Displaying publications 1 - 20 of 71 in total

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  1. Zailan AAD, Karunakaran T, Santhanam R, Suriaty Yaakop A, Mohan S, Abu Bakar MH, et al.
    Chem Biodivers, 2024 Mar;21(3):e202301936.
    PMID: 38268343 DOI: 10.1002/cbdv.202301936
    The genus Calophyllum from the family Calophyllaceae has been extensively investigated in the past due to its rich source of bioactive phenolics such as coumarins, chromanones, and xanthones. In this study, phytochemical investigation on the stem bark of Calophyllum havilandii has afforded a new 4-propyldihydrocoumarin derivative, havilarin (1) together with calolongic acid (2), caloteysmannic acid (3), isocalolongic acid (4), euxanthone (5), and β-sitosterol (6). The chemical structure of compound 1 was elucidated and established based on detailed spectroscopic techniques, including MS, IR, UV, 1D and 2D NMR. The results of anti-bacillus study indicated that the chloroform extract showed promising activities with MIC value ranging between 0.5 to 1 μg/mL on selected bacillus strains. Besides, the plant extracts and compounds 1-4 were assessed for their cytotoxicity potential on HL-7702 cell line. All the tested plant extracts and respective chemical constituents displayed non-cytotoxic activity on HL-7702 cell line.
  2. Aboulaghras S, Khalid A, Makeen HA, Alhazmi HA, Albratty M, Mohan S, et al.
    Front Biosci (Landmark Ed), 2024 Feb 05;29(2):55.
    PMID: 38420797 DOI: 10.31083/j.fbl2902055
    Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.
  3. Seriramulu VP, Suppiah S, Lee HH, Jang JH, Omar NF, Mohan SN, et al.
    Med J Malaysia, 2024 Jan;79(1):102-110.
    PMID: 38287765
    INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders.

    MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD.

    RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing.

    CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.

  4. Sandrasaigaran P, Mohan S, Segaran NS, Lee TY, Radu S, Hasan H
    Int J Food Microbiol, 2023 Dec 16;407:110390.
    PMID: 37722349 DOI: 10.1016/j.ijfoodmicro.2023.110390
    Filth flies at wet markets can be a vector harbouring multiple antimicrobial-resistant (MAR) nontyphoidal Salmonella (NTS), and such strains are a significant threat to public health as they may cause severe infections in humans. This study aims to investigate the prevalence of antimicrobial-resistant NTS, especially Salmonella Enteritidis and S. Typhimurium harboured by filth flies at wet markets, and investigate their survival in the simulated gastric fluid (SGF). Filth flies (n = 90) were captured from wet markets in Klang, Malaysia, and processed to isolate Salmonella spp. The isolates (n = 16) were identified using the multiplex-touchdown PCR and assessed their antimicrobial susceptibility against 11 antimicrobial agents. Finally, three isolates with the highest MAR index were subjected to SGF survival tests. It was observed that 17.8 % of flies (n = 16/90) harbouring Salmonella, out of which 10 % (n = 9/90) was S. Enteritidis, 2.2 % (n = 2/90) was S. Typhimurium, and 5.6 % was unidentified serotypes of Salmonella enterica subsp. I. 43.8 % (n = 7/16) were confirmed as MAR, and they were observed to be resistant against ampicillin, chloramphenicol, kanamycin, streptomycin, and nalidixic acid. Three strains, F35, F75, and F85 demonstrated the highest MAR index and were able to survive (>6-log10) in the SGF (180 min), indicating their potential virulence and invasiveness. This study provides significant insights into the prevalence and severity of MAR nontyphoidal Salmonella harboured by filth flies in wet markets, which may help inform strategies for controlling the spread and outbreak of foodborne disease.
  5. Freedberg DE, Segall L, Liu B, Jacobson JS, Mohan S, George V, et al.
    Kidney360, 2023 Dec 06.
    PMID: 38055708 DOI: 10.34067/KID.0000000000000335
    BACKGROUND: Approaches to treating end-stage kidney disease (ESKD) may vary internationally based on the availability of care and other factors. We performed a systematic review to understand the international variability in ESKD epidemiology, management, and outcomes.

