MyMedR

Displaying publications 21 - 40 of 78 in total

Abstract:

Sort:

Fulltext Glycogenic hepatopathy in children with poorly controlled type 1 diabetes mellitus

Abu NA, Lim CB, Nor NSM

Clin Pediatr Endocrinol, 2021;30(2):93-97.
PMID: 33867669 DOI: 10.1297/cpe.30.93

Mauriac syndrome is a rare and underdiagnosed complication of type 1 diabetes mellitus (T1DM). It is characterized by growth retardation, delayed puberty, Cushingoid features, hepatomegaly, and increased transaminase levels. The term glycogenic hepatopathy has been used to describe patients with poorly controlled T1DM and glycogen overload in the hepatocytes but without all the features of Mauriac syndrome. Although rare, glycogenic hepatopathy is reported to be the main cause of hepatomegaly in young patients with T1DM. We report two cases of glycogenic hepatopathy in children with poorly controlled T1DM. Both children had hepatomegaly, elevated liver enzyme levels, and elevated lactate levels. A liver biopsy confirmed the diagnosis of glycogenic hepatopathy in both patients. In conclusion, hepatomegaly with elevated liver enzymes, negative infective and metabolic screenings and persistently elevated plasma lactate levels should raise the suspicion of glycogenic hepatopathy in poorly controlled T1DM. Early diagnosis and improvement in glycemic control are the mainstays of treatment, which can prevent long-term complications.

Matched MeSH terms: Glycogen
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
Metabolic utilization of human osteoblast cell line hFOB 1.19 under normoxic and hypoxic conditions: A phenotypic microarray analysis

Cui YC, Qiu YS, Wu Q, Bu G, Peli A, Teh SW, et al.

Exp Biol Med (Maywood), 2021 May;246(10):1177-1183.
PMID: 33535809 DOI: 10.1177/1535370220985468

Osteoblasts play an important role in bone regeneration and repair. The hypoxia condition in bone occurs when bone undergoes fracture, and this will trigger a series of biochemical and mechanical changes to enable bone repair. Hence, it is interesting to observe the metabolites and metabolism changes when osteoblasts are exposed to hypoxic condition. This study has looked into the response of human osteoblast hFOB 1.19 under normoxic and hypoxic conditions by observing the cell growth and utilization of metabolites via Phenotype MicroArrays™ under these two different oxygen concentrations. The cell growth of hFOB 1.19 under hypoxic condition showed better growth compared to hFOB 1.19 under normal condition. In this study, osteoblast used glycolysis as the main pathway to produce energy as hFOB 1.19 in both hypoxic and normoxic conditions showed cell growth in well containing dextrin, glycogen, maltotriose, D-maltose, D-glucose-6-phospate, D-glucose, D-mannose, D-Turanose, D-fructose-6-phosphate, D-galactose, uridine, adenosine, inosine and α-keto-glutaric acid. In hypoxia, the cells have utilized additional metabolites such as α-D-glucose-1-phosphate and D-fructose, indicating possible activation of glycogen synthesis and glycogenolysis to metabolize α-D-glucose-1-phosphate. Meanwhile, during normoxia, D-L-α-glycerol phosphate was used, and this implies that the osteoblast may use glycerol-3-phosphate shuttle and oxidative phosphorylation to metabolize glycerol-3-phosphate.

Matched MeSH terms: Glycogen; Glycogenolysis
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
Exogenous Abscisic Acid Supplementation at Early Stationary Growth Phase Triggers Changes in the Regulation of Fatty Acid Biosynthesis in Chlorella vulgaris UMT-M1

Norlina R, Norashikin MN, Loh SH, Aziz A, Cha TS

Appl Biochem Biotechnol, 2020 Aug;191(4):1653-1669.
PMID: 32198601 DOI: 10.1007/s12010-020-03312-y

