Displaying publications 1 - 20 of 25 in total

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  1. Naomi R, Bt Hj Idrus R, Fauzi MB
    PMID: 32961877 DOI: 10.3390/ijerph17186803
    Cellulose is a naturally existing element in the plant's cell wall and in several bacteria. The unique characteristics of bacterial cellulose (BC), such as non-toxicity, biodegradability, hydrophilicity, and biocompatibility, together with the modifiable form of nanocellulose, or the integration with nanoparticles, such as nanosilver (AgNP), all for antibacterial effects, contributes to the extensive usage of BC in wound healing applications. Due to this, BC has gained much demand and attention for therapeutical usage over time, especially in the pharmaceutical industry when compared to plant cellulose (PC). This paper reviews the progress of related research based on in vitro, in vivo, and clinical trials, including the overall information concerning BC and PC production and its mechanisms in wound healing. The physicochemical differences between BC and PC have been clearly summarized in a comparison table. Meanwhile, the latest Food and Drug Administration (FDA) approved BC products in the biomedical field are thoroughly discussed with their applications. The paper concludes on the need for further investigations of BC in the future, in an attempt to make BC an essential wound dressing that has the ability to be marketable in the global marketplace.
  2. Naomi R, Ratanavaraporn J, Fauzi MB
    Materials (Basel), 2020 Jul 10;13(14).
    PMID: 32664418 DOI: 10.3390/ma13143097
    The use of hybridisation strategy in biomaterials technology provides a powerful synergistic effect as a functional matrix. Silk fibroin (SF) has been widely used for drug delivery, and collagen (Col) resembles the extracellular matrix (ECM). This systematic review was performed to scrutinise the outcome of hybrid Col and SF for cutaneous wound healing. This paper reviewed the progress of related research based on in vitro and in vivo studies and the influence of the physicochemical properties of the hybrid in wound healing. The results indicated the positive outcome of hybridising Col and SF for cutaneous wound healing. The hybridisation of these biomaterials exhibits an excellent moisturising property, perfectly interconnected structure, excellent water absorption and retention capacity, an acceptable range of biodegradability, and synergistic effects in cell viability. The in vitro and in vivo studies clearly showed a promising outcome in the acceleration of cutaneous wound healing using an SF and Col hybrid scaffold. The review of this study can be used to design an appropriate hybrid scaffold for cutaneous wound healing. Therefore, this systematic review recapitulated that the hybridisation of Col and SF promoted rapid cutaneous healing through immediate wound closure and reepithelisation, with no sign of adverse events. This paper concludes on the need for further investigations of the hybrid SF and Col in the future to ensure that the hybrid biomaterials are well-suited for human skin.
  3. Naomi R, Ridzuan PM, Bahari H
    Polymers (Basel), 2021 Aug 09;13(16).
    PMID: 34451183 DOI: 10.3390/polym13162642
    Collagen type I (Col-I) is unique due to its high biocompatibility in human tissue. Despite its availability from various sources, Col-I naturally mimics the extracellular matrix (ECM) and generally makes up the larger protein component (90%) in vasculature, skin, tendon bone, and other tissue. The acceptable physicochemical properties of native Col-I further enhance the incorporation of Col-I in various fields, including pharmaceutical, cosmeceutical, regenerative medicine, and clinical. This review aims to discuss Col-I, covering the structure, various sources of availability, native collagen synthesis, current extraction methods, physicochemical characteristics, applications in various fields, and biomarkers. The review is intended to provide specific information on Col-I currently available, going back five years. This is expected to provide a helping hand for researchers who are concerned about any development on collagen-based products particularly for therapeutic fields.
  4. Naomi R, Ardhani R, Hafiyyah OA, Fauzi MB
    Polymers (Basel), 2020 Sep 13;12(9).
    PMID: 32933133 DOI: 10.3390/polym12092081
    Collagen (Col) is a naturally available material and is widely used in the tissue engineering and medical field owing to its high biocompatibility and malleability. Promising results on the use of Col were observed in the periodontal application and many attempts have been carried out to inculcate Col for gingival recession (GR). Col is found to be an excellent provisional bioscaffold for the current treatment in GR. Therefore, the aim of this paper is to scrutinize an overview of the reported Col effect focusing on in vitro, in vivo, and clinical trials in GR application. A comprehensive literature search was performed using EBSCOhost, Science Direct, Springer Link, and Medline & Ovid databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) collagen OR scaffold OR hybrid scaffold OR biomaterial AND (2) gingiva recession OR tissue regeneration OR dental tissue OR healing mechanism OR gingiva. Only articles published from 2015 onwards were selected for further analysis. This review includes the physicochemical properties of Col scaffold and the outcome for GR. The comprehensive literature search retrieved a total of 3077 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 15 articles were chosen for further review. The results from these articles indicated that Col promoted gingival tissue regeneration for GR healing. Therefore, this systematic review recapitulated that Col enhances regeneration of gingival tissue either through a slow or rapid process with no sign of cytotoxicity or adverse effect.
