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Fulltext Investigation on the antimicrobial activities of gingers (Etlingera coccinea (Blume) S.Sakai & Nagam and Etlingera sessilanthera R.M.Sm.) endemic to Borneo

Daniel-Jambun D, Dwiyanto J, Lim YY, Tan JBL, Muhamad A, Yap SW, et al.

J Appl Microbiol, 2017 Oct;123(4):810-818.
PMID: 28708293 DOI: 10.1111/jam.13536

AIMS: To investigate the antimicrobial properties of Etlingera coccinea and Etlingera sessilanthera and to isolate and identify the antimicrobial compounds.
METHODS AND RESULTS: Extracts were obtained via sequential solvent extraction method using hexane, dichloromethane, ethyl acetate, methanol and water. Antimicrobial activity testing was done using broth microdilution assay against 17 strains of bacteria. The leaf hexane extract of E. coccinea and rhizome hexane extract of E. sessilanthera showed best antimicrobial activities, with minimum inhibitory concentration (MIC) values ranging from 0·016 to 1 mg ml-1 against Gram-positive bacteria. From these active extracts, two antimicrobials were isolated and identified as trans-2-dodecenal and 8(17),12-labdadiene-15,16-dial with MIC values ranging from 4 to 8 μg ml-1 against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus.
CONCLUSION: Etlingera coccinea and E. sessilanthera demonstrated good antimicrobial activities against clinically relevant bacteria strains. The antimicrobial compounds isolated showed low MIC values, hence suggesting their potential use as antimicrobial agents.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify the potent antimicrobials from these gingers. The antimicrobials isolated could potentially be developed further for use in treatment of bacterial infections. Also, this study warrants further research into other Etlingera species in search for more antimicrobial compounds.
A simple and high efficiency purification of His-tagged turnip yellow mosaic virus-like particle (TYMV-VLP) by nickel ion affinity precipitation

Tan FH, Ng JF, Mohamed Alitheen NB, Muhamad A, Yong CY, Lee KW

J Virol Methods, 2023 Sep;319:114771.
PMID: 37437780 DOI: 10.1016/j.jviromet.2023.114771

Virus-like particles (VLPs) is one of the most favourable subjects of study, especially in the field of nanobiotechnology and vaccine development because they possess good immunogenicity and self-adjuvant properties. Conventionally, VLPs can be tagged and purified using affinity chromatography or density gradient ultracentrifugation which is costly and time-consuming. Turnip yellow mosaic virus (TYMV) is a plant virus, where expression of the viral coat protein (TYMVc) in Escherichia coli (E. coli) has been shown to form VLP. In this study, we report a non-chromatographic method for VLP purification using C-terminally His-tagged TYMVc (TYMVcHis6) as a protein model. Firstly, the TYMVcHis6 was cloned and expressed in E. coli. Upon clarification of cell lysate, nickel (II) chloride [NiCl2; 15 µM or equivalent to 0.0000194% (w/v)] was added to precipitate TYMVcHis6. Following centrifugation, the pellet was resuspended in buffer containing 1 mM EDTA to chelate Ni2+, which is then removed via dialysis. A total of 50% of TYMVcHis6 was successfully recovered with purity above 0.90. Later, the purified TYMVcHis6 was analysed with sucrose density ultracentrifugation, dynamic light scattering (DLS), and transmission electron microscopy (TEM) to confirm VLP formation, which is comparable to TYMVcHis6 purified using the standard immobilized metal affinity chromatography (IMAC) column. As the current method omitted the need for IMAC column and beads while significantly reducing the time needed for column washing, nickel affinity precipitation represents a novel method for the purification of VLPs displaying poly-histidine tags (His-tags).
Harnessing bacterial antimicrobial peptides: a comprehensive review on properties, mechanisms, applications, and challenges in combating antimicrobial resistance

Erriah P, Puan SL, Yahaya NM, Kamil WNIWA, Nordin SA, Muhamad A, et al.

