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Fulltext Novel Inhibitory Effects of Glycyrrhizic Acid on the Accumulation of Advanced Glycation End Product and Its Receptor Expression

Cheng HS, Kong JM, Ng AX, Chan WK, Ton SH, Abdul Kadir K

Nat Prod Bioprospect, 2014 Dec;4(6):325-33.
PMID: 25369772 DOI: 10.1007/s13659-014-0044-0

Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice root, in the prevention of metabolic syndrome have been consistently reported while advanced glycation end products (AGE) and receptor for advanced glycation end product (RAGE) are the leading factors in the development of diabetes mellitus. The aim of this study was to investigate the effects of GA on the AGE-RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat models. Twenty four male Sprague-Dawley rats were randomly assigned into three groups for 4 weeks: (1) Group A, normal diet with standard rat chow; (2) Group B, HF/HS diet; (3) Group C, HF/HS diet and oral administration of 100 mg/kg GA per day. The results showed that HF/HS diet elevated the fasting blood glucose level and insulin resistance index which was prevented by GA supplementation. GA treatment significantly lowered the circulating AGE independent of its glucose-lowering effect. HF/HS diet also triggered RAGE upregulation in the abdominal muscles while GA administration downregulated RAGE expression in the abdominal muscles, aorta and subcutaneous adipose tissues. In conclusion, HF/HS diet could cause glucose intolerance, insulin resistance and upregulation of RAGE expression while GA ameliorated the metabolic dysregulation besides exhibiting inhibitory effects on the AGE-RAGE axis.
Fulltext Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

Eu CH, Lim WY, Ton SH, bin Abdul Kadir K

Lipids Health Dis, 2010;9:81.
PMID: 20670429 DOI: 10.1186/1476-511X-9-81

The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL), an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state.
Adding biphasic insulin aspart 30 once or twice daily is more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes

Bebakar WM, Chow CC, Kadir KA, Suwanwalaikorn S, Vaz JA, Bech OM, et al.

Diabetes Obes Metab, 2007 Sep;9(5):724-32.
PMID: 17593237 DOI: 10.1111/j.1463-1326.2007.00743.x

Aim: To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy.

Methods: This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling.

Results: Significantly greater reductions in HbA(1c) over Weeks 0-13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0-26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major.

Conclusions: Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered.
Glycyrrhizic acid prevents high calorie diet-induced metabolic aberrations despite the suppression of peroxisome proliferator-activated receptor γ expression

Cheng HS, Yaw HP, Ton SH, Choy SM, Kong JM, Abdul Kadir K

Nutrition, 2016 Sep;32(9):995-1001.
PMID: 27130470 DOI: 10.1016/j.nut.2016.02.002

OBJECTIVE: To investigate the effects of glycyrrhizic acid supplementation on glucose and lipid metabolism in rodents consuming a high-fat, high-sucrose diet.
METHODS: Twenty-four male, 8-week old Sprague Dawley rats with an initial weight of 160 to 200 g were randomised into three groups (n = 6 for each group): groups A (standard rat chow), B (high-fat, high-sucrose diet), and C (high-fat, high-sucrose diet + 100 mg/kg/d of glycyrrhizic acid via oral administration). The rats were treated accordingly for 4 wk. Glycaemic parameters, lipid profile, stress hormones, and adiponectin levels were measured after the treatment. Relative gene expressions of peroxisome proliferator-activated receptor α and γ, lipoprotein lipase as well as gluconeogenic enzymatic activities in different tissues were also determined.
RESULTS: Consumption of high-fat, high-sucrose diet triggered hyperglycaemia, insulin resistance, and dyslipidemia, which were effectively attenuated by supplementation with glycyrrhizic acid. Glycyrrhizic acid supplementation also effectively reduced circulating adrenaline, alleviated gluconeogenic enzymes overactivity, and promoted the upregulation of lipoprotein lipase expression in the cardiomyocytes and skeletal muscles. A high calorie diet also triggered hypoadiponectinaemia and suppression of peroxisome proliferator-activated receptor γ expression, which did not improve with glycyrrhizic acid treatment.
CONCLUSION: Supplementation with glycyrrhizic acid could alleviate high calorie diet-induced glucose and lipid metabolic dysregulations by reducing circulatory stress hormones, normalizing gluconeogenic enzyme activities, and elevating muscular lipid uptake. The beneficial effects of these bioactivities outweighed the adverse effects caused by diet-induced repression of peroxisome proliferator-activated receptor γ expression, resulting in the maintenance of lipid and glucose homeostasis.
Skin prick test reactivity to foods in adult Malaysians with rhinitis