Abscisic acid (ABA) has been known to exist in a microalgal system and serves as one of the chemical stimuli in various biological pathways. Nonetheless, the involvement of ABA in fatty acid biosynthesis, particularly at the transcription level in microalgae is poorly understood. The objective of this study was to determine the effects of exogenous ABA on growth, total oil content, fatty acid composition, and the expression level of beta ketoacyl-ACP synthase I (KAS I) and omega-3 fatty acid desaturase (ω-3 FAD) genes in Chlorella vulgaris UMT-M1. ABA was applied to early stationary C. vulgaris cultures at concentrations of 0, 10, 20, and 80 μM for 48 h. The results showed that ABA significantly increased biomass production and total oil content. The increment of palmitic (C16:0) and stearic (C18:0) acids was coupled by decrement in linoleic (C18:2) and α-linolenic (C18:3n3) acids. Both KAS I and ω-3 FAD gene expression were downregulated, which was negatively correlated to saturated fatty acid (SFAs), but positively correlated to polyunsaturated fatty acid (PUFA) accumulations. Further analysis of both KAS I and ω-3 FAD promoters revealed the presence of multiple ABA-responsive elements (ABREs) in addition to other phytohormone-responsive elements. However, the role of these phytohormone-responsive elements in regulating KAS I and ω-3 FAD gene expression still remains elusive. This revelation might suggest that phytohormone-responsive gene regulation in C. vulgaris and microalgae as a whole might diverge from higher plants which deserve further scientific research to elucidate its functional roles.

Matched MeSH terms: Glycogen Synthase
Fulltext Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia

Abdul Wahab SA, Yakob Y, Mohd Khalid MKN, Ali N, Leong HY, Ngu LH

Genet Res (Camb), 2022;2022:5870092.
PMID: 36160031 DOI: 10.1155/2022/5870092

BACKGROUND: Glycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6Pase); an enzyme that catalyses the hydrolysis of glucose-6-phosphate (G6P) to phosphate and glucose.
OBJECTIVE: To elaborate on the clinical findings, biochemical data, molecular genetic analysis, and short-term prognosis of 13 GSD1a patients in Malaysia.
METHODS: The information about 13 clinically classified GSD1a patients was retrospectively studied. The G6PC mutation analysis was performed by PCR-DNA sequencing.
RESULTS: Patients were presented with hepatomegaly (92%), hypoglycaemia (38%), poor weight gain (23%), and short stature (15%). Mutation analysis revealed nine heterozygous mutations; eight previously reported mutations (c.155 A > T, c.209 G > A, c.226 A > T, c.248 G > A, c.648 G > T, c.706 T > A, c.1022 T > A, c.262delG) and a novel mutation (c.325 T > C). The most common mutation found in Malaysian patients was c.648 G > T in ten patients (77%) of mostly Malay ethnicity, followed by c.248 G > A in 4 patients of Chinese ethnicity (30%). A novel missense mutation (c.325 T > C) was predicted to be disease-causing by various in silico software.
CONCLUSIONS: The establishment of G6PC molecular genetic testing will enable the detection of presymptomatic patients, assisting in genetic counselling while avoiding the invasive methods of liver biopsy.

Matched MeSH terms: Glycogen Storage Disease Type I
Fulltext Phyllanthus Suppresses Prostate Cancer Cell, PC-3, Proliferation and Induces Apoptosis through Multiple Signalling Pathways (MAPKs, PI3K/Akt, NFκB, and Hypoxia)

Tang YQ, Jaganath I, Manikam R, Sekaran SD

Evid Based Complement Alternat Med, 2013;2013:609581.
PMID: 23690850 DOI: 10.1155/2013/609581

Phyllanthus is a traditional medicinal plant that has been found to have antihepatitis, antibacterial, and anticancer properties. The present studies were to investigate the in vitro molecular mechanisms of anticancer effects of Phyllanthus (P. amarus, P. niruri, P. urinaria, and P. watsonii) plant extracts in human prostate adenocarcinoma. The cancer ten-pathway reporter array was performed and revealed that the expression of six pathway reporters were significantly decreased (Wnt, NFκB, Myc/Max, hypoxia, MAPK/ERK, and MAPK/JNK) in PC-3 cells after treatment with Phyllanthus extracts. Western blot was conducted and identified several signalling molecules that were affected in the signalling pathways including pan-Ras, c-Raf, RSK, Elk1, c-Jun, JNK1/2, p38 MAPK, c-myc, DSH, β-catenin, Akt, HIF-1α, GSK3β, NFκB p50 and p52, Bcl-2, Bax, and VEGF, in treated PC-3 cells. A proteomics-based approach, 2D gel electrophoresis, was performed, and mass spectrometry (MS/MS) results revealed that there were 72 differentially expressed proteins identified in treated PC-3 cells and were involved in tumour cell adhesion, apoptosis, glycogenesis and glycolysis, metastasis, angiogenesis, and protein synthesis and energy metabolism. Overall, these findings suggest that Phyllanthus can interfere with multiple signalling cascades involved in tumorigenesis and be used as a potential therapeutic candidate for treatment of cancer.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta
Scoparia dulcis (SDF7) endowed with glucose uptake properties on L6 myotubes compared insulin

