Publications by authors named "Siew Hua Gan"

158 Publications

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies.

Front Pharmacol 2021 3;12:629935. Epub 2021 May 3.

Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto, Nigeria.

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.
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http://dx.doi.org/10.3389/fphar.2021.629935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126690PMC
May 2021

Burden of stroke in the Kingdom of Saudi Arabia: A soaring epidemic.

Saudi Pharm J 2021 Mar 12;29(3):264-268. Epub 2021 Feb 12.

Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakaka, Saudi Arabia.

Stroke is a key cerebrovascular disease that is related to high morbidity and mortality in the globe. The Kingdom of Saudi Arabia (KSA) is not an exception where stroke is fast developing into a serious challenge due to the high mortality rate. Additionally, stroke presents a tremendous economic burden and has a devastating effect on the quality of lives of individuals. The number of stroke cases are increasing yearly, thus posing a major challenge to the health care system. Therefore, it is crucial to implement primary and secondary prevention strategies in the KSA. Nevertheless, as compared with developed countries, information on the prevalence, socio-demographic properties and prevention of stroke remains scarce that could be attributed to the shortage of research conducted in this specified region. The review is written to address the various aspects of stroke in the KSA, based on current literatures search using PubMed, Scopus, Web of Science and Google Scholar databases, to identify studies published since inception to Dec 2020.
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http://dx.doi.org/10.1016/j.jsps.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084724PMC
March 2021

Mapping the role of pH-adjusted potassium in diabetic ketoacidosis: Hypokalemia and the patient outcomes.

Int J Clin Pract 2021 May 2:e14315. Epub 2021 May 2.

School of Pharmacy, Monash University Malaysia, Selangor, Malaysia.

Background: Incidence of hypokalemia during management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment.

Aims: We aimed to find the role of pH in development of hypokalemia, and their mutual impact on patient outcomes during DKA management.

Methodology: Adult DKA patient's admission-data of preceding three years (2015-2017) was retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (in hours), severity of hypokalemia, and hospitalization length (days). Linear regression was used to determine significant associations/predictors.

Results: The study was concluded on 85 patients. Hypokalemia was observed in nearly three-fourths of all admissions and occurred by the time of ED care termination. Each one mmol/L increase in pH significantly 1) reduced degree of hypokalemia by 0.07 mmol/L, 2) delayed time to develop hypokalemia by 4.58 hours, 3) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each one mmol/L reduction in degree of hypokalemia increased hospitalization length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalization length by 0.01 days.

Conclusion: pH-adjusted potassium (pH ) shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measure serum potassium in DKA. Utilizing pH will help to avoid hypokalemia, reduce its severity, and shorten ED care which will subsequently reduce hospitalization length. We expect pH to improve pharmacoeconomics in future.
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http://dx.doi.org/10.1111/ijcp.14315DOI Listing
May 2021

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma.

PLoS One 2021 30;16(3):e0249091. Epub 2021 Mar 30.

School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249091PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009377PMC
March 2021

Re-visiting pH-adjusted potassium to avoid hypokalemic crisis during management of diabetic ketoacidosis: A conceptual framework.

Diabetes Metab Syndr 2021 Mar-Apr;15(2):573-580. Epub 2021 Mar 5.

School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. Electronic address:

Background And Aims: Diabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (S) drops within normal range, and to withhold insulin if S is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA.

Methods: Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia.

Results: Acidosis affects S and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing S level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated.

Conclusion: In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.
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http://dx.doi.org/10.1016/j.dsx.2021.03.001DOI Listing
March 2021

Prevalence of Drug-Related Problems and Complementary and Alternative Medicine Use in Malaysia: A Systematic Review and Meta-Analysis of 37,249 Older Adults.

Pharmaceuticals (Basel) 2021 Feb 25;14(3). Epub 2021 Feb 25.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.

