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The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review

Pang LW, Hamzah S, Tan SLJ, Mah SH, Yow HY

Neurochem Res, 2023 Dec;48(12):3485-3511.
PMID: 37578655 DOI: 10.1007/s11064-023-04005-8

Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
YouTube as a source of information for parents about silver diamine fluoride

Hussein AS, Norazlan NS, Radzi NSM, Hamzah SH, Gao X

Eur Arch Paediatr Dent, 2024 Nov 07.
PMID: 39509075 DOI: 10.1007/s40368-024-00958-8

PURPOSE: To depict and evaluate the characteristics, engagement, content, and quality of YouTube videos containing information about silver diamine fluoride (SDF).
METHODS: A total of 200 YouTube™ videos were selected and screened, and the video characteristics and engagement indicators were recorded. They were then reviewed for consistency with current professional guidelines on this topic. Two independent reviewers scored the videos using a customized 8-point scoring and 5-point Global Quality Scale (GQS) to assess the content information and the overall quality of each video. These videos were further classified into good, moderate, and poor videos. Kruskal-Wallis, Chi-squared, and Spearman's correlation tests were used for the statistical analysis.
RESULTS: 110 videos met the inclusion criteria. The median total content score was 3 (IQR = 4) and the median GQS score was 2 (IQR = 2). Less than half (n = 49; 45.5%) of the videos were uploaded by healthcare professionals. The video content was classified as good (n = 26; 23.64%), moderate (n = 43; 39.09%), and poor (n = 41; 37.27%). Good-quality videos have a significantly higher information content score than the other groups (P = 0.001). A strong correlation was found between the total content score and GQS score (rho = 0.970, P = 0.001). Longer duration, higher interaction index, and recent upload are associated with higher content and quality scores.
CONCLUSION: A considerable number of videos are available on YouTube about SDF treatment and are attracting public interest. The content and quality of these videos vary widely and are related to several factors.
Parametric study of coagulant recovery from water treatment sludge towards water circular economy

Shawal NBM, Razali NA, Hairom NHH, Yatim NII, Rasit N, Harun MHC, et al.

Water Sci Technol, 2023 Dec;88(12):3142-3150.
PMID: 38154800 DOI: 10.2166/wst.2023.398

This study aims to recover the used coagulants from two water treatment plants via acidification technique. The water treatment sludge (WTS) was acidified with sulfuric acid (H2SO-4) at variable normalities (0.5, 1, 1.5, 2.0 and 2.5 N). The surface morphology and functionalities of both recovered coagulants were analysed using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The performance of recovered coagulants was tested for turbidity removal in surface water treatment at different coagulant dosages and pH. It was found that the optimum normality of H2SO4 for recovered alum was 1.5 N, where 66% turbidity removal was recorded. The recovered PAC treated with 1.0 N H2SO4 indicated high turbidity removal percentage, which was 50.5%. The turbidity removal increased with increasing coagulant dosage. More than 80% turbidity removal was achieved with 40 mg/L dosage of recovered alum and recovered PAC. Maximum removal (85%) was observed with 50 mg/L dosage of recovered alum. For commercial coagulant, the turbidity removal was higher, with a difference of up to 6% in favor of recovered alum. The potential reuse of coagulants can be explored in order to reduce the operating costs and promotes the reduction of WTS disposal.
Novel drug candidates against antibiotic-resistant microorganisms: A review

Lim JS, Chai YY, Ser WX, Haeren AV, Lim YH, Raja T, et al.

Iran J Basic Med Sci, 2024;27(2):134-150.
PMID: 38234674 DOI: 10.22038/IJBMS.2023.71672.15593

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.
The Cutting-edge of CRISPR for Cancer Treatment and its Future Prospects

Liau KM, Ooi AG, Mah CH, Yong P, Kee LS, Loo CZ, et al.

Curr Pharm Biotechnol, 2024;25(12):1500-1522.
PMID: 37921129 DOI: 10.2174/0113892010258617231020062637