Beh JE, Latip J, Abdullah MP, Ismail A, Hamid M

J Ethnopharmacol, 2010 May 4;129(1):23-33.
PMID: 20193753 DOI: 10.1016/j.jep.2010.02.009

Insulin stimulates glucose uptake and promotes the translocation of glucose transporter 4 (Glut 4) to the plasma membrane on L6 myotubes. The aim of this study is to investigate affect of Scoparia dulcis Linn water extracts on glucose uptake activity and the Glut 4 translocation components (i.e., IRS-1, PI 3-kinase, PKB/Akt2, PKC and TC 10) in L6 myotubes compared to insulin.

Matched MeSH terms: Glycogen/metabolism
Mitochondrial disorder, diabetes mellitus, and findings in three muscles, including the heart

Bhattacharjee M, Venugopal B, Wong KT, Goto YI, Bhattacharjee MB

Ultrastruct Pathol, 2006 Nov-Dec;30(6):481-7.
PMID: 17183762

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.

Matched MeSH terms: Glycogen/ultrastructure
Strategies adopted by the mudskipper Boleophthalmus boddaerti to survive sulfide exposure in normoxia or hypoxia

Ip YK, Kuah SS, Chew SF

Physiol Biochem Zool, 2004 Sep-Oct;77(5):824-37.
PMID: 15547800

The effects of sulfide on the energy metabolism of Boleophthalmus boddaerti in normoxia and hypoxia were examined. The 24-, 48-, and 96-h LC50 values of sulfide for B. boddaerti with body weight ranging from 11.6 to 14.2 g were 0.786, 0.567, and 0.467 mM, respectively. The tolerance of B. boddaerti to sulfide was not due to the presence of a sulfide-insensitive cytochrome c oxidase. There was no accumulation of lactate in the muscle and liver of specimens exposed to sulfide in normoxia. In addition, the levels of ATP, AMP, and energy charge in both the muscle and the liver were unaffected. These results indicate that B. boddaerti was able to sustain the energy supply required for its metabolic needs via mainly aerobic respiration when exposed to sulfide (up to 0.4 mM) in normoxia. Exposure of B. boddaerti simultaneously to hypoxia and 0.2 mM sulfide for 48 h resulted in decreases in the ATP levels in the muscle and liver. However, the energy charge in both tissues remained unchanged, and the level of lactate accumulated in the muscle was too low to have any major contribution to the energy budget of the fish. Our results reveal that B. boddaerti possesses inducible mechanisms to detoxify sulfide in an ample supply or a lack of O2. In normoxia, it detoxified sulfide to sulfate, sulfite, and thiosulfate. There were significant increases in the activities of sulfide oxidase in the muscle and liver of specimens exposed to sulfide, with that in the liver being >13-fold higher than that in the muscle. However, in hypoxia, sulfide oxidase activity in the liver was suppressed in response to environmental sulfide. In such conditions, there were significant increases in the activities of sulfane sulfur-forming enzyme(s) in the muscle and liver that were not observed in specimens exposed to sulfide in normoxia. Correspondingly, there were no changes in the levels of sulfate or sulfite in the muscle or liver. Instead, B. boddaerti detoxified sulfide mainly to sulfane sulfur in hypoxia. In conclusion, B. boddaerti was able to activate different mechanisms to detoxify sulfide, producing different types of detoxification products in normoxia and hypoxia.