Drug-related problems (DRPs) in the elderly include polypharmacy, potentially inappropriate medications, nonadherence, and drug-related falls. In this systematic review and meta-analysis, the prevalence of DRPs and complementary and alternative medicine (CAM) use among the Malaysian elderly was estimated. PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify studies published since their inception up to 24 August 2020. A random-effects model was used to generate the pooled prevalence of DRPs along with its corresponding 95% confidence interval (CI). The heterogeneity of the results was estimated using the statistics, and Cochran's Q test and sensitivity analyses were performed to confirm the robustness of the results. We identified 526 studies, 23 of which were included in the meta-analysis. ( = 29,342). The pooled prevalence of DRPs among Malaysian elderly was as follows: (1) polypharmacy: 49.5% [95% CI: 20.5-78.6], (2) potentially inappropriate medications: 28.9% [95% CI: 25.4-32.3], (3) nonadherence to medications: 60.6% [95% CI: 50.2-70.9], and (4) medication-related falls 39.3% [95% CI: 0.0-80.8]. Approximately one in two Malaysian elderly used CAM. The prevalence of polypharmacy and potentially inappropriate medications among the Malaysian elderly population was high, calling for measures and evidence-based guidelines to ensure the safe medication use.
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http://dx.doi.org/10.3390/ph14030187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996557PMC
February 2021

Protective Effect of Natural Products against Huntington's Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action.

ACS Chem Neurosci 2021 02 21;12(3):391-418. Epub 2021 Jan 21.

Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, 47500 Selangor, Malaysia.

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against / models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either or models were included in the present review. Behavioral outcomes in the HD model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
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http://dx.doi.org/10.1021/acschemneuro.0c00824DOI Listing
February 2021

Protective effect of mangiferin on memory impairment: A systematic review.

Saudi J Biol Sci 2021 Jan 13;28(1):917-927. Epub 2020 Nov 13.

Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université De Paris, Paris, France.

Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient's cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12-154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.
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http://dx.doi.org/10.1016/j.sjbs.2020.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783829PMC
January 2021

Nutritional Composition and Bioactive Compounds in Tomatoes and Their Impact on Human Health and Disease: A Review.

Foods 2020 Dec 26;10(1). Epub 2020 Dec 26.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor 47500, Malaysia.

Tomatoes are consumed worldwide as fresh vegetables because of their high contents of essential nutrients and antioxidant-rich phytochemicals. Tomatoes contain minerals, vitamins, proteins, essential amino acids (leucine, threonine, valine, histidine, lysine, arginine), monounsaturated fatty acids (linoleic and linolenic acids), carotenoids (lycopene and β-carotenoids) and phytosterols (β-sitosterol, campesterol and stigmasterol). Lycopene is the main dietary carotenoid in tomato and tomato-based food products and lycopene consumption by humans has been reported to protect against cancer, cardiovascular diseases, cognitive function and osteoporosis. Among the phenolic compounds present in tomato, quercetin, kaempferol, naringenin, caffeic acid and lutein are the most common. Many of these compounds have antioxidant activities and are effective in protecting the human body against various oxidative stress-related diseases. Dietary tomatoes increase the body's level of antioxidants, trapping reactive oxygen species and reducing oxidative damage to important biomolecules such as membrane lipids, enzymatic proteins and DNA, thereby ameliorating oxidative stress. We reviewed the nutritional and phytochemical compositions of tomatoes. In addition, the impacts of the constituents on human health, particularly in ameliorating some degenerative diseases, are also discussed.
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http://dx.doi.org/10.3390/foods10010045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823427PMC
December 2020

A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols.

Oxid Med Cell Longev 2020 23;2020:8878172. Epub 2020 Nov 23.

Department of Community and Family Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, 88400 Sabah, Malaysia.

Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world's most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights.
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http://dx.doi.org/10.1155/2020/8878172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704201PMC
June 2021

Pharmacist-led counselling intervention to improve antiretroviral drug adherence in Pakistan: a randomized controlled trial.

BMC Infect Dis 2020 Nov 23;20(1):874. Epub 2020 Nov 23.

Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan.

Background: Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH).

Methods: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire.

Results: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p < 0.0001).

Conclusions: The findings support the improvement in ART adherence and HIV management.

