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Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways

Wee LH, Morad NA, Aan GJ, Makpol S, Wan Ngah WZ, Mohd Yusof YA

Asian Pac J Cancer Prev, 2015;16(15):6549-56.
PMID: 26434873

The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.

Matched MeSH terms: Glycogen Synthase Kinase 3/genetics; Glycogen Synthase Kinase 3 beta
Fulltext Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

Tan JN, Mohd Saffian S, Buang F, Jubri Z, Jantan I, Husain K, et al.

Front Pharmacol, 2020;11:504624.
PMID: 33328981 DOI: 10.3389/fphar.2020.504624

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as "Gynura," "antioxidant," "anti-inflammatory," or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

Matched MeSH terms: Glycogen Synthase Kinase 3
Fulltext Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus-A Review of Potential Contributing Mechanisms

John CM, Mohamed Yusof NIS, Abdul Aziz SH, Mohd Fauzi F

Int J Mol Sci, 2018 Dec 05;19(12).
PMID: 30563117 DOI: 10.3390/ijms19123894

Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta
Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients

Abdullah IS, Teh SH, Khaidizar FD, Ngu LH, Keng WT, Yap S, et al.

Genes Genomics, 2019 08;41(8):885-893.
PMID: 31028654 DOI: 10.1007/s13258-019-00815-9

BACKGROUND: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown.
OBJECTIVE: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population.
METHODS: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay.
RESULTS: We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%).
CONCLUSION: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested.

Matched MeSH terms: Glycogen Debranching Enzyme System/genetics*; Glycogen Debranching Enzyme System/metabolism; Glycogen Storage Disease Type III/genetics*; Glycogen Storage Disease Type III/pathology
Standardized Morinda citrifolia L. and Morinda elliptica L. leaf extracts alleviated fatigue by improving glycogen storage and lipid/carbohydrate metabolism

Osman WNW, Mohamed S

Phytother Res, 2018 Oct;32(10):2078-2085.
PMID: 29993148 DOI: 10.1002/ptr.6151

The antifatigue properties of Morinda elliptica (ME) leaf were compared with Morinda citrifolia (MC) leaf extracts. Sixty Balb/C mice were administered (N = 10): control water, standardized green tea extract (positive control 200 mg/kg body weight [BW]), either 200 or 400 mg MC/kg BW, or either 200 or 400 mg ME/kg BW). The mice performances, biochemical, and mRNA expressions were evaluated. After 6 weeks, the weight-loaded swimming time to exhaustion in the mice consuming 400 mg MC/kg, were almost five times longer than the control mice. The gene expressions analysis suggested the extracts enhanced performance by improving lipid catabolism, carbohydrate metabolism, electron transport, antioxidant responses, energy production, and tissue glycogen stores. The MC and ME extracts enhanced stamina by reducing blood lactate and blood urea nitrogen levels, increasing liver and muscle glycogen reserve through augmenting the glucose metabolism (glucose transporter type 4 and pyruvate dehydrogenase kinase 4), lipid catabolism (acyl-Coenzyme A dehydrogenases and fatty acid translocase), antioxidant (superoxide dismutase 2) defence responses, electron transport (COX4I2), and energy production (PGC1α, NRF1, NRF2, cytochrome C electron transport, mitochondrial transcription factor A, UCP1, and UCP3) biomarkers. The MC (containing scopoletin and epicatechin) was better than ME (containing only scopoletin) or green tea (containing epicatechin and GT catechins) for alleviating fatigue.

Matched MeSH terms: Glycogen/metabolism*
Could protein phosphatase 2A and glycogen synthase kinase-3 beta be targeted by natural compounds to ameliorate Alzheimer's pathologies?

Manoharan SD, Abdul Hamid H, Md Hashim NF, Cheema MS, Chiroma SM, Mustapha M, et al.