  5. Wang X, Walker A, Revez JA, Ni G, Adams MJ, McIntosh AM, et al.
    Am J Hum Genet, 2023 Jul 06;110(7):1207-1215.
    PMID: 37379836 DOI: 10.1016/j.ajhg.2023.06.006
    In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2, the proportion of total phenotypic variances attributable to all common SNPs) is the theoretical upper limit of the out-of-sample prediction R2. However, in real data analyses R2 has been reported to exceed hSNP2, which occurs in parallel with the observation that hSNP2 estimates tend to decline as the number of cohorts being meta-analyzed increases. Here, we quantify why and when these observations are expected. Using theory and simulation, we show that if heterogeneities in cohort-specific hSNP2 exist, or if genetic correlations between cohorts are less than one, hSNP2 estimates can decrease as the number of cohorts being meta-analyzed increases. We derive conditions when the out-of-sample prediction R2 will be greater than hSNP2 and show the validity of our derivations with real data from a binary trait (major depression) and a continuous trait (educational attainment). Our research calls for a better approach to integrating information from multiple cohorts to address issues of between-cohort heterogeneity.
  6. Salleh A, Naomi R, Utami ND, Mohammad AW, Mahmoudi E, Mustafa N, et al.
    Nanomaterials (Basel), 2020 Aug 09;10(8).
    PMID: 32784939 DOI: 10.3390/nano10081566
    Rapid development of nanotechnology has been in high demand, especially for silver nanoparticles (AgNPs) since they have been proven to be useful in various fields such as medicine, textiles, and household appliances. AgNPs are very important because of their unique physicochemical and antimicrobial properties, with a myriad of activities that are applicable in various fields, including wound care management. This review aimed to elucidate the underlying mechanisms of AgNPs that are responsible for their antiviral properties and their antibacterial activity towards the microorganisms. AgNPs can be synthesized through three different methods-physical, chemical, and biological synthesis-as indicated in this review. The applications and limitations of the AgNPs such as their cytotoxicity towards humans and the environment, will be discussed. Based on the literature search obtained, the properties of AgNPs scrutinizing the antibacterial or antiviral effect shown different interaction towards bacteria which dependent on the synthesis processes followed by the morphological structure of AgNPs.
  7. Naomi R, Embong H, Othman F, Ghazi HF, Maruthey N, Bahari H
    Nutrients, 2021 Dec 22;14(1).
    PMID: 35010895 DOI: 10.3390/nu14010020
    Alzheimer's disease (AD) is the most common form of neurodegenerative disorders affecting mostly the elderly. It is characterized by the presence of Aβ and neurofibrillary tangles (NFT), resulting in cognitive and memory impairment. Research shows that alteration in gut microbial diversity and defects in gut brain axis are linked to AD. Probiotics are known to be one of the best preventative measures against cognitive decline in AD. Numerous in vivo trials and recent clinical trials have proven the effectiveness of selected bacterial strains in slowing down the progression of AD. It is proven that probiotics modulate the inflammatory process, counteract with oxidative stress, and modify gut microbiota. Thus, this review summarizes the current evidence, diversity of bacterial strains, defects of gut brain axis in AD, harmful bacterial for AD, and the mechanism of action of probiotics in preventing AD. A literature search on selected databases such as PubMed, Semantic Scholar, Nature, and Springer link have identified potentially relevant articles to this topic. However, upon consideration of inclusion criteria and the limitation of publication year, only 22 articles have been selected to be further reviewed. The search query includes few sets of keywords as follows. (1) Probiotics OR gut microbiome OR microbes AND (2) Alzheimer OR cognitive OR aging OR dementia AND (3) clinical trial OR in vivo OR animal study. The results evidenced in this study help to clearly illustrate the relationship between probiotic supplementation and AD. Thus, this systematic review will help identify novel therapeutic strategies in the future as probiotics are free from triggering any adverse effects in human body.
  8. Naomi R, Rusli RNM, Huat TS, Embong H, Bahari H, Kamaruzzaman MA
    Nutrients, 2023 Mar 21;15(6).
    PMID: 36986254 DOI: 10.3390/nu15061523