Trial Registration: The trial is registered with Australian New Zealand Clinical Trials Registry ( ACTRN12618001882213 ). Registered 20 November 2018.
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http://dx.doi.org/10.1186/s12879-020-05571-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684945PMC
November 2020

Potentials and Safety of Date Palm Fruit against Diabetes: A Critical Review.

Foods 2020 Oct 28;9(11). Epub 2020 Oct 28.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.

Diabetes is a chronic metabolic disorder triggered by disturbances in carbohydrate, protein, and lipid metabolisms, where either reduced secretion or sensitivity of insulin is observed coupled with poor glucose control. Date palm fruits are one of the fruits reported to have good potential in diabetes treatment due to its presence of polyphenols exerting strong antioxidant activities. Other possible mechanisms of action include the polyphenolic compounds, which can inhibit enzymes like α-amylase and α-glucosidase. Flavonoids in dates can stimulate β-cells by increasing the number of islets and β-cells, recovering endocrine pancreatic tissues, reducing β-cell apoptosis, activating insulin receptors following the increase in insulin secretion, in addition to improving diabetes-induced complications. In this review, the in vitro, in vivo, and human study-based evidence of date palm as an anti-diabetic fruit is summarised.
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http://dx.doi.org/10.3390/foods9111557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693939PMC
October 2020

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells.

Pharmaceutics 2020 Oct 18;12(10). Epub 2020 Oct 18.

Tropical Medicine and Biology Multidisciplinary Platform, Monash University, Jalan Lagoon Selatan, Bandar Sunway 47500, Petaling Jaya, Selangor, Malaysia.

Background: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release.

Methods: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines.

Results: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and -20 °C and when placed at a temperature of 37 °C.

Conclusions: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.
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http://dx.doi.org/10.3390/pharmaceutics12100984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589039PMC
October 2020

Prevalence of Antibiotic-Resistant Pulmonary Tuberculosis in Bangladesh: A Systematic Review and Meta-Analysis.

Antibiotics (Basel) 2020 Oct 17;9(10). Epub 2020 Oct 17.

Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia.

Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5-57.1], 14.3% [95% CI: 11.4-17.2], 22.2% [95% CI: 18.8-25.7], 7.7% [95% CI: 5.6-9.7], and 0.3% [95% CI: 0.0-1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended.
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http://dx.doi.org/10.3390/antibiotics9100710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602942PMC
October 2020

Screening of 22q11.2DS Using Multiplex Ligation-Dependent Probe Amplification as an Alternative Diagnostic Method.

Biomed Res Int 2020 28;2020:6945730. Epub 2020 Sep 28.

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Background: The 22q11.2 deletion syndrome (22q11.2DS) is the most common form of deletion disorder in humans. Low copy repeats flanking the 22q11.2 region confers a substrate for nonallelic homologous recombination (NAHR) events leading to rearrangements which have been reported to be associated with highly variable and expansive phenotypes. The 22q11.2DS is reported as the most common genetic cause of congenital heart defects (CHDs).

Methods: A total of 42 patients with congenital heart defects, as confirmed by echocardiography, were recruited. Genetic molecular analysis using a fluorescence hybridization (FISH) technique was conducted as part of routine 22q11.2DS screening, followed by multiplex ligation-dependent probe amplification (MLPA), which serves as a confirmatory test.

Results: Two of the 42 CHD cases (4.76%) indicated the presence of 22q11.2DS, and interestingly, both cases have conotruncal heart defects. In terms of concordance of techniques used, MLPA is superior since it can detect deletions within the 22q11.2 locus and outside of the typically deleted region (TDR) as well as duplications.

Conclusion: The incidence of 22q11.2DS among patients with CHD in the east coast of Malaysia is 0.047. MLPA is a scalable and affordable alternative molecular diagnostic method in the screening of 22q11.2DS and can be routinely applied for the diagnosis of deletion syndromes.
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http://dx.doi.org/10.1155/2020/6945730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539069PMC
May 2021

Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells.