Brain Res, 2024 Apr 15;1829:148793.
PMID: 38309553 DOI: 10.1016/j.brainres.2024.148793

Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and cognitive abilities, primarily in the elderly. The burden of AD extends beyond patients, impacting families and caregivers due to the patients' reliance on assistance for daily tasks. The main features of the pathogenesis of AD are beta-amyloid plaques and neurofibrillary tangles (NFTs), that strongly correlate with oxidative stress and inflammation. NFTs result from misfolded and hyperphosphorylated tau proteins. Various studies have focused on tau phosphorylation, indicating protein phosphatase 2A (PP2A) as the primary tau phosphatase and glycogen synthase kinase-3 beta (GSK-3β) as the leading tau kinase. Experimental evidence suggests that inhibition of PP2A and increased GSK-3β activity contribute to neuroinflammation, oxidative stress, and cognitive impairment. Hence, targeting PP2A and GSK-3β with pharmacological approaches shows promise in treating AD. The use of natural compounds in the drug development for AD have been extensively studied for their antioxidant, anti-inflammatory, anti-cholinesterase, and neuroprotective properties, demonstrating therapeutic advantages in neurological diseases. Alongside the development of PP2A activator and GSK-3β inhibitor drugs, natural compounds are likely to have neuroprotective effects by increasing PP2A activity and decreasing GSK-3β levels. Therefore, based on the preclinical and clinical studies, the potential of PP2A and GSK-3β as therapeutic targets of natural compounds are highlighted in this review.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/metabolism
Environmental changes affecting physiological responses and growth of hybrid grouper - The interactive impact of low pH and temperature

Thalib YA, Razali RS, Mohamad S, Zainuddin R', Rahmah S, Ghaffar MA, et al.

Environ Pollut, 2021 Feb 15;271:116375.
PMID: 33422747 DOI: 10.1016/j.envpol.2020.116375

Rising of temperature in conjunction with acidification due to the anthropogenic climates has tremendously affected all aquatic life. Small changes in the surrounding environment could lead to physiological constraint in the individual. Therefore, this study was designed to investigate the effects of warm water temperature (32 °C) and low pH (pH 6) on physiological responses and growth of hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) juveniles for 25 days. Growth performance was significantly affected under warm water temperature and low-pH conditions. Surprisingly, the positive effect on growth was observed under the interactive effects of warm water and low pH exposure. Hybrid grouper exposed to the interactive stressor of warm temperature and low pH exhibited higher living cost, where HSI content was greatly depleted to about 2.3-folds than in normal circumstances. Overall, challenge to warm temperature and low pH induced protein mobilization as an energy source followed by glycogen and lipid to support basal metabolic needs.

Matched MeSH terms: Glycogen
Fulltext Female tilapia, Oreochromis sp. mobilised energy differently for growth and reproduction according to living environment

Razali RS, Rahmah S, Shirly-Lim YL, Ghaffar MA, Mazelan S, Jalilah M, et al.

Sci Rep, 2024 Feb 05;14(1):2903.
PMID: 38316820 DOI: 10.1038/s41598-024-52864-0

This study was conducted to investigate the energy mobilisation preference and ionoregulation pattern of female tilapia, Oreochromis sp. living in different environments. Three different treatments of tilapia as physiology compromising model were compared; tilapia cultured in recirculating aquaculture system (RAS as Treatment I-RAS), tilapia cultured in open water cage (Treatment II-Cage) and tilapia transferred from cage and cultured in RAS (Treatment III-Compensation). Results revealed that tilapia from Treatment I and III mobilised lipid to support gonadogenesis, whilst Treatment II tilapia mobilised glycogen as primary energy for daily exercise activity and reserved protein for growth. The gills and kidney Na+/K+ ATPase (NKA) activities remained relatively stable to maintain homeostasis with a stable Na+ and K+ levels. As a remark, this study revealed that tilapia strategized their energy mobilisation preference in accessing glycogen as an easy energy to support exercise metabolism and protein somatogenesis in cage culture condition, while tilapia cultured in RAS mobilised lipid for gonadagenesis purposes.