    METHODS: We systematically searched Pubmed for population-based studies of chronic kidney disease (CKD) and ESKD epidemiology and management. Population-level data from 23 pre-designated nations were eligible for inclusion if they pertained to people receiving dialysis or kidney transplant for ESKD. When available, government websites were utilized to identify and extract data from relevant kidney registries . Measures gathered included those related to the prevalence and mortality of ESKD; the availability of nephrologists; per capita healthcare expenditures; and use of erythropoietin stimulating agents (ESAs).

    RESULTS: We obtained data from the United States (US), 7 nations in Eastern Europe, 4 each in Western Europe, Latin America, and Africa, and 3 in Asia. Documented prevalence of ESKD per million population varied from a high of 3,600 (Malaysia) to a low of 67 (Senegal). Annual mortality associated with ESKD varied from 31% (Ethiopia and Senegal) to 10% (UK). Nephrologist availability per million population varied from 40 (Japan) to <1 (South Africa) and was associated with per capita healthcare expenditures.

    CONCLUSIONS: The delivery of kidney care related to ESKD varies widely among countries. Higher per capita healthcare spending is associated with increased delivery of kidney care. However, in part because documentation of kidney disease varies widely, it is difficult to determine how outcomes related to ESKD may vary across nations.

  6. El Omari N, Lee LH, Bakrim S, Makeen HA, Alhazmi HA, Mohan S, et al.
    Biomed Pharmacother, 2023 Aug;164:114774.
    PMID: 37224749 DOI: 10.1016/j.biopha.2023.114774
    Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
  7. Abdulabbas Hasan M, Mohan S, Rahman HS, Othman HH, Hamasalih Omer S, Farasani A
    Drug Chem Toxicol, 2023 May;46(3):588-596.
    PMID: 35506235 DOI: 10.1080/01480545.2022.2069803
    Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.
  8. Sonia JJ, Jayachandran P, Md AQ, Mohan S, Sivaraman AK, Tee KF
    Diagnostics (Basel), 2023 Feb 14;13(4).
    PMID: 36832207 DOI: 10.3390/diagnostics13040723
    Over the past few decades, the prevalence of chronic illnesses in humans associated with high blood sugar has dramatically increased. Such a disease is referred to medically as diabetes mellitus. Diabetes mellitus can be categorized into three types, namely types 1, 2, and 3. When beta cells do not secrete enough insulin, type 1 diabetes develops. When beta cells create insulin, but the body is unable to use it, type 2 diabetes results. The last category is called gestational diabetes or type 3. This happens during the trimesters of pregnancy in women. Gestational diabetes, however, disappears automatically after childbirth or may continue to develop into type 2 diabetes. To improve their treatment strategies and facilitate healthcare, an automated information system to diagnose diabetes mellitus is required. In this context, this paper presents a novel system of classification of the three types of diabetes mellitus using a multi-layer neural network no-prop algorithm. The algorithm uses two major phases in the information system: the training phase and the testing phase. In each phase, the relevant attributes are identified using the attribute-selection process, and the neural network is trained individually in a multi-layer manner, starting with normal and type 1 diabetes, then normal and type 2 diabetes, and finally healthy and gestational diabetes. Classification is made more effective by the architecture of the multi-layer neural network. To provide experimental analysis and performances of diabetes diagnoses in terms of sensitivity, specificity, and accuracy, a confusion matrix is developed. The maximum specificity and sensitivity values of 0.95 and 0.97 are attained by this suggested multi-layer neural network. With an accuracy score of 97% for the categorization of diabetes mellitus, this proposed model outperforms other models, demonstrating that it is a workable and efficient approach.