Int J Mol Sci 2020 Sep 14;21(18). Epub 2020 Sep 14.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia.

: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. : In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. : The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.
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http://dx.doi.org/10.3390/ijms21186721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555837PMC
September 2020

Clinical and genetic risk factors for new-onset diabetes mellitus after transplantation (NODAT) in major transplant centres in Malaysia.

BMC Nephrol 2020 09 7;21(1):388. Epub 2020 Sep 7.

Division of Nephrology, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.

Background: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

Methods: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

Results: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

Conclusion: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.
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http://dx.doi.org/10.1186/s12882-020-02052-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487857PMC
September 2020

Prevalence and risk factors of prehypertension in university students in Sabah, Borneo Island of East Malaysia.

Medicine (Baltimore) 2020 May;99(21):e20287

Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.

Unhealthy lifestyle contributes mainly to an increased prevalence of non-communicable diseases including hypertension and cardiovascular diseases tend to increase in Malaysia. These diseases lead to an increased risk of end organ damage and cardiovascular complications. In this study, the prevalence of prehypertension and its associated risk factors among a cohort of university students in Sabah was determined.This is a prospective, cross-sectional study conducted among 365 undergraduate students irrespective of faculties at Universiti Malaysia Sabah (UMS). Standardized and validated World Health Organization (WHO) STEPS questionnaires were used to collect sociodemographic data. Additionally, clinical and anthropometric data were measured and recorded by a trained staff, followed by descriptive and logistic regression analyses.A total of 365 UMS undergraduate students aged 18 years and above participated in the study. The prevalence of prehypertension among university students was high (31%) (95% CI [29.1%, 34.3%]). Well-known risk factors for hypertension including family history of hypertension, reduced sleep duration, reduced physical activity, smoking, being overweight or obese were significantly associated with the risk of developing prehypertension (P < .05) among UMS students. However, no association was observed between ethnicity, age, and gender with prehypertension.A worryingly high percentage of UMS students are prehypertensive, indicating the need of early preventive strategies aimed at increasing awareness, early screening, and lifestyle modification to reduce the rising burden of the disease and the associated complications in this age group.
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http://dx.doi.org/10.1097/MD.0000000000020287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250021PMC
May 2020

Mutations in the tail domain of MYH3 contributes to atrial septal defect.

PLoS One 2020 21;15(4):e0230982. Epub 2020 Apr 21.

Human Genome Centre, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230982PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173802PMC
July 2020

Recent Advances in Diagnostic Approaches for Epstein-Barr Virus.

Pathogens 2020 Mar 18;9(3). Epub 2020 Mar 18.

Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.

Epstein-Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.
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http://dx.doi.org/10.3390/pathogens9030226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157745PMC
March 2020

Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension".

Int J Hypertens 2019;2019:2907675. Epub 2019 Oct 13.

School of Science and Health, Western Sydney University, NSW 2751, Australia.

[This corrects the article DOI: 10.1155/2019/6709817.].
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http://dx.doi.org/10.1155/2019/2907675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817927PMC
October 2019

Implication of Physiological and Biochemical Variables of Prognostic Importance in Lead Exposed Subjects.

Arch Environ Contam Toxicol 2020 Apr 16;78(3):329-336. Epub 2019 Oct 16.

Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.

The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5 years of outdoor experience and Hb levels < 10 µg/dl, and 100 traffic wardens with indoor duties were substituted in two groups. Levels of vitamins, cytokines, lead, iron, minerals, oxidative stress, and lipid peroxidation were estimated with help of their standard ELISA and spectrophotometric methods respectively. The present study show increased levels of lead in subjects (29.8 ± 3.8 vs. 1.5 ± 0.2 µg/dl) that may be involved in increasing oxidative stress, i.e., levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and isoprostanes were increased in subjects (4.6 ± 0.5, 4.3 ± 0.6 and 37.2 ± 5.1). Moreover, levels of antioxidants, i.e., superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were decreased. It also exhibits reduced levels of different enzymes in anemic traffic wardens. Current study concludes that wardens exposed to environmental lead are more susceptible to develop cardiovascular and neurological disorders. It shows that toxicity of lead maybe responsible for redox imbalance and production of proinflammatory cytokines. Thus, early detection of these biomarkers may help to reduce lead toxicity and it also may help to control the dilemma of uncontrolled environmental pollution by implicating strict actions against substandard gasoline.
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http://dx.doi.org/10.1007/s00244-019-00673-2DOI Listing
April 2020

Autoimmune disease and cancer comorbidity: Current understandings of immune-mediated pathogenesis and treatment.

