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  1. Development, characterization and commercial application of palm based dihydroxystearic acid and its derivatives: an overview
    Koay GF, Chuah TG, Zainal-Abidin S, Ahmad S, Choong TS
    J Oleo Sci, 2011;60(5):237-65.
    PMID: 21502724
    Hydroxyl fatty acids and their derivatives are of high value due to their wide range of industrial application, including cosmetic, food, personal care and pharmaceutical products. Realizing the importance of hydroxyl fatty acids, and yet due to the absence of the conventional starting raw materials, Malaysia has developed 9,10-dihydroxystearic acid (9,10-DHSA) and its derivatives from locally abundant palm based oils. The aim of this article is to provide a general description of the works that have thus far being done on palm based 9,10-DHSA: starting from its conception and production from commercial grade palm based crude oleic acid via epoxidation and hydrolysis, purification through solvent crystallization and characterization through wet and analytical chemistry, moving on to developmental works done on producing its derivatives through blending, esterification, amidation and polymerization, and completing with applications of 9,10-DHSA and its derivatives, e.g. DHSA-stearates and DHSA-estolides, in commercial products such as soaps, deodorant sticks and shampoos. This article incorporates some of the patent filed technological knowhow on 9,10-DHSA and its derivatives, and will also point out some of the shortcomings in previously published documents and provide some recommendations for future research works in mitigating these shortcomings.
  2. miR-3099 promotes neurogenesis and inhibits astrogliogenesis during murine neural development
    Zainal Abidin S, Fam SZ, Chong CE, Abdullah S, Cheah PS, Nordin N, et al.
    Gene, 2019 May 20;697:201-212.
    PMID: 30769142 DOI: 10.1016/j.gene.2019.02.014
    MicroRNA-3099 is highly expressed during neuronal differentiation and development of the central nervous system. Here we characterised the role of miR-3099 during neural differentiation and embryonic brain development using a stable and regulatable mouse embryonic stem cell culture system for miR-3099 expression and in utero electroporation of miR-3099 expression construct into E15.5 embryonic mouse brains. In the in vitro system, miR-3099 overexpression upregulated gene related to neuronal markers such as Tuj1, NeuN, Gat1, vGluT1 and vGluT2. In contrast, gene related to astrocyte markers (Gfap, S100β and Slc1a3) were suppressed upon overexpression of miR-3099. Furthermore, miR-3099 overexpression between E15.5 and E18.5 mouse embryonic brains led to disorganised neuronal migration potentially due to significantly decreased Gfap+ cells. Collectively, our results indicated that miR-3099 plays a role in modulating and regulating expression of key markers involved in neuronal differentiation. In silico analysis was also performed to identify miR-3099 homologues in the human genome, and candidates were validated by stem-loop RT-qPCR. Analysis of the miR-3099 seed sequence AGGCUA against human transcriptomes revealed that a potential miRNA, mds21 (Chr21:39186698-39186677) (GenBank accession ID: MK521584), was 100% identical to the miR-3099 seed sequence. Mds21 expression was observed and validated in various human cell lines (293FT, human Wharton's jelly and dental pulp mesenchymal stem cells, and MCF-7, MDA-MB-231, C-Sert, SW780, RT112, 5637, EJ28 and SH-SY5Y cells), with the highest levels detected in human mesenchymal stem cell lines. The analysis validated mds21 as a novel miRNA and a novel homologue of miR-3099 in the human genome.
  3. Fulltext Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells
    Reza Etemadi M, Ling KH, Zainal Abidin S, Chee HY, Sekawi Z
    PLoS One, 2017;12(5):e0176947.
    PMID: 28558071 DOI: 10.1371/journal.pone.0176947
    Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
  4. Fulltext ABC approach for the management of adults with hyperthyroidism: A practical strategy in primary care
    Jamaluddin J, Zainal Abidin S, Kathitasapathy G, Mohamad Isa MZ, Mohamed Kamel MA, Kaur P, et al.
    Malays Fam Physician, 2023;18:57.
    PMID: 37814670 DOI: 10.51866/rv.303
    Hyperthyroidism is commonly seen in primary care settings. However, the management of hyperthyroidism might be unclear to primary care doctors. Various guidelines have been published to assist clinicians in the management of thyroid disorders at various levels of care. The extensive coverage of these guidelines may not appeal to busy clinicians, and the guidelines do not focus on often resource-limited primary care settings. In this article, we aim to describe a practical guide for managing hyperthyroidism in primary care settings using an ABC approach.
  5. Fulltext Cardiovascular disease risk factors among older people: Data from the National Health and Morbidity Survey 2015
    Sazlina SG, Sooryanarayana R, Ho BK, Omar MA, Krishnapillai AD, Mohd Tohit N, et al.
    PLoS One, 2020;15(10):e0240826.
    PMID: 33085718 DOI: 10.1371/journal.pone.0240826
    Study on cardiovascular disease (CVD) risk factors and their prevalence among the older people in Malaysia is limited. We aimed to determine the prevalence and factors associated with CVD risk factors using the non-laboratory Framingham Generalized 10-Year CVD risk score among older people in Malaysia. This was a population-based cross-sectional study using data of 3,375 participants aged ≥60 years from the National Health and Morbidity Survey 2015. Sociodemographic, health factors and clinical assessments (anthropometry and blood pressure) were included. Complex survey analysis was used to obtain prevalence with 95% confidence intervals (CI). We applied ordinal regression to determine the factors associated with CVD risk. The prevalence for the high 10-year CVD risk was 72.1%. Body mass index was higher among those aged 60-69 years in men (25.4kg/m2, 95%CI 25.1-25.8) and women (26.7kg/m2, 95%CI 26.3-27.1) than the other age groups. The factors associated with moderate and high 10-year CVD risk were Malay ethnicity (Odds Ratio(OR) 0.76, 95%CI 0.63-0.92, p = 0.004), unmarried status (OR 1.55, 95%CI 1.22-1.97, p<0.001) and physically inactive (OR 0.72, 95%CI 0.55-0.95, p = 0.020). There is a need for future study to evaluate preventive strategies to improve the health of older people in order to promote healthy ageing.
  6. Fulltext Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams
    Talik Sisin NN, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2020;15:7805-7823.
    PMID: 33116502 DOI: 10.2147/IJN.S269214
    Purpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.

    Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.

    Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.

    Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.

  7. Fulltext Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing
    Othman NS, Aminuddin A, Zainal Abidin S, Syafruddin SE, Ahmad MF, Mohd Mokhtar N, et al.
    Life (Basel), 2023 May 31;13(6).
    PMID: 37374078 DOI: 10.3390/life13061296
    Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.
  8. Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring
    Mohd Isa NI, Syafruddin SE, Mokhtar MH, Zainal Abidin S, Jaffar FHF, Ugusman A, et al.
    Int J Mol Sci, 2023 Nov 28;24(23).
    PMID: 38069164 DOI: 10.3390/ijms242316842
    Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.
  9. Fulltext Impact of offspring endothelial function from de novo hypertensive disorders during pregnancy: An evidence-based review
    Abdull Sukor AN, Ankasha SJ, Ugusman A, Aminuddin A, Mokhtar NM, Zainal Abidin S, et al.
    Front Surg, 2022;9:967785.
    PMID: 36420416 DOI: 10.3389/fsurg.2022.967785
    De novo hypertensive disorders of pregnancy (HDP) which consist of gestational hypertension and preeclampsia affect maternal and offspring morbidity and mortality, and potentially increase the risk of cardiovascular disease in the offspring. It is well known that de novo HDP causes various maternal complications, including cardiovascular diseases, placental abruption and liver and kidney failure. However, there are studies suggesting that offspring of pregnancies complicated by de novo HDP have an increased risk of long-term cardiovascular disease. The endothelium is an important regulator of vascular function, and its dysfunction is highly associated with the development of cardiovascular diseases. Hence, this review aimed to systematically identify articles related to the effect of de novo HDP on the endothelial function of the offspring. A computerized database search was conducted on PubMed, Scopus, and Medline from 1976 until 2022. A total of 685 articles were obtained. We identified another three additional articles through review articles and Google Scholar. Altogether, we used 13 articles for data extraction. All studies reported that endothelial function was impaired in the offspring of de novo HDP. This is most likely attributed to impaired vasodilation, subclinical atherosclerosis formation, inflammation, and dysregulated epigenetic regulation of endothelial functions.
  10. Fulltext MiR-3099 is Overexpressed in Differentiating 46c Mouse Embryonic Stem Cells upon Neural Induction
    Zainal Abidin S, Abbaspourbabaei M, Ntimi CM, Siew WH, Pike-See C, Rosli R, et al.
    Malays J Med Sci, 2014 Dec;21(Spec Issue):27-33.
    PMID: 25941460 MyJurnal
    MicroRNAs (miRNAs) have a crucial role in gene expression regulation and protein synthesis, especially in the central nervous system. In developing mouse embryos a novel miRNA, miR-3099, is highly expressed, particularly in the central nervous system. This study aims to determine the expression of miR-3099 during cellular differentiation of 46C mouse embryonic stem cells after neural induction with N2/B27 medium.
  11. Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje down syndrome mouse model
    Lee HC, Md Yusof HH, Leong MP, Zainal Abidin S, Seth EA, Hewitt CA, et al.
    Int J Neurosci, 2019 Sep;129(9):871-881.
    PMID: 30775947 DOI: 10.1080/00207454.2019.1580280
    Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.
  12. Multidirectional insights into the phytochemical, biological, and multivariate analysis of the famine food plant (Calligonum polygonoides L).: A novel source of bioactive phytocompounds
    Pervaiz I, Saleem H, Sarfraz M, Imran Tousif M, Khurshid U, Ahmad S, et al.
    Food Res Int, 2020 11;137:109606.
    PMID: 33233202 DOI: 10.1016/j.foodres.2020.109606
    Calligonum polygonoides L. also known as famine food plant, is normally consumed in times of food scarcity in India and Pakistan and also used traditionally in the management of common diseases. The present design aims to provide an insight into the medicinal potential of four solvent extracts of C. polygonoides via an assessment of its phytochemical profile, antioxidant and enzyme inhibitory potential. Phytochemical composition was estimated by deducing total bioactive constituents, UHPLC-MS secondary metabolites profile, and HPLC phenolic quantification. Antioxidant potential was determined via six methods (radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum total antioxidant capacity and metal chelation activity). Enzyme inhibitory potential was assessed against clinical enzymes (acetylcholinesterase -AChE, butyrylcholinesterase -BChE, tyrosinase, and α-amylase). The highest amounts of phenolic contents were found in chloroform extract (76.59 mg GAE/g extract) which may be attributed to its higher radical scavenging, reducing power and tyrosinase inhibition potential. The n-butanol extract containing the maximum amount of flavonoids (55.84 mg RE/g extract) exhibited highest metal chelating capacity. Similarly, the n-hexane extract was found to be most active against AChE (4.65 mg GALAE/g extract), BChE (6.59 mg GALAE/g extract), and α-amylase (0.70 mmol ACAE/g extract) enzymes. Secondary metabolite assessment of the crude methanol extract as determined by UHPLC-MS analysis revealed the presence of 24 (negative ionization mode) and 15 (positive ionization mode) secondary metabolites, with most of them belonging to phenolic, flavonoids, terpene, and alkaloid groups. Moreover, gallic acid and naringenin were the main phenolics quantified by HPLC-PDA analysis in all the tested extracts (except n-butanol extract). PCA statistical analysis was also conducted to establish any possible relationship amongst bioactive contents and biological activities. Overall, the C. polygonoides extracts could be further considered to isolate bioactive enzyme inhibitory and antioxidant natural phytocompounds.
  13. Fulltext Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy
    Sisin NNT, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2019;14:9941-9954.
    PMID: 31908451 DOI: 10.2147/IJN.S228919
    Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.

    Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.

    Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.

    Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.

  14. Fulltext In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts
    Ling KH, Brautigan PJ, Moore S, Fraser R, Leong MP, Leong JW, et al.
    Data Brief, 2016 Jun;7:282-90.
    PMID: 26958646 DOI: 10.1016/j.dib.2016.01.045
    SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.
  15. Fulltext DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients
    Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.
    BMC Neurol, 2015;15:59.
    PMID: 25896831 DOI: 10.1186/s12883-015-0316-2
    Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.
  16. Fulltext Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
    Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.
    Sci Rep, 2021 Feb 15;11(1):3847.
    PMID: 33589712 DOI: 10.1038/s41598-021-83222-z
    Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
  17. Fulltext Bioactivity and Pharmacological Potential of Date Palm (Phoenix dactylifera L.) Against Pandemic COVID-19: a Comprehensive Review
    Ahmad Mohd Zain MR, Abdul Kari Z, Dawood MAO, Nik Ahmad Ariff NS, Salmuna ZN, Ismail N, et al.
    Appl Biochem Biotechnol, 2022 Oct;194(10):4587-4624.
    PMID: 35579740 DOI: 10.1007/s12010-022-03952-2
    A novel coronavirus disease (COVID-19) or severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), transmitted from person to person, has quickly emerged as the pandemic responsible for the current global health crisis. This infection has been declared a global pandemic, resulting in a concerning number of deaths as well as complications post-infection, primarily among vulnerable groups particularly older people and those with multiple comorbidities. In this article, we review the most recent research on the role of date palm (Phoenix dactylifera L.) fruits (DPFs) to prevent or treat COVID-19 infection. The mechanisms underlying this preventive or therapeutic effect are also discussed in terms of bioactivity potentials in date palm, e.g., antimicrobial, antioxidant, anticancer, anti-diabetic, anti-inflammatory, neuroprotective, and hemolytic potential, as well as prospect against COVID-19 disease and the potential product development. Therefore, it can be concluded that regular consumption of DPFs may be associated with a lower risk of some chronic diseases. Indeed, DPFs have been widely used in folk medicine since ancient times to treat a variety of health conditions, demonstrating the importance of DPFs as a nutraceutical and source of functional nourishment. This comprehensive review aims to summarize the majority of the research on DPFs in terms of nutrient content and biologically active components such as phenolic compounds, with an emphasis on their roles in improving overall health as well as the potential product development to ensure consumers' satisfaction in a current pandemic situation. In conclusion, DPFs can be given to COVID-19 patients as a safe and effective add-on medication or supplement in addition to routine treatments.
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