Gendeh BS, Murad S, Razi AM, Abdullah N, Mohamed AS, Kadir KA

Otolaryngol Head Neck Surg, 2000 May;122(5):758-62.
PMID: 10793361

The aim of the study was to determine the incidence of food and house dust mite (HDM) allergy in patients with nasal congestion and rhinorrhea attending the Otorhinolaryngology Clinic, National University of Malaysia, Kuala Lumpur. This was a prospective matched, controlled study of patients skin prick tested with commercial food and common aeroallergens. The participants were 148 Malaysian adults with symptoms of nasal congestion and rhinorrhea and 113 adult Malaysian control subjects without rhinitis symptoms. The skin prick test (SPT) was used to evaluate 11 foods common to the Malaysian diet and 3 HDM inhalants. Forty-eight percent of the patients with rhinitis had positive SPT results to foods, compared with 4.4% of control subjects (P < 0.05). The most commonly implicated foods were shrimp (48%) and rice (30%), which are common in the Malaysian diet. Seventy-two percent of rhinitis patients had positive SPT results to HDM, compared with 22.2% of control subjects (P < 0.05). Patients with rhinitis also had significantly more gastrointestinal problems than control subjects (P < 0.05). The incidences of HDM and food allergy are significantly greater in Malaysian adults with rhinitis symptoms than in control subjects without rhinitis. The effect of avoidance or immunotherapy awaits further study.
Study site: Otorhinolaryngology Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
High prevalence of thyroid function test abnormalities in chronic schizophrenia

Othman SS, Abdul Kadir K, Hassan J, Hong GK, Singh BB, Raman N

Aust N Z J Psychiatry, 1994 Dec;28(4):620-4.
PMID: 7794205

The thyroid status of 249 patients with chronic schizophrenia (males = 136, females = 113) with a median age of 36 years (range: 16 to 58 years) and a median duration of hospitalisation of 10 years (range: 1 to 30 years) was assessed. Thyroid antibodies (TAb) were found in 51 patients (20%). In female patients, 32 (28%) were TAb positive compared to 13% (n = 152, p = 0.01) in healthy female blood donors. In male patients, the prevalence of TAb was 14% compared to 7% (n = 449, p = 0.01) in healthy male blood donors. Of the 183 patients who had thyroid hormone measurements, 60% had normal test, 5% had elevated TSH and 17% had low TSH. The T4, FT41 and FT31 were significantly lower in those with low or high TSH (p < 0.001) compared to those with normal TSH. Of the 143 patients with normal TSH, 33 (23%) had low T3. In conclusion, there is a spectrum of thyroid function test abnormalities in chronic schizophrenia; this may be related to an abnormality in the central regulation of the hypothalamo-pituitary thyroid axis as well as at the peripheral level. However the association between chronic schizophrenia and the presence of thyroid antibodies, and the clinical relevance of these biochemical abnormalities, are still not clear.
Differential effect of adrenocorticosteroids on 11 beta-hydroxysteroid dehydrogenase bioactivity at the anterior pituitary and hypothalamus in rats