Semin Cancer Biol 2020 08 4;64:iii-iv. Epub 2019 Oct 4.

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kota Bharu, Kelantan, Malaysia.

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http://dx.doi.org/10.1016/j.semcancer.2019.10.001DOI Listing
August 2020

Tualang honey ameliorates viral load, CD4 counts and improves quality of life in asymptomatic human immunodeficiency virus infected patients.

J Tradit Complement Med 2019 Oct 28;9(4):249-256. Epub 2018 Sep 28.

Pharmacology Department, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.

This is the first study to report on the effects of honey in asymptomatic HIV positive subjects in ameliorating CD4 count, viral load (VL) and quality of life (QOL). It is a randomized, controlled, open labelled study, comparing the effects of Tualang honey (TH) administration for six months at three different doses: 20 g (THL), 40 g (THI) or 60 g (THH) daily compared with control (no administered treatment, THC). Only asymptomatic HIV positive subjects (n=95) having CD4 count 250-600 cell/ml, not on antiretrovirals were enrolled. Blood, (together with QOL questionnaires administration) were investigated at baseline, three and six months (CD4 cell count) while VL was determined only at baseline and six months. Significant reductions in CD4 counts in THL and THC groups (p= 0.003 for both) were seen with no significant reductions in the CD4 counts in THI and THH groups (p=0.447 and 0.053 respectively). There was improvement in VL in THC and THI (130% and 32% respectively) and reductions in THL and THH (26% and 8% respectively). Within and between group analyses for VL indicated significant differences between THL and THH compared to THC. In addition, significant improvement in QOL of groups which received TH was noted. TH has the potential to improve the QOL (physical and psychological) and CD4 counts. There was a trend of lower VL in asymptomatic HIV subjects following TH administration thus supporting the possible role of TH in boosting the immune system by improving CD4 counts, causing VL reductions in HIV positive subjects.
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http://dx.doi.org/10.1016/j.jtcme.2018.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702152PMC
October 2019

Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo ( L. Osbeck) in Long Evan Rats.

J Toxicol 2019 10;2019:2529569. Epub 2019 Jun 10.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo ( L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), -glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.
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http://dx.doi.org/10.1155/2019/2529569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590546PMC
June 2019

In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model.

Drug Des Devel Ther 2019 6;13:1501-1513. Epub 2019 May 6.

Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.

In silico characterization can help to explain the interaction between molecules and predict three-dimensional structures. Various studies have confirmed the glucose-lowering effects of plant extracts, ie, lupeol and iso-orientin, which enable them to be used as antidiabetic agents. Aims of the present study were to evaluate the hypoglycemic activities of lupeol and iso-orientin in a rat model. The study proposed the effects of alloxan on blood glucose level, body weight, and oxidative stress. Thirty (n=30) Wistar albino rats were divided into six groups and were subjected to different combinations of the compounds. Levels of different stress markers, ie, malondialdehyde, superoxide dismutase, catalase, nitric oxide, glutathione, glutathione peroxide, glutathione reductase, and blood glucose levels were estimated with their respective methods. Whereas, for their in silico analysis, identified target proteins, GPR40, glucose-6-phosphatase, UCP2, glycogen phosphorylase, aldose reductase, and glucose transporter-4 were docked with lupeol and iso-orientin. Three-dimensional structures were predicted by ERRAT, Rampage, Verify3D, threading and homology approaches. Blood glucose levels were significantly increased in rats receiving intraperitoneal injection of alloxan (208±6.94 mg/dL) as compared to controls (90±7.38 mg/dL). Infected rats were administered plant extracts; combined treatment of both extracts (lupeol+iso-orientin) significantly reduced the levels of blood glucose (129.06±6.29 mg/dL) and improved the antioxidant status. Fifteen structures of each selected protein were evaluated using various techniques. Consequently, satisfactory quality factors [GPR40 (96.41%), glucose-6-phosphatase (96.56%), UCP2 (72.56%), glycogen phosphorylase (87.24%), aldose reductase (82.46%), and glucose transporter-4 (94.29%)] were selected. Molecular docking revealed interacting residues, effective drug properties and their binding affinities (ie, -8.9 to -12.6 Kcal/mol). Results of the study affirmed the antidiabetic activities of lupeol and iso-orientin. Administration of these extracts (either individually or in combination) significantly reduced blood glucose levels and oxidative stress. Hence, it may be considered beneficial in the treatment of diabetes.
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http://dx.doi.org/10.2147/DDDT.S176698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510393PMC
January 2020