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a versatile technology that allows precise modification of genes. One of its most promising applications is in cancer treatment. By targeting and editing specific genes involved in cancer development and progression, CRISPR has the potential to become a powerful tool in the fight against cancer. This review aims to assess the recent progress in CRISPR technology for cancer research and to examine the obstacles and potential strategies to address them. The two most commonly used CRISPR systems for gene editing are CRISPR/Cas9 and CRISPR/Cas12a. CRISPR/Cas9 employs different repairing systems, including homologous recombination (HR) and nonhomologous end joining (NHEJ), to introduce precise modifications to the target genes. However, off-target effects and low editing efficiency are some of the main challenges associated with this technology. To overcome these issues, researchers are exploring new delivery methods and developing CRISPR/Cas systems with improved specificity. Moreover, there are ethical concerns surrounding using CRISPR in gene editing, including the potential for unintended consequences and the creation of genetically modified organisms. It is important to address these issues through rigorous testing and strict regulations. Despite these challenges, the potential benefits of CRISPR in cancer therapy cannot be overlooked. By introducing precise modifications to cancer cells, CRISPR could offer a targeted and effective treatment option for patients with different types of cancer. Further investigation and development of CRISPR technology are necessary to overcome the existing challenges and harness its full potential in cancer therapy.
FDA-approved CAR T-cell Therapy: A Decade of Progress and Challenges

Ong MZ, Kimberly SA, Lee WH, Ling M, Lee M, Tan KW, et al.

Curr Pharm Biotechnol, 2024;25(11):1377-1393.
PMID: 39034731 DOI: 10.2174/0113892010257212231001082741

CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), Abecma® (Idecabtagene vicleucel), Breyanzi® (lisocabtagene maraleucel), and Yescarta® (axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.
Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients

Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.

Ther Drug Monit, 2013 Oct;35(5):624-30.
PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
Fulltext Cost of elective percutaneous coronary intervention in Malaysia: a multicentre cross-sectional costing study

Lee KY, Ong TK, Low EV, Liow SY, Anchah L, Hamzah S, et al.

BMJ Open, 2017 05 28;7(5):e014307.
PMID: 28552843 DOI: 10.1136/bmjopen-2016-014307

OBJECTIVES: Limitations in the quality and access of cost data from low-income and middle-income countries constrain the implementation of economic evaluations. With the increasing prevalence of coronary artery disease in Malaysia, cost information is vital for cardiac service expansion. We aim to calculate the hospitalisation cost of percutaneous coronary intervention (PCI), using a data collection method customised to local setting of limited data availability.

DESIGN: This is a cross-sectional costing study from the perspective of healthcare providers, using top-down approach, from January to June 2014. Cost items under each unit of analysis involved in the provision of PCI service were identified, valuated and calculated to produce unit cost estimates.

SETTING: Five public cardiac centres participated. All the centres provide full-fledged cardiology services. They are also the tertiary referral centres of their respective regions.

PARTICIPANTS: The cost was calculated for elective PCI procedure in each centre. PCI conducted for urgent/emergent indication or for patients with shock and haemodynamic instability were excluded.

PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures of interest were the unit costs at the two units of analysis, namely cardiac ward admission and cardiac catheterisation utilisation, which made up the total hospitalisation cost.

RESULTS: The average hospitalisation cost ranged between RM11 471 (US$3186) and RM14 465 (US$4018). PCI consumables were the dominant cost item at all centres. The centre with daycare establishment recorded the lowest admission cost and total hospitalisation cost.

CONCLUSIONS: Comprehensive results from all centres enable comparison at the levels of cost items, unit of analysis and total costs. This generates important information on cost variations between centres, thus providing valuable guidance for service planning. Alternative procurement practices for PCI consumables may deliver cost reduction. For countries with limited data availability, costing method tailored based on country setting can be used for the purpose of economic evaluations.

REGISTRATION: Malaysian MOH Medical Research and Ethics Committee (ID: NMRR-13-1403-18234 IIR).

Study site: 5 hospitals (unnamed) of which 1 is a university teaching hospital
Fulltext Comparison of the treatment practice and hospitalization cost of percutaneous coronary intervention between a teaching hospital and a general hospital in Malaysia: A cross sectional study

Lee KY, Wan Ahmad WA, Low EV, Liau SY, Anchah L, Hamzah S, et al.