Idrus RB, Mohamad NB, Morat PB, Saim A, Abdul Kadir KB

Steroids, 1996 Aug;61(8):448-52.
PMID: 8870163

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.
Purified ingredient-based high-fat diet is superior to chow-based equivalent in the induction of metabolic syndrome

Cheng HS, Phang SCW, Ton SH, Abdul Kadir K, Tan JBL

J Food Biochem, 2019 02;43(2):e12717.
PMID: 31353646 DOI: 10.1111/jfbc.12717

The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.
Effect of tocotrienol on the activities of cytosolic glutathione-dependent enzymes in rats treated with 2-acetylaminofluorene

Shamaan NA, Wan Ngah WZ, Ibrahim R, Jarien Z, Top AG, Abdul Kadir K

Biochem Pharmacol, 1993 Apr 06;45(7):1517-9.
PMID: 8471073

The effect of tocotrienol on the activities of glutathione S-transferases (GSTs), glutathione reductase (GR) and glutathione peroxidase (GPx) in rats given 2-acetylaminofluorene (AAF) was investigated over a 20 week period. Liver and kidney GST and liver GR activities were significantly increased after AAF administration. Kidney GPx activities were significantly affected; activity assayed with cumene hydroperoxide (cu-OOH) was increased but activity assayed with H2O2 was reduced. Supplementation of the diet with tocotrienol in the AAF-treated rats reduced the increase in enzyme activities. Tocotrienol on its own had no effect on the enzyme activities.
Fulltext Vitamin E Levels in Ethnic Communities in Malaysia and Its Relation to Glucose Tolerance, Insulin Resistance and Advanced Glycation End Products: A Cross-Sectional Study

Chua GHI, Phang SCW, Wong YO, Ho LS, Palanisamy UD, Abdul Kadir K

Nutrients, 2020 Nov 27;12(12).
PMID: 33261162 DOI: 10.3390/nu12123659

Malaysian national morbidity surveys on diabetic prevalence have shown ethnical variation among prediabetic and diabetic populations. In our attempt to understand this variation, we studied the α-tocopherol, insulin resistance, β-cell function and receptor of advanced glycation end-products (RAGE) levels, as risk factors of type 2 diabetes, among the different ethnicities. In total, 299 subjects of Malay, Chinese, Indian and aboriginal Orang Asli (OA) heritage were recruited from urban and rural areas of Malaysia by stratified random sampling. Serum α-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) and insulin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In subjects with pre-diabetes, OAs had the highest α-tocopherol level, followed by Chinese and Malays (0.8938, 0.8564 and 0.6948 respectively; p < 0.05). In diabetic subjects, Malays had significantly higher RAGE levels compared to Chinese and Indians (5579.31, 3473.40 and 3279.52 pg/mL respectively, p = 0.001). Low α-tocopherol level (OR = 3.021, p < 0.05) and high insulin resistance (OR = 2.423, p < 0.05) were linked strongly to the development of pre-diabetes. Low β-cell function (OR = 5.657, p < 0.001) and high RAGE level (OR = 3.244, p < 0.05) were linked strongly to the development of diabetes from pre-diabetes. These factors might be involved in the development of diabetes, along with genetic and environmental factors.
Translation and Adaptation of the Diagnostic Criteria for Temporomandibular Disorders into the Malay Language: Psychometric Evaluation of Contents

Tahir MKAM, Kadir K, Apipi M, Ismail SM, Yusof ZYM, Yap AU

J Oral Facial Pain Headache, 2020 12 9;34(4):323-330.
PMID: 33290438 DOI: 10.11607/ofph.2624