Matched MeSH terms: Glycogen/metabolism
Fulltext Aggressive variant large granular lymphocytic leukaemia: a case report

Sabariah, M. N., Zainina, S., Faridah, I., Leong, C. F.

Malaysian Journal of Medicine and Health Sciences, 2011;7(1):57-60.
MyJurnal

Clonal disorders of LGL may either be CD3+ CD56- or CD3- CD56+ phenotype and these have been designated as T-cell leukaemia (T-LGL) or natural killer cell (NK)-LGL leukaemia respectively. Clonality is usually demonstrated by clonal rearrangement of T-cell receptor gene rearrangement or identified by flowcytometry analysis. Most patients with T-LGL will have an indolent course. In this report we described an aggressiveness of disease in a patient with clonal CD3+ LGL leukaemia whose cells also co-expressed CD56 diagnosed by flowcytometry. The patient responded well to interrupt ALL standard risk protocol however succumbed to her disease while waiting for upfront stem cell transplant. This case highlights on both the classical laboratory findings of rare entity of disease as well as a review of the literature pertaining particularly on its management.

Matched MeSH terms: Glycogen Storage Disease Type VI
Efficacy of methylprednisolone on T-2 toxin-induced cardiotoxicity in vivo: A pathohistological study

Jaćević V, Wu Q, Nepovimova E, Kuča K

Environ Toxicol Pharmacol, 2019 Oct;71:103221.
PMID: 31365892 DOI: 10.1016/j.etap.2019.103221

Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p 

Matched MeSH terms: Glycogen
Cardiomyopathy induced by T-2 toxin in rats

Jaćević V, Wu Q, Nepovimova E, Kuča K

Food Chem Toxicol, 2020 Jan 22.
PMID: 31981685 DOI: 10.1016/j.fct.2020.111138

T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD50.) to Wistar rats. The cardiac tissue was carefully examinated by using basic histopathology, semiquantitative (tissue grading score scales) and imaging (a total number of mast cells - MCs) analyses on days 1, 7, 14, 21, 28 and 60 of the study. The most intensive myocardial alterations (cardiac damage score, CDS = 4.20-4.40), irregular glycogen distribution (glycogen distribution score, GDS = 4.07-4.17), haemorrhagic foci (vascular damage score, VDS = 4.57-4.90), diffuse accumulation and degranulation of MCs were observed on day 28 and 60 after treatment (p glycogen distribution and intensity of haemorrhage, and a negative correlation was found in the case of MCs. Obtained results are essential and crucial for further in vivo experimental studies, including the development of medications able to reduce T-2 toxin-induced cardiotoxicity.

Matched MeSH terms: Glycogen
Fulltext Assessment of RNA extraction protocols from cladocerans

Razak MR, Aris AZ, Md Yusoff F, Yusof ZNB, Kim SD, Kim KW

PLoS One, 2022;17(4):e0264989.
PMID: 35472091 DOI: 10.1371/journal.pone.0264989

The usage of cladocerans as non-model organisms in ecotoxicological and risk assessment studies has intensified in recent years due to their ecological importance in aquatic ecosystems. The molecular assessment such as gene expression analysis has been introduced in ecotoxicological and risk assessment to link the expression of specific genes to a biological process in the cladocerans. The validity and accuracy of gene expression analysis depends on the quantity, quality and integrity of extracted ribonucleic acid (RNA) of the sample. However, the standard methods of RNA extraction from the cladocerans are still lacking. This study evaluates the extraction of RNA from tropical freshwater cladocerans Moina micrura using two methods: the phenol-chloroform extraction method (QIAzol) and a column-based kit (Qiagen Micro Kit). Glycogen was introduced in both approaches to enhance the recovery of extracted RNA and the extracted RNA was characterised using spectrophotometric analysis (NanoDrop), capillary electrophoresis (Bioanalyzer). Then, the extracted RNA was analysed with reverse transcription polymerase chain reaction (RT-PCR) to validate the RNA extraction method towards downstream gene expression analysis. The results indicate that the column-based kit is most suitable for the extraction of RNA from M. micrura, with the quantity (RNA concentration = 26.90 ± 6.89 ng/μl), quality (A260:230 = 1.95 ± 0.15, A280:230 = 1.85 ± 0.09) and integrity (RNA integrity number, RIN = 7.20 ± 0.16). The RT-PCR analysis shows that the method successfully amplified both alpha tubulin and actin gene at 33-35 cycles (i.e. Ct = 32.64 to 33.48). The results demonstrate that the addition of glycogen is only suitable for the phenol-chloroform extraction method. RNA extraction with high and comprehensive quality control assessment will increase the accuracy and reliability of downstream gene expression, thus providing more ecotoxicological data at the molecular biological level on other freshwater zooplankton species.

