Displaying publications 1 - 20 of 87 in total

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  1. Structure and function of proprotein convertase subtilisin/kexin type 9 (PCSK9) in atherosclerosis
    Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019 Feb 14.
    PMID: 30767742 DOI: 10.2174/1389450120666190214141626
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  2. Recent Advances in Rational Diagnosis and Treatment of Normal Pressure Hydrocephalus: A Critical Appraisal on Novel Diagnostic, Therapy Monitoring and Treatment Modalities
    Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019;20(10):1041-1057.
    PMID: 30767741 DOI: 10.2174/1389450120666190214121342
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  3. A study exploring the association of attitude and treatment satisfaction with glycaemic level among gestational diabetes mellitus patients
    Hussain Z, Yusoff ZM, Sulaiman SA
    Prim Care Diabetes, 2015 Aug;9(4):275-82.
    PMID: 25457621 DOI: 10.1016/j.pcd.2014.10.002
    AIMS: The aim of this study was to evaluate attitude and treatment satisfaction of women suffering from GDM and their association with glycaemic level.
    METHODS: A cross sectional study was conducted in antenatal clinic of Hospital Pulau Pinang, Malaysia from June to December 2013 on the sample of 175 patients. Data was collected through modified version of Diabetes Integration Scale (ATT-19) and Diabetes Treatment Satisfaction Questionnaires (DSTQs). Glycaemic level was evaluated in terms of Fasting Plasma Glucose (FPG). Three most recent values of FPG (mmol/l) were taken from patients medical profiles and their mean was calculated. Descriptive and inferential statistics were used for data analysis.
    RESULTS: A total of 166 patients were included in final analysis. Only 35 (21.1%) patients had positive attitude and 122 (73.5%) of patients had adequate treatment satisfaction. There was no significant association of total mean ATT-19 score with age, ethnicity, educational level, occupational status, family history and type of therapy. For treatment satisfaction statistically significant association was present only between total mean treatment satisfaction score and educational level. Patients with negative attitude and inadequate treatment satisfaction had higher mean glycaemic level.
    CONCLUSIONS: It is concluded that more than two folds of patients were satisfied with their ongoing treatment but majority of the patients were feeling difficulty in active coping measures for the management of GDM.
    KEYWORDS: Attitude; GDM; Glycaemic level; Treatment satisfaction

    Study site: antenatal clinic of Hospital Pulau Pinang
  4. Evaluation of knowledge regarding gestational diabetes mellitus and its association with glycaemic level: A Malaysian study
    Hussain Z, Yusoff ZM, Sulaiman SA
    Prim Care Diabetes, 2015 Jun;9(3):184-90.
    PMID: 25132140 DOI: 10.1016/j.pcd.2014.07.007
    AIMS: The aim of this study was to evaluate the knowledge about GDM and its corresponding relation with glycaemic level in GDM patients.
    METHOD: A cross-sectional study was conducted in antenatal clinic of Hospital Pulau Pinang, Malaysia from June 2013 to December 2013 using Gestational Diabetes Mellitus Knowledge Questionnaire (GDMKQ) on the sample of 175 GDM patients. Three most recent fasting plasma glucose (FPG) values (mmol/l) were taken from patients profiles and mean was calculated.
    RESULTS: A total of 166 patients were included in final analysis. A total mean knowledge score of 166 patients was 10.01±3.63 and total mean FPG value was 5.50±1.13. Knowledge had a significant negative association with FPG (r=- 0.306, P<0.01). Among different knowledge domains, highest mean score was seen for diet/food values domain and lowest for management of GDM. Educational level seems to be the most significant predictor of GDM knowledge and glycaemic control. Highest mean knowledge score and lowest mean glycaemic levels were recorded for patients aged 25-29 years, Malay ethnicity, working women and family history of DM.
    CONCLUSION: Higher Knowledge about GDM is related to better glycaemic control. New educational strategies should be developed to improve the lower health literacy.
    KEYWORDS: Educational level; GDM; Glycaemic level; Knowledge