AIMS: To develop the Malay DC/TMD through a formal cross-cultural adaptation (CCA) process for use in non-English speaking populations and to determine the reliability and validity of the Malay Graded Chronic Pain Scale (M-GCPS) and Malay Jaw Functional Limitation Scale (M-JFLS).
METHODS: The English DC/TMD was translated into the Malay language using the forward-backward translation procedures specified in the INfORM guideline. The initial Malay instrument was pre-tested, and any discrepancies were identified and reconciled before producing the final Malay DC/TMD. Psychometric properties of the M-GCPS and M-JFLS were evaluated using a convenience sample of 252 subjects and were assessed using internal consistency and test-retest reliability, as well as face, content, concurrent, and construct validity testing. Internal consistency was assessed using Cronbach's alpha, while test-retest reliability was examined using intraclass correlation coefficient (ICC). Concurrent and construct validity of both domains were performed using Spearman ρ correlation test. In addition, construct and discriminant validity were appraised using Kruskal-Wallis and Mann-Whitney U tests, respectively.
RESULTS: Cronbach's alpha values for the M-GCPS and M-JFLS were 0.95 and 0.97, respectively. The ICC was 0.98 for the M-GCPS and 0.99 for M-JFLS. The majority of the tested associations for both domains were found to be statistically significant, with good positive correlations.
CONCLUSION: The M-GCPS and M-JFLS were found to be reproducible and valid. The Malay DC/TMD shows potential for use among Malay-speaking adults.
Fulltext Apoptosis repressor with caspase recruitment domain (ARC) promotes bone regeneration of bone marrow-derived mesenchymal stem cells by activating Fgf-2/PI3K/Akt signaling

Hu L, Wang Y, Pan H, Kadir K, Wen J, Li S, et al.

Stem Cell Res Ther, 2021 03 16;12(1):185.
PMID: 33726822 DOI: 10.1186/s13287-021-02253-5

OBJECTIVES: This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).
MATERIALS AND METHODS: The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs.
RESULTS: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway.
CONCLUSIONS: The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.
Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats

Ngah WZ, Jarien Z, San MM, Marzuki A, Top GM, Shamaan NA, et al.

Am J Clin Nutr, 1991 04;53(4 Suppl):1076S-1081S.
PMID: 1672785 DOI: 10.1093/ajcn/53.4.1076S

The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis.
Psychometric properties of the Malay Fonseca Anamnestic Index for temporomandibular disorders

Yap AU, Apipi M, Ismail SM, Yusof ZYM, Kadir K

Cranio, 2022 Apr 06.
PMID: 35384792 DOI: 10.1080/08869634.2022.2059130

OBJECTIVE: This study translated/cross-culturally adapted the Fonseca Anamnestic Index (FAI) for temporomandibular disorders (TMDs) into Malay and psychometrically tested the Malay-FAI (FAI-M).
METHODS: The FAI-M was created according to international guidelines. Internal consistency/test-retest reliability were assessed with Cronbach's alpha/intra-class correlation (ICC) coefficients. Construct and convergent validity were appraised by relating the FAI-M to the Global Oral Health (GOH) questionnaire and Short-form Oral Health Impact Profile (S-OHIP) using Kruskal-Wallis and Spearman's rho correlation (α = 0.05).
RESULTS: Of the 243 participants enrolled, 54.7% (n = 133) had no TMDs, while TMDs were present in 45.3% (n = 110). The FAI-M presented very good internal consistency (α = 0.90) and test-retest reliability (ICC = 0.99). Theoretically predicted FAI-M score patterns matched the GOH categories, and strong correlations were discerned between FAI-M and S-OHIP (rs = 0.71).
CONCLUSION: The FAI-M exhibited good psychometric properties and can be applied in Malay-speaking populations.
Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome

Cheng HS, Ton SH, Phang SCW, Tan JBL, Abdul Kadir K

J Adv Res, 2017 Nov;8(6):743-752.
PMID: 29062573 DOI: 10.1016/j.jare.2017.10.002

The present study aimed to examine the effects of the types of high-calorie diets (high-fat and high-fat-high-sucrose diets) and two different developmental stages (post-weaning and young adult) on the induction of metabolic syndrome. Male, post-weaning and adult (3- and 8-week old, respectively) Sprague Dawley rats were given control, high-fat (60% kcal), and high-fat-high-sucrose (60% kcal fat + 30% sucrose water) diets for eight weeks (n = 6 to 7 per group). Physical, biochemical, and transcriptional changes as well as liver histology were noted. Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose, high density lipoprotein cholesterol, faster hypertension onset, but lower circulating advanced glycation end products compared to adult rats. This is accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR) α and γ in the liver and receptor for advanced glycation end products (RAGE) in the visceral adipose tissue. Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression. Adult rats on high-fat-high-sucrose diet merely became obese and hypertensive within the same treatment duration. Thus, it is more effective and less time-consuming to induce metabolic syndrome in male post-weaning rats with high-fat diet compared to young adult rats. As male rats were selectively included into the study, the results may not be generalisable to all post-weaning rats and further investigation on female rats is required.
Salivary biomarkers: Effective diagnostic tool for oral leukoplakia and oral squamous cell carcinoma

Liew YX, Kadir K, Phan CW, Leong KH, Kallarakkal TG, Tilakaratne WM

Oral Dis, 2024 Sep;30(6):3591-3599.
PMID: 38098264 DOI: 10.1111/odi.14835

OBJECTIVE: To identify potential salivary biomarkers for the diagnosis and monitoring of disease progression in oral squamous cell carcinoma and oral leukoplakia.
MATERIALS AND METHODS: An advance search from PubMed and Hindawi was performed with keywords; oral leukoplakia/oral squamous cell carcinoma, salivary biomarker and diagnosis/prognosis. An additional search of articles was done through a manual search from the Google Scholar database.
RESULTS: Twenty studies involving salivary biomarkers as diagnostic tools for oral squamous cell carcinoma and/or oral leukoplakia were identified. A narrative review was carried out.
CONCLUSION: Single or multiple salivary biomarkers reported by most studies have shown great potential as diagnostic tools for oral squamous cell carcinoma and oral leukoplakia. However, the validation of sensitivity and specificity should be carried out to ensure the accuracy of the biomarkers. Furthermore, a standardised method for saliva collection should be established to prevent variability in the expression of biomarkers.
Real-time eye lens dose monitoring during cerebral angiography procedures

Safari MJ, Wong JH, Kadir KA, Thorpe NK, Cutajar DL, Petasecca M, et al.

Eur Radiol, 2016 Jan;26(1):79-86.
PMID: 26002131 DOI: 10.1007/s00330-015-3818-9

OBJECTIVES: To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures.
METHODS: Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures.
RESULTS: The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions.
CONCLUSIONS: The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose.
KEY POINTS: Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.
Fulltext A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Koay YY, Tan GCJ, Phang SCW, Ho JI, Chuar PF, Ho LS, et al.

Nutrients, 2021 Jan 18;13(1).
PMID: 33477404 DOI: 10.3390/nu13010258

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.
Pleiotropic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in rats

Cheng HS, Goh BH, Phang SCW, Amanullah MM, Ton SH, Palanisamy UD, et al.

Nutrition, 2020 08 12;79-80:110973.
PMID: 32916379 DOI: 10.1016/j.nut.2020.110973

OBJECTIVES: Metabolic syndrome (MetS), a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. The aim of this study was to characterize the metabolic effects and possible mechanism of geraniin in rats with MetS induced by a high-fat diet (HFD).
METHODS: MetS was induced in Sprague Dawley rats on an HFD, followed by a daily oral gavage of geraniin (25 mg/kg) for 4 wk. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a control diet or an HFD and with rats with MetS treated with metformin on a daily basis (200 mg/kg).
RESULTS: The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes that were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrial genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects.
CONCLUSION: Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.
Fulltext The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial

Ng YT, Phang SCW, Tan GCJ, Ng EY, Botross Henien NP, M Palanisamy UD, et al.

Nutrients, 2020 May 23;12(5).
PMID: 32456230 DOI: 10.3390/nu12051522

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

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