    Maternal obesity is an intergenerational vicious cycle and one of the primary causes of cognitive deficits and high anxiety levels in offspring, which often manifest independently of sex. It is proven that curbing the intergenerational inheritance of obesity through early intervention during the gestation period has a positive outcome on the body composition, cognitive function, and anxiety level of the offspring. A recent discovery shows that the consumption of Elateriospermum tapos (E. tapos) seed extract modulates body mass and ameliorates stress hormones in obese dams, while a probiotic bacterial strain can cross the placenta and boost a child's memory. Thus, we speculate that probiotics are the best medium to integrate plant extract (E. tapos extract) to access the effect on the child's cognition. Thus, this study aimed to investigate the early intervention of E. tapos yoghurt in obese dams in the cognition and anxiety levels of male offspring. In this study, 40 female rats were fed with a high-fat diet (HFD) to induce obesity before pregnancy, while another 8 rats were fed with standard rat pellets for 16 weeks. Upon successful copulation, treatment was initiated for the obese dams up to the postnatal day (PND) 21. The groups included normal chow and saline (NS), HFD and saline (HS), HFD and yoghurt (HY), HFD and 5 mg/kg E. tapos yoghurt (HYT5), HFD and 50 mg/kg E. tapos yoghurt (HYT50), and HFD and 500 mg/kg E. tapos yoghurt (HYT500). All rats were euthanised on PND 21, and the body mass index (BMI), Lee index, and waist circumference were measured for the male offspring. Hippocampal-dependent memory tests and open field tests were conducted to access for cognition and anxiety status. Fasting blood glucose (FBG), total fat (%), insulin, leptin, lipid profile, and antioxidant parameter on serum and hypothalamus (FRAP and GSH) were accessed on PND 21. The result shows male offspring of 50 mg/kg-supplemented obese dams have comparable total fat (%), lipid profile, insulin level, FBG level, plasma insulin level, recognition index, low anxiety level, and improved hypothalamic FRAP and GSH levels to the normal group. In conclusion, this study highlights that the effect of early intervention of our novel formulation of E. tapos yoghurt in obese dams alleviates cognitive deficits and anxiety in male offspring by modulating metabolic profiles at the dose of 50 mg/kg.
  9. Naomi R, Teoh SH, Rusli RNM, Embong H, Bahari H, Kumar J
    Nutrients, 2023 May 15;15(10).
    PMID: 37242195 DOI: 10.3390/nu15102312
    Maternal obesity can be considered an intergenerational cycle and is also an important indicator of cognitive impairments. It is thought that using natural products is the best and safest way to combat maternal obesity and associated complications. Recent studies have shown that Elateriospermum tapos (E. tapos) contains bioactive compounds with anti-obesity effects, and yoghurt is a convenient medium for supplementing obese maternal rats with E. tapos extract. Thus, the aim of this study is to investigate the impact of E. tapos in yoghurt on maternally obese rats' cognitive function supplemented with a high-fat diet (HFD). In this study, 48 female Sprague-Dawley rats were used. The rats were fed HFD for a period of 16 weeks to induce obesity, after which they were allowed to mate. Upon confirmation of pregnancy, obese rats were given varying doses of E. tapos (5, 50, and 500 mg/kg) in yoghurt until postnatal (PND) day 21. On PND 21, the dams' body mass index (BMI), Lee index, abdominal circumference, oxidative status, and metabolic profile were measured. The behavioral tests (open field, place, and object recognition) were conducted on PND 21 to access memory. The results show that the 50 and 500 mg/kg E. tapos in yoghurt supplemented groups had similar BMI, Lee index, abdominal circumference, lipid profile, FBG, insulin, FRAP, and GSH levels, as well as a similar recognition index, in comparison with the control group supplemented with saline. In conclusion, the results of this study indicate that the newly formulated E. tapos in yogurt can act as an anti-obesity agent in maternal obesity, alleviate anxiety, and enhance hippocampal-dependent memory.
  10. Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Bahari H, et al.
    Antioxidants (Basel), 2023 May 10;12(5).
    PMID: 37237937 DOI: 10.3390/antiox12051071
    Obesity is a chronic low-grade inflammatory condition that induces the generation of oxidative stress and inflammation. This oxidative stress and inflammation stimulate brain atrophy and some morphological changes in the brain that eventually result in cognitive impairments. However, there is no exact study that has summarized the role of oxidative stress and inflammation in obesity and its impact on cognitive impairments. Thus, the objective of this review is to recapitulate the current role of oxidative stress and inflammation in cognitive decline based on in vivo evidence. A comprehensive search was performed in Nature, Medline and Ovid, ScienceDirect, and PubMed, and the search was limited to the past 10 years of publication. From the search, we identified 27 articles to be further reviewed. The outcome of this study indicates that a greater amount of fat stored in individual adipocytes in obesity induces the formation of reactive oxygen species and inflammation. This will lead to the generation of oxidative stress, which may cause morphological changes in the brain, suppress the endogenous antioxidant system, and promote neuroinflammation and, eventually, neuronal apoptosis. This will impair the normal function of the brain and specific regions that are involved in learning, as well as memory. This shows that obesity has a strong positive correlation with cognitive impairments. Hence, this review summarizes the mechanism of oxidative stress and inflammation that induce memory loss based on animal model evidence. In conclusion, this review may serve as an insight into therapeutic development focusing on oxidative stress and inflammatory pathways to manage an obesity-induced cognitive decline in the future.