  9. Gupta V, Santosh KC, Arora R, Ciano T, Kalid KS, Mohan S
    Inf Process Manag, 2022 Mar;59(2):102810.
    PMID: 35165495 DOI: 10.1016/j.ipm.2021.102810
    Starting from December 2019, the novel COVID-19 threatens human lives and economies across the world. It was a matter of grave concern for the governments of all the countries as the deadly virus started expanding its paws over neighboring regions of infected areas. The spread got uncontrollable, thereby leaving no choice for the nations but to impose and observe nationwide lockdown. The lockdown further sorely hit many sectors, which in turn impacted the economy. Manufacturing, agriculture, and the service sector - the three pillars of the economy - have been adversely affected giving a major slow down to the economy belonging to every nation. Several schemes and policies were introduced by different state and central governments to absorb the impact of subsequent lockdowns on individuals. In this paper, we present a then and now analysis of the economy using a socioeconomic framework focusing on factors- unemployment, industrial production, import-export trade, equity markets, currency exchange rate, and gold and silver prices. For all these, we consider India as a case study because the Indian sub-continent has a wide landscape and rich cultural heritage presenting itself as a potential hub for economic activities. A thorough assessment has been made for the period January 2020- June 2020. The assessment will be beneficial to observe the long-term impact of any infectious disease outbreak such as COVID-19 locally and globally.
  10. Gupta V, Jain N, Katariya P, Kumar A, Mohan S, Ahmadian A, et al.
    Chaos Solitons Fractals, 2021 Mar;144:110708.
    PMID: 33519125 DOI: 10.1016/j.chaos.2021.110708
    At the dawn of the year 2020, the world was hit by a significant pandemic COVID-19, that traumatized the entire planet. The infectious spread grew in leaps and bounds and forced the policymakers and governments to move towards lockdown. The lockdown further compelled people to stay under house arrest, which further resulted in an outbreak of emotions on social media platforms. Perceiving people's emotional state during these times becomes critically and strategically important for the government and the policymakers. In this regard, a novel emotion care scheme has been proposed in this paper to analyze multimodal textual data contained in real-time tweets related to COVID-19. Moreover, this paper studies 8-scale emotions (Anger, Anticipation, Disgust, Fear, Joy, Sadness, Surprise, and Trust) over multiple categories such as nature, lockdown, health, education, market, and politics. This is the first of its kind linguistic analysis on multiple modes pertaining to the pandemic to the best of our understanding. Taking India as a case study, we inferred from this textual analysis that 'joy' has been lesser towards everything (~9-15%) but nature (~17%) due to the apparent fact of lessened pollution. The education system entailed more trust (~29%) due to teachers' fraternity's consistent efforts. The health sector witnessed sadness (~16%) and fear (~18%) as the dominant emotions among the masses as human lives were at stake. Additionally, the state-wise and emotion-wise depiction is also provided. An interactive internet application has also been developed for the same.
  11. Jain N, Jhunthra S, Garg H, Gupta V, Mohan S, Ahmadian A, et al.
    Results Phys, 2021 Feb;21:103813.
    PMID: 33495725 DOI: 10.1016/j.rinp.2021.103813