J Appl Microbiol, 2024 Nov 18.
PMID: 39558882 DOI: 10.1093/jambio/

Antimicrobial resistance (AMR) is a significant global health concern, due to the persistence of pathogens and the emergence of resistance in bacterial infections. Bacterial-derived antimicrobial peptides (BAMPs) have emerged as a promising strategy to combat these challenges. Known for their diversity and multifaceted nature, BAMPs are notable bioactive agents which exhibit potent antimicrobial activities against various pathogens. This review explores the intricate properties and underlying mechanisms of BAMPs, emphasizing their diverse applications in addressing AMR. Additionally, the review investigates the mechanisms, analyses the challenges in utilizing BAMPs effectively, and examines their potential applications and associated deployment challenges providing comprehensive insights into how BAMPs can be harnessed to combat AMR across different domains.
Fulltext Gastric trichobezoar in an end-stage renal failure and mental health disorder presented with chronic epigastric pain: A case report

Ali AA, Gurung R, Fuad ZM, Moosa M, Ali I, Abdulla A, et al.

Ann Med Surg (Lond), 2020 Oct;58:76-79.
PMID: 32953103 DOI: 10.1016/j.amsu.2020.08.021

Background: Gastric trichobezoar happens when there is an indigestible substance or food found in the gastrointestinal tract. It is a rare presentation which is usually associated with trichotillomania and trichopagia. The presentation may not be specific and is usually related to dyspepsia-like symptoms. In the worst-case scenario, this may cause gastric outlet or intestinal obstruction which eventually requires surgery.
Case presentation: We present a 36-year-old lady with underlying end-stage renal failure (ESRF) and undiagnosed mental health issues who was treated for recurrent episodes of gastritis. Imaging modalities revealed intragastric foreign body ingestion which is consistent with gastric trichobezoar. She eventually underwent laparotomy and gastrotomy to remove the foreign body. Postoperatively, she was referred and followed-up by the psychiatric team.
Conclusion: Gastric trichobezoar has strong associations with psychiatric disorders. With the co-existence of an ESRF, uraemia might contribute to the aetiology of the trichotillomania and trichophagia. Open surgery is the choice of definitive management especially if bezoars are larger. Should the recurrence be remitted, a biopsychosocial modality and regular haemodialysis is the most sustainable approach to ensure the behaviour does not persist.
Alstoscholactine and Alstolaxepine, Monoterpenoid Indole Alkaloids with γ-Lactone-Bridged Cycloheptane and Oxepane Moieties from Alstonia scholaris

Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.

Org. Lett., 2018 12 21;20(24):8014-8018.
PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592

Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics

Zakaria F, Akhtar MT, Wan Ibrahim WN, Abu Bakar N, Muhamad A, Shohaimi S, et al.

Zebrafish, 2021 02;18(1):42-54.
PMID: 33538644 DOI: 10.1089/zeb.2020.1895

Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.
Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach

Zakaria F, Akhtar MT, Wan Norhamidah WI, Noraini AB, Muhamad A, Shohaimi S, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2023 Feb;264:109501.
PMID: 36336330 DOI: 10.1016/j.cbpc.2022.109501

Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.
Preparation and Preliminary Structure-Activity Relationship Studies of Schwarzinicine A Analogs as Vasorelaxant Agents

Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.

J Nat Prod, 2024 Apr 26;87(4):675-691.
PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707

Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
Fulltext A University-Wide Preparedness Effort in the Alert Phase of COVID-19 Incorporating Community Mental Health and Task-Shifting Strategies: Experience from a Bornean Institute of Higher Learning

Mukhsam MH, Jeffree MS, Pang NTP, Syed Abdul Rahim SS, Omar A, Abdullah MS, et al.

Am J Trop Med Hyg, 2020 Sep;103(3):1201-1203.
PMID: 32705977 DOI: 10.4269/ajtmh.20-0458

The COVID-19 pandemic caught the world by surprise, causing millions of confirmed cases and hundreds of thousands of deaths. Hence, the Malaysian government announced a Movement Control Order at the start of the containment phase to flatten the epidemiological curve. Universiti Malaysia Sabah (UMS), a public university in Borneo, was accelerated into alert phase because of high risk of case importation from more than 400 China incoming undergraduates. Measures to mitigate the potential COVID-19 outbreaks in its population were taken by using conventional public health measures with special attention to task-shifting and widespread community mental health interventions. A Preparedness and Response Centre was established to overseer the mitigating measures happening inside the university. Measures taken included empowerment of frontline staff, strengthening of restrictions, strengthening university health center, vigorous contact tracing, widespread health education, maintaining cultural sensitivity, and establishment of early standard operating procedures and university continuity plans. Hence, UMS was able to ensure no importation of cases into its campus during both acute and containment phases at the nationwide level.