Matched MeSH terms: Glycogen/metabolism
Influence of gas stunning and halal slaughter (no stunning) on rabbits welfare indicators and meat quality

Nakyinsige K, Sazili AQ, Zulkifli I, Goh YM, Abu Bakar F, Sabow AB

Meat Sci, 2014 Dec;98(4):701-8.
PMID: 25089797 DOI: 10.1016/j.meatsci.2014.05.017

This study assessed the effect of gas stunning which has not been conducted until now in comparison with slaughter without stunning on the welfare and meat quality of rabbits. Eighty male New Zealand White rabbits were divided into two groups of 40 animals and subjected to either halal slaughter without stunning (HS) or gas stunning using 61.4% CO2, 20.3% oxygen and 18.3 % nitrogen (GS). Analysis of the sticking blood revealed that both slaughter procedures caused a substantial increase in the levels of catecholamines, hypercalcemia, hyperglycemia, lactic acidemia and an increase in enzyme activities. The ultimate pH of the Longissimus lumborum muscle did not differ between treatments. GS exhibited higher lightness and cooking loss, and lower glycogen and MFI than HS. This indicates that both GS and HS can be significant stressors although the amount of stress may be below the threshold to negatively affect rabbit meat quality.

Matched MeSH terms: Glycogen/metabolism
GSK-3beta phosphorylation and alteration of beta-catenin in hepatocellular carcinoma

Ban KC, Singh H, Krishnan R, Seow HF

Cancer Lett, 2003 Sep 25;199(2):201-8.
PMID: 12969793

The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p=0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p<0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure.

Matched MeSH terms: Glycogen Synthase Kinase 3/metabolism*
Fulltext Lithium chloride enhances serotonin induced calcium activity in EGFP-GnIH neurons

Teo CH, Soga T, Parhar I

Sci Rep, 2020 08 17;10(1):13876.
PMID: 32807874 DOI: 10.1038/s41598-020-70710-x

Neurons synthesizing gonadotropin-inhibitory hormone (GnIH) have been implicated in the control of reproduction, food intake and stress. Serotonin (5-HT) receptors have been shown in GnIH neurons; however, their functional role in the regulation of GnIH neurons remains to be elucidated. In this study, we measured intracellular calcium ion levels following 5-HT treatment to hypothalamic primary cultures of enhanced fluorescent green protein-tagged GnIH (EGFP-GnIH) neurons from Wistar rat pups of mixed sex. Three days after initial seeding of the primary cultures, the test groups were pre-treated with lithium chloride to selectively inhibit glycogen synthase kinase 3 beta to promote intracellular calcium levels, whereas the control groups received culture medium with no lithium chloride treatment. 24 h later, the cultures were incubated with rhodamine-2AM (rhod-2AM) calcium indicator dye for one hour prior to imaging. 5-HT was added to the culture dishes 5 min after commencement of imaging. Analysis of intracellular calcium levels in EGFP-GnIH neurons showed that pre-treatment with lithium chloride before 5-HT treatment resulted in significant increase in intracellular calcium levels, two times higher than the baseline. This suggests that lithium chloride enhances the responsiveness of GnIH neurons to 5-HT.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/antagonists & inhibitors
Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training

Mohktar RA, Montgomery MK, Murphy RM, Watt MJ

Am J Physiol Endocrinol Metab, 2016 07 01;311(1):E128-37.
PMID: 27189934 DOI: 10.1152/ajpendo.00084.2016

Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training.

Matched MeSH terms: Glycogen/metabolism
Fulltext Suppression of Plasmodium berghei parasitemia by LiCl in an animal infection model