    Study site: antenatal clinic of Hospital Pulau Pinang, Malaysia
  5. Comparative susceptibility studies of clinically isolated Pseudomonas aeruginosa, Escherichia coli and Klebsiella spp to cefoperazone and cefotaxime
    Lee YH, Hussain ZA, Choong FP
    J Hyg Epidemiol Microbiol Immunol, 1990;34(3):299-303.
    PMID: 2125616
    The in-vitro activity of cefotaxime and cefoperazone were compared using clinically isolated Escherichia coli, Klebsiella spp and Pseudomonas aeruginosa. Cefotaxime was found on a weight to weight basis, to be much more active than cefoperazone. All the three species studied show the presence of cefoperazone-resistant population which were sensitive to cefotaxime. The possible mechanisms of resistance to these antibiotics were discussed.
  6. Fulltext Association of Commercial Rice Varieties with Weedy Rice Accessions (Oryza sativa complex) in Pulau Pinang's Rice Granary Area
    Hussain Z, Man A, Othman AS
    Trop Life Sci Res, 2011 Dec;22(2):1-11.
    PMID: 24575213 MyJurnal
    Weedy rice (WR) is the most significant weed in direct-seeded fields. It has morphological characteristics similar to those of cultivated rice varieties. WR is more difficult to control than other weeds. We collected WR accessions from four sites within the Pulau Pinang rice growing areas. Thirty six different accessions were collected from each site: B, the northern site; P, the central site; A, the southern site; and N, the southwestern site. Wild rice (Oryza rufipogon), which grows in the sampled areas, was also collected together with four varieties (MR84, MR185, MR211 and MR219) that have been widely planted in these areas for a long period of time. The objective of this study was to compare the morphological characteristics of the WR accessions and cultivated rice. Twenty characteristics were observed for the comparison of WR accessions and rice cultivars. Morpho-matrix analyses allowed the specimens to be grouped to two main groups (A and B), based on a 95% dissimilarity matrix. Group A was subdivided into 7 subgroups consisting of a few WR accessions, wild rice and MR211 (control), and group B was subdivided to 10 subgroups consisting of other WR accessions and the 3 other control varieties. Dendrogram analysis indicated that the morphological traits used in this study were able to differentiate among the WR accessions and the cultivars, except for rice cultivar MR211 and WRA8, which grouped together in subgroup A2. STRUCTURE program analysis indicated that all individuals were distinguishable and were divided into 18 clusters. These results suggest that some genes of the WR accessions have been influenced by commercial varieties. The information gained from this study will be useful to develop rice weed management protocols and good agricultural practices to control WR in the future.
  7. New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects
    Ei Thu H, Hussain Z, Shuid AN
    Curr Drug Targets, 2018;19(8):865-876.
    PMID: 27894237 DOI: 10.2174/1389450117666161125174625
    Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.
  8. Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy
    Zhuo F, Abourehab MAS, Hussain Z
    Carbohydr Polym, 2018 Oct 01;197:478-489.
    PMID: 30007638 DOI: 10.1016/j.carbpol.2018.06.023
    Nano-delivery systems have gained remarkable recognition for targeted delivery of therapeutic payload, reduced off-target effects, and improved biopharmaceutical profiles of drugs. Therefore, we aimed to fabricate polymeric nanoparticles (NPs) to deliver tacrolimus (TCS) to deeper layers of the skin in order to alleviate its systemic toxicity and improved therapeutic efficacy against atopic dermatitis (AD). To further optimize the targeting efficiency, TCS-loaded NPs were coated with hyaluronic acid (HA). Following the various physicochemical optimizations, the prepared HA-TCS-CS-NPs were tested for in vitro drug release kinetics, drug permeation across the stratum corneum, percentage of drug retained in the epidermis and dermis, and anti-AD efficacy. Results revealed that HA-TCS-CS-NPs exhibit sustained release profile, promising drug permeation ability, improved skin retention, and pronounced anti-AD efficacy. Conclusively, we anticipated that HA-based modification of TCS-CS-NPs could be a promising therapeutic approach for rationalized management of AD, particularly in children as well as in adults having steroid phobia.
  9. Dual infective burden of Helicobacter pylori and intestinal parasites: Good or bad news for the host?
    Hussain Z, El-Omar E, Lee YY
    Indian J Gastroenterol, 2020 04;39(2):111-116.
    PMID: 32372188 DOI: 10.1007/s12664-020-01045-8
  10. Phytomedicines are Efficient Complementary Therapies for the Treatment of Atopic Dermatitis: A Review of Mechanistic Insight and Recent Updates
    Tumpang MA, Ramli NA, Hussain Z
    Curr Drug Targets, 2018;19(6):674-700.
    PMID: 28914203 DOI: 10.2174/1389450118666170913162147
    BACKGROUND: Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD.