    Coronavirus is a pandemic that has become a concern for the whole world. This disease has stepped out to its greatest extent and is expanding day by day. Coronavirus, termed as a worldwide disease, has caused more than 8 lakh deaths worldwide. The foremost cause of the spread of coronavirus is SARS-CoV and SARS-CoV-2, which are part of the coronavirus family. Thus, predicting the patients suffering from such pandemic diseases would help to formulate the difference in inaccurate and infeasible time duration. This paper mainly focuses on the prediction of SARS-CoV and SARS-CoV-2 using the B-cells dataset. The paper also proposes different ensemble learning strategies that came out to be beneficial while making predictions. The predictions are made using various machine learning models. The numerous machine learning models, such as SVM, Naïve Bayes, K-nearest neighbors, AdaBoost, Gradient boosting, XGBoost, Random forest, ensembles, and neural networks are used in predicting and analyzing the dataset. The most accurate result was obtained using the proposed algorithm with 0.919 AUC score and 87.248% validation accuracy for predicting SARS-CoV and 0.923 AUC and 87.7934% validation accuracy for predicting SARS-CoV-2 virus.
  12. Rahman HS, Tan BL, Othman HH, Chartrand MS, Pathak Y, Mohan S, et al.
    Biomed Res Int, 2020;2020:8857428.
    PMID: 33381591 DOI: 10.1155/2020/8857428
    Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro, in vivo, and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field.
  13. Othman H, Rahman H, Mohan S, Aziz S, Marif H, Ford D, et al.
    PMID: 32922508 DOI: 10.1155/2020/8764096
    This study investigated the in vivo antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC50 7.55 μg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.
  14. Krishnamurithy G, Mohan S, Yahya NA, Mansor A, Murali MR, Raghavendran HRB, et al.
    PLoS One, 2019;14(3):e0214212.
    PMID: 30917166 DOI: 10.1371/journal.pone.0214212
    It has been demonstrated that nanocrystalline forsterite powder synthesised using urea as a fuel in sol-gel combustion method had produced a pure forsterite (FU) and possessed superior bioactive characteristics such as bone apatite formation and antibacterial properties. In the present study, 3D-scaffold was fabricated using nanocrystalline forsterite powder in polymer sponge method. The FU scaffold was used in investigating the physicochemical, biomechanics, cell attachment, in vitro biocompatibility and osteogenic differentiation properties. For physicochemical characterisation, Fourier-transform infrared spectroscopy (FTIR), Energy dispersive X-ray (EDX), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoemission spectrometer (XPS) and Brunauer-Emmett-Teller (BET) were used. FTIR, EDX, XRD peaks and Raman spectroscopy demonstrated correlating to FU. The XPS confirmed the surface chemistry associating to FU. The BET revealed FU scaffold surface area of 12.67 m2/g and total pore size of 0.03 cm3/g. Compressive strength of the FU scaffold was found to be 27.18 ± 13.4 MPa. The human bone marrow derived mesenchymal stromal cells (hBMSCs) characterisation prior to perform seeding on FU scaffold verified the stromal cell phenotypic and lineage commitments. SEM, confocal images and presto blue viability assay suggested good cell attachment and proliferation of hBMSCs on FU scaffold and comparable to a commercial bone substitutes (cBS). Osteogenic proteins and gene expression from day 7 onward indicated FU scaffold had a significant osteogenic potential (p<0.05), when compared with day 1 as well as between FU and cBS. These findings suggest that FU scaffold has a greater potential for use in orthopaedic and/or orthodontic applications.
  15. Omer FAA, Hashim NBM, Ibrahim MY, Dehghan F, Yahayu M, Karimian H, et al.
    Tumour Biol., 2017 Nov;39(11):1010428317731451.
    PMID: 29110583 DOI: 10.1177/1010428317731451
    Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.
  16. Pandy V, Narasingam M, Vijeepallam K, Mohan S, Mani V, Mohamed Z
    Exp Anim, 2017 Aug 05;66(3):283-291.
    PMID: 28450692 DOI: 10.1538/expanim.16-0105
    In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system.
  17. Omer FAA, Hashim NM, Ibrahim MY, Aldoubi AF, Hassandarvish P, Dehghan F, et al.
    BMC Complement Altern Med, 2017 Jul 17;17(1):366.
    PMID: 28716025 DOI: 10.1186/s12906-017-1867-0
    BACKGROUND: Beta-mangostin (BM) is a xanthone-type of natural compound isolated from Cratoxylum arborescens. This study aimed to examine the apoptosis mechanisms induced by BM in a murine monomyelocytic cell line (WEHI-3) in vitro and in vivo.