Nurul Aiezzah Z, Noor E, Hasidah MS

Trop Biomed, 2010 Dec;27(3):624-31.
PMID: 21399604 MyJurnal

Malaria, caused by the Plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. The search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant Plasmodium falciparum strains. Protein kinases such as mitogen-activated protein kinase (MAPK), MAPK kinase, cyclin-dependent kinase (CDK) and glycogen synthase kinase- 3(GSK-3) of parasitic protozoa are potential drug targets. GSK-3 is an enzyme that plays a vital role in multiple cellular processes, and has been linked to pathogenesis of several diseases such as type II diabetes and Alzheimer's disease. In the present study, the antiplasmodial property of LiCl, a known GSK-3 inhibitor, was evaluated in vivo for its antimalarial effect against mice infected with Plasmodium berghei. Infected ICR mice were intraperitoneally administered with LiCl for four consecutive days before (prophylactic test) and after (suppressive test) inoculation of P. berghei-parasitised erythrocytes. Results from the suppressive test (post-infection LiCl treatment) showed inhibition of erythrocytic parasitemia development by 62.06%, 85.67% and 85.18% as compared to nontreated controls for the 100 mg/kg, 300 mg/kg and 600 mg/kg dosages respectively. Both 300 mg/kg and 600 mg/kg LiCl showed similar significant (P<0.05) suppressive values to that obtained with chloroquine-treated mice (86% suppression). The prophylactic test indicated a significantly (P<0.05) high protective effect on mice pre-treated with LiCl with suppression levels relatively comparable to chloroquine (84.07% and 86.26% suppression for the 300 mg/kg and 600 mg/kg LiCl dosages respectively versus 92.86% suppression by chloroquine). In both the suppressive and prophylactic tests, LiCl-treated animals survived longer than their non-treated counterparts. Mortality of the non-treated mice was 100% within 6 to 7 days of parasite inoculation whereas mice administered with LiCl survived beyond 9 days. Healthy non-infected mice administered with 600 mg/ kg LiCl for four consecutive days also showed decreased mortality compared to animals receiving lower doses of LiCl; three of the seven mice intraperitoneally injected with the former dose of LiCl did not survive more than 24 h after administration of LiCl whereas animals given the lower LiCl doses survived beyond four days of LiCl administration. To date, no direct evidence of anti-malarial activity in vivo or in vitro has been reported for LiCl. Evidence of anti-plasmodial activity of lithium in a mouse infection model is presented in this study.

Matched MeSH terms: Glycogen Synthase Kinase 3/antagonists & inhibitors
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
Anti-malarial and cytokine-modulating effects of andrographolide in a murine model of malarial infection

Hassan WRM, Basir R, Ali AH, Embi N, Sidek HM

Trop Biomed, 2019 Sep 01;36(3):776-791.
PMID: 33597499

Malarial pathogenesis involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. The ubiquitous serine/threonine kinase, glycogen synthase kinase3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Andrographolide, a bioactive compound in Andrographis paniculata, displays GSK3- inhibitory effects. A previous study elsewhere has shown that this compound has antimalarial activity but the molecular basis of its action is yet to be elucidated. Here we aimed to study the anti-malarial activity of andrographolide in a murine model of malarial infection to investigate whether its mechanism of action involves cytokine modulation and inhibition of GSK3β. Andrographolide showed strong and selective anti-plasmodial activity (IC50 = 13.70±0.71 µM; SI = 30.43) when tested against cultures of P. falciparum 3D7. Intraperitoneal administration of andrographolide (5 mg/kg body weight (bw)) into P. berghei NK65-infected ICR mice resulted in chemo-suppression of 60.17±2.12%, and significantly (P<0.05) improved median survival time of infected mice compared to nontreated control. In addition, andrographolide treatment significantly (P<0.05) decreased the level of serum pro-inflammatory cytokine, IFN-γ (1.4-fold) whilst the anti-inflammatory cytokines, IL-10 and IL-4 were increased 2.3- and 2.6-fold respectively. Western blot analyses revealed that andrographolide treatment of P. berghei NK65-infected mice resulted in an increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Andrographolide administration also decreased the levels of phosphorylated NF-κB p65 (Ser536) and phosphorylated Akt (Ser473) in liver of malaria- infected animals. Taken together, our findings demonstrate that the cytokine-modulating effect of andrographolide in experimental malarial infection involves at least in part inhibition of NF-κB activation as a consequence of GSK3β inhibition. Based on its cytokine-modulating effects, andrographolide is thus a plausible candidate for adjunctive therapy in malaria subject to clinical evaluations.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/antagonists & inhibitors
The combined effect of hypoxia and nutritional status on metabolic and ionoregulatory responses of common carp (Cyprinus carpio)

Moyson S, Liew HJ, Diricx M, Sinha AK, Blust R, De Boeck G

Comp Biochem Physiol A Mol Integr Physiol, 2015 Jan;179:133-43.
PMID: 25263807 DOI: 10.1016/j.cbpa.2014.09.017

In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasted fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels. Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasted fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasted fish transiently increased Na(+)/K(+)-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.