    OBJECTIVE: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy.

    RESULTS: The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies.

    CONCLUSION: In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents.

  11. Fulltext Human Hand Motion Analysis during Different Eating Activities
    Hussain Z, Zainul Azlan N, Yusof AZB
    Appl Bionics Biomech, 2018;2018:8567648.
    PMID: 29515649 DOI: 10.1155/2018/8567648
    The focus of this research is to analyse both human hand motion and force, during eating, with respect to differing food characteristics and cutlery (including a fork and a spoon). A glove consisting of bend and force sensors has been used to capture the motion and contact force exerted by fingers during different eating activities. The Pearson correlation coefficient has been used to show that a significant linear relationship exists between the bending motion of the fingers and the forces exerted during eating. Analysis of variance (ANOVA) and independent samplest-tests are performed to establish whether the motion and force exerted by the fingers while eating is influenced by the different food characteristics and cutlery. The middle finger motion showed the least positive correlation with index fingertip and thumb-tip force, irrespective of the food characteristics and cutlery used. The ANOVA andt-test results revealed that bending motion of the index finger and thumb varies with respect to differing food characteristics and the type of cutlery used (fork/spoon), whereas the bending motion of the middle finger remains unaffected. Additionally, the contact forces exerted by the thumb tip and index fingertip remain unaffected with respect to differing food types and cutlery used.
  12. Intelligent medical disease diagnosis using improved hybrid genetic algorithm--multilayer perceptron network
    Ahmad F, Isa NA, Hussain Z, Osman MK
    J Med Syst, 2013 Apr;37(2):9934.
    PMID: 23479268 DOI: 10.1007/s10916-013-9934-7
    An improved genetic algorithm procedure is introduced in this work based on the theory of the most highly fit parents (both male and female) are most likely to produce healthiest offspring. It avoids the destruction of near optimal information and promotes further search around the potential region by encouraging the exchange of highly important information among the fittest solution. A novel crossover technique called Segmented Multi-chromosome Crossover is also introduced. It maintains the information contained in gene segments and allows offspring to inherit information from multiple parent chromosomes. The improved GA is applied for the automatic and simultaneous parameter optimization and feature selection of multi-layer perceptron network in medical disease diagnosis. Compared to the previous works, the average accuracy of the proposed algorithm is the best among all algorithms for diabetes and heart dataset, and the second best for cancer dataset.
  13. Nanomedicines for improved targetability to inflamed synovium for treatment of rheumatoid arthritis: Multi-functionalization as an emerging strategy to optimize therapeutic efficacy
    Fang G, Zhang Q, Pang Y, Thu HE, Hussain Z
    J Control Release, 2019 06 10;303:181-208.
    PMID: 31015032 DOI: 10.1016/j.jconrel.2019.04.027
    Owing to its intricate autoimmune pathophysiology and significant risks of progression to other rheumatic co-morbidities (i.e., osteoporosis and osteoarthritis), a plausible therapeutic regimen is mandatory for early-stage management of rheumatoid arthritis (RA). Nevertheless, the conventional therapeutic agents particularly the corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) have shown grander success in the treatment of RA; however, long-term use of these agents is also associated with serious adverse events. To combat these issues and optimize therapeutic efficacy, nanotechnology-based interventions have been emerged as viable option. While, nanomedicines signposted superiority over the conventional pharmacological moieties; there are still many pharmacokinetic and pharmacodynamic challenges to nanomedicines following their intravenous or intra-articular administration. To circumvent these challenges, significant adaptations such as PEGylation, surface conjugation of targeting ligand(s), and site- responsive behavior (i.e., pH-, biochemical-, or thermal-responsiveness) have been implemented. Besides, multi-functionalization of nanomedicines has been emerging as an exceptional strategy to overcome pharmacokinetic challenges, improve targetability to inflamed synovium, maximise internalisation into the activated macrophages, and improved therapeutic outcomes for treatment of RA. Therefore, this review aims to conceptualize and recapitulate the substantial evidences regarding the pharmacokinetic and pharmacodynamic superiority of multi-functionalized nanomedicines over the naked nanomedicines for site-selective targeting to inflamed synovium and rational treatment of RA and other rheumatic co-morbidities. Pharmaceutical sustainability of the multi-functionalized nanomedicines for improved biocompatibility, profound interaction with the targeting tissue/cells/sub-cellular domain, and diminished systemic toxicity has also been pondered.