    METHODS: A WEHI-3 cell line was used to evaluate the cytotoxicity of BM by MTT. AO/PI and Hoechst 33342 dyes, Annexin V, multiparametric cytotoxicity 3 by high content screening (HCS); cell cycle tests were used to estimate the features of apoptosis and BM effects. Caspase 3 and 9 activities, ROS, western blot for Bcl2, and Bax were detected to study the mechanism of apoptosis. BALB/c mice injected with WEHI-3 cells were used to assess the apoptotic effect of BM in vivo.

    RESULTS: BM suppressed the growth of WEHI-3 cells at an IC50value of 14 ± 3 μg/mL in 24 h. The ROS production was increased inside the cells in the treated doses. Both caspases (9 and 3) were activated in treating WEHI-3 cells at 24, 48 and 72 h. Different signs of apoptosis were detected, such as cell membrane blebbing, DNA segmentation and changes in the asymmetry of the cell membrane. Another action by which BM could inhibit WEHI-3 cells is to restrain the cell cycle at the G1/G0 phase. In the in vivo study, BM reduced the destructive effects of leukaemia on the spleen and liver by inducing apoptosis in leukaemic cells.

    CONCLUSION: BM exerts anti-leukaemic properties in vitro and in vivo.

  18. Mohan S, Raghavendran HB, Karunanithi P, Murali MR, Naveen SV, Talebian S, et al.
    ACS Appl Mater Interfaces, 2017 Mar 22;9(11):9291-9303.
    PMID: 28266827 DOI: 10.1021/acsami.6b13422
    Tissue engineering aims to generate or facilitate regrowth or healing of damaged tissues by applying a combination of biomaterials, cells, and bioactive signaling molecules. In this regard, growth factors clearly play important roles in regulating cellular fate. However, uncontrolled release of growth factors has been demonstrated to produce severe side effects on the surrounding tissues. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) incorporated three-dimensional (3D) CORAGRAF scaffolds were engineered to achieve controlled release of platelet-derived growth factor-BB (PDGF-BB) for the differentiation of stem cells within the 3D polymer network. Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and microtomography were applied to characterize the fabricated scaffolds. In vitro study revealed that the CORAGRAF-PLGA-PDGF-BB scaffold system enhanced the release of PDGF-BB for the regulation of cell behavior. Stromal cell attachment, viability, release of osteogenic differentiation markers such as osteocalcin, and upregulation of osteogenic gene expression exhibited positive response. Overall, the developed scaffold system was noted to support rapid cell expansion and differentiation of stromal cells into osteogenic cells in vitro for bone tissue engineering applications.
  19. Vedanthan R, Bernabe-Ortiz A, Herasme OI, Joshi R, Lopez-Jaramillo P, Thrift AG, et al.
    Cardiol Clin, 2017 Feb;35(1):99-115.
    PMID: 27886793 DOI: 10.1016/j.ccl.2016.08.010
    Elevated blood pressure, a major risk factor for ischemic heart disease, heart failure, and stroke, is the leading global risk for mortality. Treatment and control rates are very low in low- and middle-income countries. There is an urgent need to address this problem. The Global Alliance for Chronic Diseases sponsored research projects focus on controlling hypertension, including community engagement, salt reduction, salt substitution, task redistribution, mHealth, and fixed-dose combination therapies. This paper reviews the rationale for each approach and summarizes the experience of some of the research teams. The studies demonstrate innovative and practical methods for improving hypertension control.
  20. Iman V, Mohan S, Abdelwahab SI, Karimian H, Nordin N, Fadaeinasab M, et al.
    Drug Des Devel Ther, 2017;11:103-121.
    PMID: 28096658 DOI: 10.2147/DDDT.S115135
    Therapy that directly targets apoptosis and/or inflammation could be highly effective for the treatment of cancer. Murraya koenigii is an edible herb that has been traditionally used for cancer treatment as well as inflammation. Here, we describe that girinimbine, a carbazole alkaloid isolated from M. koenigii, induced apoptosis and inhibited inflammation in vitro as well as in vivo. Induction of apoptosis in human colon cancer cells (HT-29) by girinimbine revealed decreased cell viability in HT-29, whereas there was no cytotoxic effect on normal colon cells. Changes in mitochondrial membrane potential, nuclear condensation, cell permeability, and cytochrome c translocation in girinimbine-treated HT-29 cells demonstrated involvement of mitochondria in apoptosis. Early-phase apoptosis was shown in both acridine orange/propidium iodide and annexin V results. Girinimbine treatment also resulted in an induction of G0/G1 phase arrest which was further corroborated with the upregulation of two cyclin-dependent kinase proteins, p21 and p27. Girinimbine treatment activated apoptosis through the intrinsic pathway by activation of caspases 3 and 9 as well as cleaved caspases 3 and 9 which ended by triggering the execution pathway. Moreover, apoptosis was confirmed by downregulation of Bcl-2 and upregulation of Bax in girinimbine-treated cells. In addition, the key tumor suppressor protein, p53, was seen to be considerably upregulated upon girinimbine treatment. Induction of apoptosis by girinimbine was also evidenced in vivo in zebrafish embryos, with results demonstrating significant distribution of apoptotic cells in embryos after a 24-hour treatment period. Meanwhile, anti-inflammatory action was evidenced by the significant dose-dependent girinimbine inhibition of nitric oxide production in lipopolysaccharide/interferon-gamma-induced cells along with significant inhibition of nuclear factor-kappa B translocation from the cytoplasm to nucleus in stimulated RAW 264.7 cells. Girinimbine was also shown to have considerable antioxidant activity whereby 20 μg/mL of girinimbine was equivalent to 82.17±1.88 μM of Trolox. In mice with carrageenan-induced peritonitis, oral pretreatment with girinimbine helped limit total leukocyte migration (mainly of neutrophils), and reduced pro-inflammatory cytokine levels (interleukin-1beta and tumor necrosis factor-alpha) in the peritoneal fluid. These findings strongly suggest that girinimbine could act as a chemopreventive and/or chemotherapeutic agent by inducing apoptosis while suppressing inflammation. There is a potential for girinimbine to be further investigated for its applicability in treating early stages of cancer.
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