Matched MeSH terms: Glycogen
Using SERS-based microfluidic paper-based device (μPAD) for calibration-free quantitative measurement of AMI cardiac biomarkers

Lim WY, Goh CH, Thevarajah TM, Goh BT, Khor SM

Biosens Bioelectron, 2020 Jan 01;147:111792.
PMID: 31678828 DOI: 10.1016/j.bios.2019.111792

Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based μPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based μPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based μPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.

Matched MeSH terms: Glycogen Phosphorylase/blood*
Cellular and hormonal control in glycogen metabolism--recent advances

Thambyrajah V, Karunairatnam MC

Med J Malaya, 1972 Sep;27(1):33-9.
PMID: 4345646
Matched MeSH terms: Glycogen/biosynthesis; Glycogen/metabolism*; Glycogen Synthase/metabolism
Fulltext A Review on the Crosstalk between Insulin and Wnt/β-Catenin Signalling for Bone Health

Wong SK, Mohamad NV, Jayusman PA, Ibrahim N'

Int J Mol Sci, 2023 Aug 04;24(15).
PMID: 37569816 DOI: 10.3390/ijms241512441

A positive association between insulin resistance and osteoporosis has been widely established. However, crosstalk between the signalling molecules in insulin and Wingless (Wnt)/beta-(β-)catenin transduction cascades orchestrating bone homeostasis remains not well understood. The current review aims to collate the existing evidence, reporting (a) the expression of insulin signalling molecules involved in bone-related disorders and (b) the expression of Wnt/β-catenin signalling molecules involved in governing insulin homeostasis. The downstream effector molecule, glycogen synthase kinase-3 beta (GSK3β), has been identified to be a point of convergence linking the two signal transduction networks. This review highlights that GSK3β may be a drug target in the development of novel anabolic agents and the potential use of GSK3β inhibitors to treat bone-related disorders.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/metabolism
Kinetic and stoichiometric characterization for efficient enhanced biological phosphorus removal (EBPR) process at high temperatures

Liau KF, Shoji T, Ong YH, Chua AS, Yeoh HK, Ho PY

Bioprocess Biosyst Eng, 2015 Apr;38(4):729-37.
PMID: 25381606 DOI: 10.1007/s00449-014-1313-3

A recently reported stable and efficient EBPR system at high temperatures around 30 °C has led to characterization of kinetic and stoichiometric parameters of the Activated Sludge Model no. 2d (ASM2d). Firstly, suitable model parameters were selected by identifiability analysis. Next, the model was calibrated and validated. ASM2d was found to represent the processes well at 28 and 32 °C except in polyhyroxyalkanoate (PHA) accumulation of the latter. The values of the kinetic parameters for PHA storage (q PHA), polyphosphate storage (q PP) and growth (μ PAO) of polyphosphate-accumulating organisms (PAOs) at 28 and 32 °C were found to be much higher than those reported by previous studies. Besides, the value of the stoichiometric parameter for the requirement of polyphosphate for PHA storage (Y PO4) was found to decrease as temperature rose from 28 to 32 °C. Values of two other stoichiometric parameters, i.e. the growth yield of heterotrophic organisms (Y H) and PAOs (Y PAO), were high at both temperatures. These calibrated parameters imply that the extremely active PAOs of the study were able to store PHA, store polyphosphate and even utilize PHA for cell growth. Besides, the parameters do not follow the Arrhenius correlation due to the previously reported unique microbial clade at 28 and 32 °C, which actively performs EBPR at high temperatures.