  11. Naomi R, Bahari H, Yazid MD, Othman F, Zakaria ZA, Hussain MK
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639164 DOI: 10.3390/ijms221910816
    Hyperglycemia is a condition with high glucose levels that may result in dyslipidemia. In severe cases, this alteration may lead to diabetic retinopathy. Numerous drugs have been approved by officials to treat these conditions, but usage of any synthetic drugs in the long term will result in unavoidable side effects such as kidney failure. Therefore, more emphasis is being placed on natural ingredients due to their bioavailability and absence of side effects. In regards to this claim, promising results have been witnessed in the usage of Ipomoea batatas (I. batatas) in treating the hyperglycemic and dyslipidemic condition. Thus, the aim of this paper is to conduct an overview of the reported effects of I. batatas focusing on in vitro and in vivo trials in reducing high glucose levels and regulating the dyslipidemic condition. A comprehensive literature search was performed using Scopus, Web of Science, Springer Nature, and PubMed databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) Beneficial effect OR healing OR intervention AND (2) sweet potato OR Ipomoea batatas OR traditional herb AND (3) blood glucose OR LDL OR lipid OR cholesterol OR dyslipidemia. Only articles published from 2011 onwards were selected for further analysis. This review includes the (1) method of intervention and the outcome (2) signaling mechanism involved (3) underlying mechanism of action, and the possible side effects observed based on the phytoconstiuents isolated. The comprehensive literature search retrieved a total of 2491 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 23 articles were chosen for further review. The results from these articles indicate that I. batatas has proven to be effective in treating the hyperglycemic condition and is able to regulate dyslipidemia. Therefore, this systematic review summarizes the signaling mechanism, mechanism of action, and phytoconstituents responsible for those activities of I. batatas in treating hyperglycemic based on the in vitro and in vivo study.
  12. Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Mamat-Hamidi K, et al.
    Foods, 2023 Sep 26;12(19).
    PMID: 37835227 DOI: 10.3390/foods12193575
    Maternal obesity, characterized by an elevated body mass index (BMI) during pregnancy, is known to have adverse effects on the offspring. However, a recent study suggests that Elateriospermum tapos (E. tapos) yogurt may hold potential in mitigating excessive weight retention post-pregnancy. Thus, this study aims to employ network pharmacology to explore the pharmacological effects of the bioactive compounds present in E. tapos yogurt against maternal obesity. Initially, a screening process is conducted to identify the bioactive compounds in E. tapos yogurt, followed by the prediction of potential gene targets for these compounds using Swiss Target Prediction and the SuperPred databases. Maternal obesity-associated genes are sourced from the OMIM, DisGeNet, and GeneCards databases. The interaction between the identified compounds and maternal obesity genes is established via protein-protein interaction analysis, gene ontology examination, and KEGG pathway analysis. To validate the results, molecular docking studies are conducted using AutoDock Tools software. The findings reveal that out of the 64 compounds analyzed, three meet the screening criteria, resulting in a total of 380 potential gene targets. Among these targets, 240 are shared with maternal obesity-related genes. Further analysis demonstrates the favorable affinity of these active compounds with key targets, linking them to biological processes involving protein phosphorylation, inflammation, as well as the pathways related to lipid metabolism, atherosclerosis, and the other signaling pathways. In conclusion, this study provides valuable insights into the potential pharmacological effects of the bioactive compounds found in E. tapos yogurt against maternal obesity. These findings open avenues for further exploration and potential therapeutic interventions targeting maternal obesity.
  13. Byrne EM, Psychiatric Genetics Consortium Major Depressive Disorder Working Group, Raheja UK, Stephens SH, Heath AC, Madden PA, et al.
    J Clin Psychiatry, 2015 Feb;76(2):128-34.
    PMID: 25562672 DOI: 10.4088/JCP.14m08981
    OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality.

    METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality.

    RESULTS: The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality.

    CONCLUSIONS: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

  14. Maier R, Moser G, Chen GB, Ripke S, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Coryell W, et al.
    Am J Hum Genet, 2015 Feb 05;96(2):283-94.
    PMID: 25640677 DOI: 10.1016/j.ajhg.2014.12.006
    Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk.
  15. Hanim A, Mohamed IN, Mohamed RMP, Mokhtar MH, Makpol S, Naomi R, et al.
    Nutrients, 2023 Jul 05;15(13).
    PMID: 37447362 DOI: 10.3390/nu15133036
    Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.
  16. Rusli RNM, Naomi R, Yazid MD, Embong H, Perumal K, Othman F, et al.
    Toxins (Basel), 2023 Feb 03;15(2).
    PMID: 36828439 DOI: 10.3390/toxins15020125
    The Bouea macrophylla fruit is native to Malaysia and is known for its many beneficial effects on one's health. Probiotics are well-known for their roles as anti-inflammatory, antioxidant, and anti-tumour properties due to their widespread use. As a result, the purpose of this study was to incorporate the ethanolic extract of Bouea macrophylla into yoghurt and then assess the rodents for any toxicological effects. According to the findings of the nutritional analysis, each 100 mL serving of the newly formulated yoghurt contains 3.29 g of fat, 5.79 g of carbohydrates, 2.92 g of total protein, and 2.72 g of sugar. The ability of the newly developed yoghurt to stimulate the growth of Lactobacilli was demonstrated by the fact that the peak intensity of Lactobacillus species was measured at 1.2 × 106 CFU/g while the titratable acidity of the lactic acid was measured at 0.599 CFU/g. In order to carry out the toxicological evaluation, forty-eight male Sprague Dawley (SD) rats were utilized. Oral administration of single doses of 2000 mg/kg over the course of 14 days was used for the study of acute toxicity. Subacute toxicity was studied by giving animals Bouea macrophylla yoghurt (BMY) at repeated doses of 50, 250, 500, and 1000 mg/kg/day over a period of 28 days, while the control group was given normal saline. The results of the acute toxicity test revealed that rats treated with increasing doses up to a maximum of 2000 mg/kg exhibited no signs of toxicity. After an additional 14 days without treatment, acute toxicity of a single dose (2000 mg/kg) of BMY did not show any treatment-related toxicity in any of the rats that were observed. According to the data from the subacute toxicity study, there were no differences between the treated groups and the control groups in terms of food and water intake, body weight, plasma biochemistry (AST, ALT, ALP, and creatinine), haematological products, or organ weights. The architecture of the liver, heart, and kidney were all found to be normal upon histological examination. This indicates that oral consumption of BMY did not result in any negative effects being manifested in the rodents.
  17. Hisamuddin ASB, Naomi R, Bin Manan KA, Bahari H, Yazid MD, Othman F, et al.
    Front Pharmacol, 2023;14:1132087.
    PMID: 37077809 DOI: 10.3389/fphar.2023.1132087