  14. Fulltext Crystal structure of tetra-aqua-bis(3,5-di-amino-4H-1,2,4-triazol-1-ium)cobalt(II) bis-[bis-(pyridine-2,6-di-carboxyl-ato)cobaltate(II)] dihydrate
    Johnson A, Mbonu J, Hussain Z, Loh WS, Fun HK
    Acta Crystallogr E Crystallogr Commun, 2015 Jun 1;71(Pt 6):m139-40.
    PMID: 26090171 DOI: 10.1107/S2056989015010014
    The asymmetric unit of the title compound, [Co(C2H6N5)2(H2O)4][Co(C7H3NO4)2]2·2H2O, features 1.5 Co(II) ions (one anionic complex and one half cationic complex) and one water mol-ecule. In the cationic complex, the Co(II) atom is located on an inversion centre and is coordinated by two triazolium cations and four water mol-ecules, adopting an octa-hedral geometry where the N atoms of the two triazolium cations occupy the axial positions and the O atoms of the four water mol-ecules the equatorial positions. The two triazole ligands are parallel offset (with a distance of 1.38 Å between their planes). In the anionic complex, the Co(II) ion is six-coordinated by two N and four O atoms of the two pyridine-2,6-di-carboxyl-ate anions, exhibiting a slightly distorted octa-hedral coordination geometry in which the mean plane of the two pyridine-2,6-di-carboxyl-ate anions are almost perpendicular to each other, making a dihedral angle of 85.87 (2)°. In the crystal, mol-ecules are linked into a three-dimensional network via C-H⋯O, C-H⋯N, O-H⋯O and N-H⋯O hydrogen bonds.
  15. Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: fabrication, characterization, and cellular and molecular evidences of enhanced bone regeneration
    Dong J, Tao L, Abourehab MAS, Hussain Z
    Int J Biol Macromol, 2018 Sep;116:1268-1281.
    PMID: 29782984 DOI: 10.1016/j.ijbiomac.2018.05.116
    Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis.
  16. Polymeric nanoparticles for topical delivery of alpha and beta arbutin: preparation and characterization
    Ayumi NS, Sahudin S, Hussain Z, Hussain M, Samah NHA
    Drug Deliv Transl Res, 2019 04;9(2):482-496.
    PMID: 29569027 DOI: 10.1007/s13346-018-0508-6
    To investigate the use of chitosan nanoparticles (CS-TPP-NPs) as carriers for α- and β-arbutin. In this study, CS-TPP-NPs containing α- and β-arbutin were prepared via the ionic cross-linking of CS and TPP and characterized for particle size, zeta potential, and dispersity index. The entrapment efficiency and loading capacity of various β-arbutin concentrations (0.1, 0.2, 0.4, 0.5, and 0.6%) were also investigated. SEM, TEM FTIR, DSC and TGA analyses of the nanoparticles were performed to further characterize the nanoparticles. Finally, stability and release studies were undertaken to ascertain further the suitability of the nanoparticles as a carrier system for α- and β-arbutin. Data obtained clearly indicates the potential for use of CS-TPP-NPs as a carrier for the delivery of α- and β-arbutin. The size obtained for the alpha nanoparticles (α-arbutin CSNPs) ranges from 147 to 274 d.nm, with an increase in size with increasing alpha arbutin concentration. β-arbutin nanoparticles (β-arbutin CSNPs) size range was from 211.1 to 284 dn.m. PdI for all nanoparticles remained between 0.2-0.3 while the zeta potential was between 41.6-52.1 mV. The optimum encapsulation efficiency and loading capacity for 0.4% α-arbutin CSNPs were 71 and 77%, respectively. As for β-arbutin, CSNP optimum encapsulation efficiency and loading capacity for 0.4% concentration were 68 and 74%, respectively. Scanning electron microscopy for α-arbutin CSNPs showed a more spherical shape compared to β-arbutin CSNPs where rod-shaped particles were observed. However, under transmission electron microscopy, the shapes of both α- and β-arbutin CSNP nanoparticles were spherical. The crystal phase identification of the studied samples was carried out using X-ray diffraction (XRD), and the XRD of both α and β-arbutin CSNPs showed to be more crystalline in comparison to their free form. FTIR spectra showed intense characteristic peaks of chitosan appearing at 3438.3 cm-1 (-OH stretching), 2912 cm-1 (-CH stretching), represented 1598.01 cm-1 (-NH2) for both nanoparticles. Stability studies conducted for 90 days revealed that both α- and β-arbutin CSNPs were stable in solution. Finally, release studies of both α- and β-arbutin CSNPs showed a significantly higher percentage release in comparison to α- and β-arbutin in their free form. Chitosan nanoparticles demonstrate considerable promise as a carrier system for α- and β-arbutin, the use of which is anticipated to improve delivery of arbutin through the skin, in order to improve its efficacy as a whitening agent.
  17. Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts
    Thu HE, Mohamed IN, Hussain Z, Shuid AN
    J Ethnopharmacol, 2017 Jan 04;195:143-158.
    PMID: 27818256 DOI: 10.1016/j.jep.2016.10.085
    ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats.