Efficacy and Safety of Pioglitazone Monotherapy in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Sci Rep 2019 03 29;9(1):5389. Epub 2019 Mar 29.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia.

Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it's unique insulin sensitising action provides rationale to remain as a therapeutic option for managing type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis comparing pioglitazone monotherapy with monotherapies of other oral antidiabetic drugs for assessing its efficacy and safety in T2DM patients. Mean changes in glycated haemoglobin (HbA1c), and mean changes in fasting blood sugar (FBS) level, body weight (BW) and homeostasis model assessment-insulin resistance (HOMA-IR) were primary and secondary outcomes, respectively. Safety outcomes were changes in lipid parameters, blood pressure and incidences of adverse events. Metafor package of R software and RevMan software based on random-effects model were used for analyses. We included 16 randomised controlled trials. Pioglitazone monotherapy showed equivalent efficacy as comparators in reducing HbA1c by 0.05% (95% CI: -0.21 to 0.11) and greater efficacy in reducing FBS level by 0.24 mmol/l (95% CI: -0.48 to -0.01). Pioglitazone showed similar efficacy as comparators in reducing HOMA-IR (WMD: 0.05, 95% CI: -0.49 to 0.59) and increasing high-density lipoprotein level (WMD: 0.02 mmol/l, 95% CI: -0.06 to 0.10). Improved blood pressure (WMD: -1.05 mmHg, 95% CI: -4.29 to 2.19) and triglycerides level (WMD: -0.71 mmol/l, 95% CI: -1.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06 kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patient's needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease.
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http://dx.doi.org/10.1038/s41598-019-41854-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441028PMC
March 2019

A Novel Multiplex PCR-RFLP Method for Simultaneous Genotyping of and .

Malays J Med Sci 2018 Jul 30;25(4):72-81. Epub 2018 Aug 30.

School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia.

Background: Cytochrome P450 3A enzymes exhibit a variety of physiological roles and have been reported to be the most predominant enzymes involved in drugs metabolism. Single nucleotide polymorphisms (SNPs) in the genes that code for these enzymes may result in functional changes that affect enzyme activity. is an important enzyme in the metabolism of many important drugs used in the treatment of breast cancer.

Methods: A total of 94 post-menopausal breast cancer patients were recruited for the study and their DNA was isolated for polymerase chain reaction (PCR). The primers were designed using Primer3 software with primer specificities checked via the Basic Local Alignment Tool (BLAST) database. The primer specificity, functionality and annealing temperature were first investigated using uniplex PCR protocols, followed by a single multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The digested amplification fragments were analysed by gel electrophoresis and subsequently validated by sequencing.

Results: A multiplex PCR-RFLP method was successfully developed for simultaneous detection of , and in a population of post-menopausal breast cancer patients.

Conclusion: The technique is simple, cost-effective, time-saving and can be routinely applied in the identification of SNPs and determination of allelic and genotypic frequencies of , and .
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http://dx.doi.org/10.21315/mjms2018.25.4.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422546PMC
July 2018