Matched MeSH terms: Glycogen/chemistry
Effects of sleeping with reduced carbohydrate availability on acute training responses

Lane SC, Camera DM, Lassiter DG, Areta JL, Bird SR, Yeo WK, et al.

J Appl Physiol (1985), 2015 Sep 15;119(6):643-55.
PMID: 26112242 DOI: 10.1152/japplphysiol.00857.2014

We determined the effects of "periodized nutrition" on skeletal muscle and whole body responses to a bout of prolonged exercise the following morning. Seven cyclists completed two trials receiving isoenergetic diets differing in the timing of ingestion: they consumed either 8 g/kg body mass (BM) of carbohydrate (CHO) before undertaking an evening session of high-intensity training (HIT) and slept without eating (FASTED), or consumed 4 g/kg BM of CHO before HIT, then 4 g/kg BM of CHO before sleeping (FED). The next morning subjects completed 2 h of cycling (120SS) while overnight fasted. Muscle biopsies were taken on day 1 (D1) before and 2 h after HIT and on day 2 (D2) pre-, post-, and 4 h after 120SS. Muscle [glycogen] was higher in FED at all times post-HIT (P < 0.001). The cycling bouts increased PGC1α mRNA and PDK4 mRNA (P < 0.01) in both trials, with PDK4 mRNA being elevated to a greater extent in FASTED (P < 0.05). Resting phosphorylation of AMPK(Thr172), p38MAPK(Thr180/Tyr182), and p-ACC(Ser79) (D2) was greater in FASTED (P < 0.05). Fat oxidation during 120SS was higher in FASTED (P = 0.01), coinciding with increases in ACC(Ser79) and CPT1 as well as mRNA expression of CD36 and FABP3 (P < 0.05). Methylation on the gene promoter for COX4I1 and FABP3 increased 4 h after 120SS in both trials, whereas methylation of the PPARδ promoter increased only in FASTED. We provide evidence for shifts in DNA methylation that correspond with inverse changes in transcription for metabolically adaptive genes, although delaying postexercise feeding failed to augment markers of mitochondrial biogenesis.

Matched MeSH terms: Glycogen/metabolism
Fulltext Primary malignant melanoma of vagina: the options of management

Ng, B.K., Lim, P.S., Ng, Y.L., Kew, T.Y., Abdul Kadir, A.K., Hatta, M.

Journal of Surgical Academia, 2014;4(1):63-66.
MyJurnal

Primary malignant melanoma of the vagina is rare but aggressive. Various treatment options include surgery and adjuvant therapy has been advocated but the outcome remained unpredictable. Standard treatment protocol is yet to be established. We report a case of 54-year-old, Para 4+1, with malignant melanoma of the vagina. She underwent wide local excision but the surgical margin was not clear of malignant cells, hence adjuvant radiotherapy was given. Combination chemotherapy was initiated subsequently as her disease disseminated. She succumbed later due to septicaemic shock. The treatment options for vaginal melanoma were reviewed.

Matched MeSH terms: Glycogen Storage Disease Type VI
Fulltext Anti-malarial and anti-inflammatory effects of Gleichenia truncata mediated through inhibition of GSK3β

Suhaini S, Liew SZ, Norhaniza J, Lee PC, Jualang G, Embi N, et al.