PLoS One, 2017;12(9):e0184410.
PMID: 28873473 DOI: 10.1371/journal.pone.0184410

INTRODUCTION: The increasing disease burden of coronary artery disease (CAD) calls for sustainable cardiac service. Teaching hospitals and general hospitals in Malaysia are main providers of percutaneous coronary intervention (PCI), a common treatment for CAD. Few studies have analyzed the contemporary data on local cardiac facilities. Service expansion and budget allocation require cost evidence from various providers. We aim to compare the patient characteristics, procedural outcomes, and cost profile between a teaching hospital (TH) and a general hospital (GH).
METHODS: This cross-sectional study was conducted from the healthcare providers' perspective from January 1st to June 30th 2014. TH is a university teaching hospital in the capital city, while GH is a state-level general hospital. Both are government-funded cardiac referral centers. Clinical data was extracted from a national cardiac registry. Cost data was collected using mixed method of top-down and bottom-up approaches. Total hospitalization cost per PCI patient was summed up from the costs of ward admission and cardiac catheterization laboratory utilization. Clinical characteristics were compared with chi-square and independent t-test, while hospitalization length and cost were analyzed using Mann-Whitney test.
RESULTS: The mean hospitalization cost was RM 12,117 (USD 3,366) at GH and RM 16,289 (USD 4,525) at TH. The higher cost at TH can be attributed to worse patients' comorbidities and cardiac status. In contrast, GH recorded a lower mean length of stay as more patients had same-day discharge, resulting in 29% reduction in mean cost of admission compared to TH. For both hospitals, PCI consumables accounted for the biggest proportion of total cost.
CONCLUSIONS: The high PCI consumables cost highlighted the importance of cost-effective purchasing mechanism. Findings on the heterogeneity of the patients, treatment practice and hospitalization cost between TH and GH are vital for formulation of cost-saving strategies to ensure sustainable and equitable cardiac service in Malaysia.
Fulltext Identification and in vitro antimicrobial susceptibility of Brucella species isolated from human brucellosis

Hashim R, Ahmad N, Mohamed Zahidi J, Tay BY, Mohd Noor A, Zainal S, et al.

Int J Microbiol, 2014;2014:596245.
PMID: 25120569 DOI: 10.1155/2014/596245

Brucellosis is a world-wide zoonotic disease with a major impact on the public health. Due to the high risk of laboratory acquired infection, limited laboratory investigations were performed on this organism, including detailed identification and susceptibility study. Brucella melitensis is the commonest aetiological agent for human brucellosis in this region. The in vitro susceptibility pattern against selected antimicrobial agents was assessed using E-test. All isolates were noted to be sensitive to all the antimicrobial agents tested except for rifampicin where elevated MIC > 1 μg/mL was noted in 30 out of 41 isolates tested.
Applications of CRISPR in Parasitology

Tee PYE, Chu SYC, Kok CCY, Foo M, Tan CZJ, Foo JB, et al.

Curr Pharm Biotechnol, 2024 Jul 12.
PMID: 39005116 DOI: 10.2174/0113892010316710240626042205

Clustered Regions of Interspersed Palindromic Repeat (CRISPR)-based techniques have been utilized in various research areas, including agriculture, biotechnology, and medicine. With the use of a short sequence guide RNA and CRISPR-associated (Cas) protein, this technique allows for robust, site-specific manipulation of the genome, aiding researchers in making important biomedical discoveries and scientific advancements. In this review, we explored the applications of CRISPR/Cas systems in the field of parasitology for the identification and validation of novel functional genes, diagnosis of parasitic infections, reduction of parasite virulence, and the disruption of disease transmission. We also discussed how CRISPR can be used for the development of therapeutics, vaccines, and drug discovery. Furthermore, the challenges and future perspectives of this technology are also highlighted.
Integration of copperas and calcium hydroxide as a chemical coagulant and coagulant aid for efficient treatment of palm oil mill effluent

Mohamad NA, Hamzah S, Che Harun MH, Ali A, Rasit N, Awang M, et al.

Chemosphere, 2021 Oct;281:130873.
PMID: 34022596 DOI: 10.1016/j.chemosphere.2021.130873

Palm oil mill effluent (POME) is highly polluted wastewater that is to the environment if discharged directly to water source without proper treatment. Thus, a highly efficient treatment with reasonable cost is needed. This study reports the coagulation treatment of POME using integrated copperas and calcium hydroxide. The properties of copperas were determined using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray diffraction (XRD), and X-ray fluorescence (XRF). Coagulation was conducted using jar test experiments for various coagulant formulations and dosages (1000-5000 mg/L), initial pH (4-10), stirring speed (100-300 rpm), and sedimentation time (30-180 min). The characterisation results show that copperas has a compact gel network structure with strong O-H stretching and monoclinic crystal structure. The effectiveness of integrated copperas and calcium hydroxide (Ca(OH)2) with the formulation of 80:20 removed 77.6%, 73.4%, and 57.0% of turbidity, colour, and chemical oxygen demand (COD), respectively. Furthermore, the integration of copperas and Ca(OH)2 produced heavier flocs (ferric hydroxide), which improved gravity settling. The coagulation equilibrium analysis shows that the Langmuir model best described the anaerobic POME sample as the process exhibited monolayer adsorption. The results of this study show that copperas with the aid of Ca(OH)2 demonstrated high potential in the removal of those parameters from POME with acceptable final pH for discharge. The utilisation of this by-product as a coagulant in effluent treatment can unlock the potential of copperas for wider applications, improve its marketability, and reduce gypsum waste generation from the TiO2 industry.

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