    This study assessed the toxicity of lutein-rich purple sweet potato leaf (PSPL) extract in male Sprague-Dawley rats. Methods and study design: A total of 54 adult male Sprague-Dawley rats were used. For the acute toxicity study, three rats in the acute control group were fed 2,000 mg/kg of PSPL for 14 days. The subacute toxicity study included six rats each in four groups administered 50, 250, 500, or 1,000 mg/kg for 28 days and observed for further 14 days without treatment in the subacute control and subacute satellite groups. Changes in body weight; blood biochemistry; hematological parameters; relative organ weight; and histological sections of the heart, kidney, liver, pancreas, aorta, and retina were observed for signs of toxicity. Results: The gradual increase in weekly body weight, normal level full blood count, normal liver and kidney profile, relative organ weight, and histological sections of all stained organ tissue in the treated group compared with the acute, subacute, and satellite control groups demonstrated the absence of signs of toxicity. Conclusion: Lutein-rich PSPL extract shows no signs of toxicity up to 2,000 mg/kg/day.
  18. Hisamuddin ASB, Naomi R, Manan KAB, Bahari H, Othman F, Embong H, et al.
    Front Pharmacol, 2023;14:1175907.
    PMID: 37274105 DOI: 10.3389/fphar.2023.1175907
    The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague-Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.
  19. Naomi R, Rusli RNM, Othman F, Balan SS, Abidin AZ, Embong H, et al.
    Front Endocrinol (Lausanne), 2023;14:1131830.
    PMID: 37415666 DOI: 10.3389/fendo.2023.1131830
    Maternal obesity is the key predictor for childhood obesity and neurodevelopmental delay in the offspring. Medicinal plants are considered to be the safe and best option, and at the same time, probiotic consumption during pregnancy provides beneficial effects for both the mother and the child. Current research has shown that Elateriospermum tapos (E. tapos) yoghurt is safe to consume and consists of many bioactive compounds that can exert an anti-obesity effect. Thus, this study has been designed to study the role of E. tapos yoghurt in mitigating maternal obesity. In this study, a total of 48 female Sprague Dawley (SD) rats were assigned to six groups, with eight rats per group, and obesity was induced over 16 weeks with a high-fat diet (HFD) pellet. On the 17th week, the rats were allowed to mate and pregnancy was confirmed through vaginal smear. The obese induced group was further divided into negative and positive control groups, followed by E. tapos yoghurt treatment groups with three different concentrations (5, 50, and 500 mg/kg). The changes in body weight, calorie intake, lipid profile, liver profile, renal profile, and histopathological analysis were measured on postnatal day (PND) 21. The results show that the group with the highest concentration of E. tapos yoghurt (HYT500) supplementation shows gradual reduction in body weight and calorie intake on PND 21 and modulates the lipid level, liver, and renal enzymes to a normal level similar to the normal group. In histological analysis, HYT500 reverses the damage caused by HFD in liver and colon, and reverses the adipocytes' hypertrophy in retroperitoneal white adipose tissue and visceral fat. In conclusion, supplementation of E. tapos yoghurt during the gestational period up to weaning is effective in the gradual weight loss of maternal obese dams from the 500-mg/kg-supplemented group in this study.
  20. Milaneschi Y, Lamers F, Peyrot WJ, Baune BT, Breen G, Dehghan A, et al.
    JAMA Psychiatry, 2017 12 01;74(12):1214-1225.
    PMID: 29049554 DOI: 10.1001/jamapsychiatry.2017.3016
    Importance: The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode.

    Objective: To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin).

    Design, Setting, and Patients: This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017.

    Main Outcomes and Measures: Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased.

    Results: Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3).

    Conclusions and Relevance: The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.

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