Trop Biomed, 2015 Sep;32(3):419-33.
PMID: 26695202 MyJurnal

Gleichenia truncata is a highland fern from the Gleicheniaceae family known for its traditional use among indigenous communities in Asia to treat fever. The scientific basis of its effect has yet to be documented. A yeast-based kinase assay conducted in our laboratory revealed that crude methanolic extract (CME) of G. truncata exhibited glycogen synthase kinase-3 (GSK3)-inhibitory activity. GSK3β is now recognized to have a pivotal role in the regulation of inflammatory response during bacterial infections. We have also previously shown that lithium chloride (LiCl), a GSK3 inhibitor suppressed development of Plasmodium berghei in a murine model of malarial infection. The present study is aimed at evaluating G. truncata for its anti-malarial and anti-inflammatory effects using in vivo malarial and melioidosis infection models respectively. In a four-day suppressive test, intraperitoneal injections of up to 250 mg/kg body weight (bw) G. truncata CME into P.berghei-infected mice suppressed parasitaemia development by >60%. Intraperitoneal administration of 150 mg/kg bw G. truncata CME into Burkholderia pseudomallei-infected mice improved survivability by 44%. G. truncata CME lowered levels of pro-inflammatory cytokines (TNF-α, IFN-γ) in serum and organs of B. pseudomallei-infected mice. In both infections, increased phosphorylations (Ser9) of GSK3β were detected in organ samples of animals administered with G. truncata CME compared to controls. Taken together, results from this study strongly suggest that the anti-malarial and anti-inflammatory effects elicited by G. truncata in part were mediated through inhibition of GSK3β. The findings provide scientific basis for the ethnomedicinal use of this fern to treat inflammation-associated symptoms.

Matched MeSH terms: Glycogen Synthase Kinase 3/antagonists & inhibitors*
Fulltext Regulatory role of GSK3β in the activation of NF-κB and modulation of cytokine levels in Burkholderia pseudomallei-infected PBMC isolated from streptozotocin-induced diabetic animals

Maniam P, Nurul Aiezzah Z, Mohamed R, Embi N, Hasidah MS

Trop Biomed, 2015 Mar;32(1):36-48.
PMID: 25801253

Increased susceptibility of diabetics to melioidosis, a disease caused by the Burkholderia pseudomallei bacterium is believed to be attributed to dysfunction of the innate immune system. However, the underlying mechanism of the innate susceptibility is not well-understood. Glycogen synthase kinase-3β (GSK3β) plays an important role in the innate inflammatory response caused by bacterial pathogens. The present study was conducted to investigate the effects of GSK3β inhibition by LiCl on levels of pro- and anti-inflammatory cytokines; and the activity of transcription factor NF-κB in B. pseudomallei-infected peripheral blood mononuclear cells (PBMC) derived from diabetic-induced and normal Sprague Dawley rats. In addition, the effects of LiCl on intracellular bacterial counts were also investigated. Infection of PBMC from diabetic and normal rats with B. pseudomallei resulted in elevated levels of cytokines (TNF-α, IL-12 and IL-10) and phosphorylation of NF-κB in both cell types. Intracellular bacterial counts decreased with time in both cell types during infection. However bacterial clearance was less prominent in diabetic PBMC. Burkholderia pseudomallei infection also caused inactivation (Ser9 phosphorylation) of GSK3β in normal PBMC, an effect absent in infected diabetic PBMC. Inhibition of GSK3β by LiCl lowered the levels of pro-inflammatory cytokines (TNF-α and IL-12) in both normal and diabetic PBMC. Similarly, phosphorylated NF- κB (pNF-κB) levels in both cell types were decreased with LiCl treatment. Also, LiCl was able to significantly decrease the intracellular bacterial count in normal as well as diabetic PBMC. Interestingly, the levels of anti-inflammatory cytokine IL-10 in both normal and diabetic PBMC were further elevated with GSK3β inhibition. More importantly, GSK3β in infected diabetic PBMC was inactivated as in their non-diabetic counterparts upon LiCl treatment. Taken together, our results suggest that inhibition of dysregulated GSK3β in diabetic PBMC resulted in the inactivation of NF-κB and modulation of inflammatory cytokine levels. This is evidence that dysregulation of GSK3β is a contributing factor in the molecular basis of innate dysfunction and susceptibility of diabetic host to melioidosis infection.

Matched MeSH terms: Glycogen Synthase Kinase 3/antagonists & inhibitors; Glycogen Synthase Kinase 3/metabolism*

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