Matched MeSH terms: Glycogen/metabolism
Positive correlation between overexpression of phospho-BAD with phosphorylated Akt at serine 473 but not threonine 308 in colorectal carcinoma

Khor TO, Gul YA, Ithnin H, Seow HF

Cancer Lett, 2004 Jul 16;210(2):139-50.
PMID: 15183529

The enhancement of cell proliferation and promotion of cell survival via the inhibition of apoptosis is thought to be the key to the initiation and progression of cancers. The phosphatidylinositol-3 kinase (PI3K)/Akt is an important survival signal pathway that has been shown to be crucial in the regulation of balance between pro-apoptotic and survival (anti-apoptotic) signal. In this study, the expression of phosphorylated Akt at Thr308 and Ser473, BCL-2-antagonist of cell death (BAD) at Ser136 and glycogen synthase kinase-3beta (GSK-3beta) at Ser9 in 47 paraffin-embedded human colorectal carcinoma (CRC) tissues were determined by immunohistochemical staining in order to dissect the alterations in the signal transduction pathways in CRC. Our results showed that there was a significant increase in the expression of these biomolecules in CRC tissues compared to the apparently normal adjacent tissues. The frequency of increased expression in tumor colonic mucosa were as follows: p-Akt1/2/3 (Thr308) = 16/47 (34%); p-Akt1 (Ser473) = 21/47 (44.7%); phospho-BAD (p-BAD) Ser136 = 27/47 (57.4%) and phospho-GSK-3beta (p-GSK-3beta) = 21/47 (44.7%). Analysis of the total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score found that there was a statistically significant relationship with each other. A statistically significant positive linear relationship was found between total p-Akt (Ser473) score and total p-GSK-3beta (Ser9) score as well as with total p-BAD (Ser136) score. On the other hand, total p-Akt1/2/3 (Thr308) scores had a statistically significant positive linear relationship with p-GSK-3beta (Ser9) only. The Akt targets, p-GSK-3beta (Ser9) and p-BAD (Ser136) were positively correlated to each other. There was no significant correlation between clinico-pathological data with total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score except for age. The total scores of p-GSK-3beta were found to be higher in patients in the age group of greater than 60. This is the first report of p-Akt1/2/3 (Thr308) and p-BAD (Ser136) expression in primary colorectal tumor tissue. Our data further supports the role of PI3K/Akt signaling pathways in the pathogenesis of CRC and contributes to the identification of target molecules in the signal transduction pathway for cancer therapy.

Matched MeSH terms: Glycogen Synthase Kinase 3/biosynthesis*; Glycogen Synthase Kinase 3/genetics
Molecular process of glucose uptake and glycogen storage due to hamamelitannin via insulin signalling cascade in glucose metabolism

Issac PK, Guru A, Chandrakumar SS, Lite C, Saraswathi NT, Arasu MV, et al.

Mol Biol Rep, 2020 Sep;47(9):6727-6740.
PMID: 32809102 DOI: 10.1007/s11033-020-05728-5

Understanding the mechanism by which the exogenous biomolecule modulates the GLUT-4 signalling cascade along with the information on glucose metabolism is essential for finding solutions to increasing cases of diabetes and metabolic disease. This study aimed at investigating the effect of hamamelitannin on glycogen synthesis in an insulin resistance model using L6 myotubes. Glucose uptake was determined using 2-deoxy-D-[1-3H] glucose and glycogen synthesis were also estimated in L6 myotubes. The expression levels of key genes and proteins involved in the insulin-signaling pathway were determined using real-time PCR and western blot techniques. The cells treated with various concentrations of hamamelitannin (20 µM to 100 µM) for 24 h showed that, the exposure of hamamelitannin was not cytotoxic to L6 myotubes. Further the 2-deoxy-D-[1-3H] glucose uptake assay was carried out in the presence of wortmannin and Genistein inhibitor for studying the GLUT-4 dependent cell surface recruitment. Hamamelitannin exhibited anti-diabetic activity by displaying a significant increase in glucose uptake (125.1%) and glycogen storage (8.7 mM) in a dose-dependent manner. The optimum concentration evincing maximum activity was found to be 100 µm. In addition, the expression of key genes and proteins involved in the insulin signaling pathway was studied to be upregulated by hamamelitannin treatment. Western blot analysis confirmed the translocation of GLUT-4 protein from an intracellular pool to the plasma membrane. Therefore, it can be conceived that hamamelitannin exhibited an insulinomimetic effect by enhancing the glucose uptake and its further conversion into glycogen by regulating glucose metabolism.

Matched MeSH terms: Glycogen/metabolism*; Glycogen Synthase Kinase 3 beta/genetics; Glycogen Synthase Kinase 3 beta/metabolism

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links