccharomyces cerevisiae are incorporated in a lot of cosmetic products on the market, but the benefits of the extracts lack scientific reports. We tested the toxicity and anti-senescent activity of an extract from S. cerevisiae on an in vitro model, the human dermal fibroblast (HDF) cell culture. We chronicled the development of the extraction method and the subsequent biochemical assays. We used two extraction methods which were hot water extraction and rapid spin. The optimum duration and growth phase to harvest S. cerevisiae were determined by 2,2-diphenyl-1- picrylhydrazyl (DPPH) assay, which also proved that the extracts exhibited antioxidant activity. Hot water extract showed a higher antioxidant activity, and not toxic to HDF. When subjected to senescence-associated β-galactosidase (SA-β-al) assay, the hot water extract significantly reduced the expression of SA-β-Gal in pre-senescent (passage 20, 30 < population doubling 50) HDF. In conclusion, S. cerevisiae hot water extract possessed antioxidant activity by scavenging DPPH, and anti-senescent activity by reducing the expression of SA-β-Gal in pre-senescent and senescent HDF

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Tocotrienol-Rich Fraction (TRF) Treatment Promotes Proliferation Capacity of Stress-Induced Premature Senescence Myoblasts and Modulates the Renewal of Satellite Cells: Microarray Analysis

International audienceHuman skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50 μg/mL TRF treatment after SIPS induction). The differential gene expressions were assessed using microarray, GSEA, and KEGG pathway analysis. Results showed that TRF treatment significantly regulated the gene expressions, i.e., p53 (RRM2B, SESN1), ErbB (EREG, SHC1, and SHC3), and FoxO (MSTN, SMAD3) signalling pathways in the SIPS myoblasts compared to the SIPS control group (). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways

Reversal of Myoblast Aging by Tocotrienol Rich Fraction Posttreatment

Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associated β-galactosidase (SA-β-galactosidase), and cell proliferation were determined. 50 μg/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA-β-galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA-β-galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA-β-galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed

Senescence-Related Changes in Gene Expression of Peripheral Blood Mononuclear Cells from Octo/Nonagenarians Compared to Their Offspring

Mechanisms determining both functional rate of decline and the time of onset in aging remain elusive. Studies of the aging process especially those involving the comparison of long-lived individuals and young controls are fairly limited. Therefore, this research aims to determine the differential gene expression profile in related individuals from villages in Pahang, Malaysia. Genome-wide microarray analysis of 18 samples of peripheral blood mononuclear cells (PBMCs) from two groups: octo/nonagenarians (80–99 years old) and their offspring (50.2 ± 4.0 years old) revealed that 477 transcripts were age-induced and 335 transcripts were age-repressed with fold changes ≥1.2 in octo/nonagenarians compared to offspring. Interestingly, changes in gene expression were associated with increased capacity for apoptosis (BAK1), cell cycle regulation (CDKN1B), metabolic process (LRPAP1), insulin action (IGF2R), and increased immune and inflammatory response (IL27RA), whereas response to stress (HSPA8), damage stimulus (XRCC6), and chromatin remodelling (TINF2) pathways were downregulated in octo/nonagenarians. These results suggested that systemic telomere maintenance, metabolism, cell signalling, and redox regulation may be important for individuals to maintain their healthy state with advancing age and that these processes play an important role in the determination of the healthy life-span

Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation

Abstract 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