    AIM OF THE STUDY: To evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone.

    MATERIALS AND METHODS: Cell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis.

    RESULTS: The cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL.

    CONCLUSION: Compared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

  18. Eurycoma longifolia, A Potential Phytomedicine for the Treatment of Cancer: Evidence of p53-mediated Apoptosis in Cancerous Cells
    Thu HE, Hussain Z, Mohamed IN, Shuid AN
    Curr Drug Targets, 2018;19(10):1109-1126.
    PMID: 28721818 DOI: 10.2174/1389450118666170718151913
    BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent antiproliferative and anticancer efficacy against various types of human cancers.

    OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells.

    RESULTS: Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced.

    CONCLUSION: Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.

  19. Recent Advances in Polymer-based Wound Dressings for the Treatment of Diabetic Foot Ulcer: An Overview of State-of-the-art
    Hussain Z, Thu HE, Shuid AN, Katas H, Hussain F
    Curr Drug Targets, 2018;19(5):527-550.
    PMID: 28676002 DOI: 10.2174/1389450118666170704132523
    BACKGROUND: Diabetic foot ulcers (DFUs) are the chronic, non-healing complications of diabetic mellitus which compels a significant burden to the patients and the healthcare system. Peripheral vascular disease, diabetic neuropathy, and abnormal cellular and cytokine/chemokine activity are among the prime players which exacerbate the severity and prevent wound repair. Unlike acute wounds, DFUs impose a substantial challenge to the conventional wound dressings and demand the development of novel and advanced wound healing modalities. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, eliminate wound exudate and stimulate tissue regeneration.

    OBJECTIVE: To date, numerous conventional wound dressings are employed for the management of DFUs but there is a lack of absolute and versatile choice. The current review was therefore aimed to summarize and critically discuss the available evidences related to pharmaceutical and therapeutic viability of polymer-based dressings for the treatment of DFUs.

    RESULTS: A versatile range of naturally-originated polymers including chitosan (CS), hyaluronic acid (HA), cellulose, alginate, dextran, collagen, gelatin, elastin, fibrin and silk fibroin have been utilized for the treatment of DFUs. These polymers have been used in the form of hydrogels, films, hydrocolloids, foams, membranes, scaffolds, microparticles, and nanoparticles. Moreover, the wound healing viability and clinical applicability of various mutually modified, semi-synthetic or synthetic polymers have also been critically discussed.

    CONCLUSION: In summary, this review enlightens the most recent developments in polymer-based wound dressings with special emphasis on advanced polymeric biomaterials, innovative therapeutic strategies and delivery approaches for the treatment of DFUs.

  20. Efficient Colonic Delivery of DsiRNA by Pectin-Coated Polyelectrolyte Complex Nanoparticles: Preparation, Characterization and Improved Gastric Survivability
    Hussain Z, Katas H, Yan SL, Jamaludin D
    Curr Drug Deliv, 2017;14(7):1016-1027.
    PMID: 28240178 DOI: 10.2174/1567201814666170224142446
    BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments.

    OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer.

    METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu.

    RESULTS: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to -6.2 ± 2.7 mV respectively, when the concentrations of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF) evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery.

    CONCLUSION: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.

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