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  1. Direct recovery of cyclodextringlycosyltransferase from Bacillus cereus using aqueous two-phase flotation
    Lin YK, Show PL, Yap YJ, Tan CP, Ng EP, Ariff AB, et al.
    J Biosci Bioeng, 2015 Dec;120(6):684-9.
    PMID: 26111602 DOI: 10.1016/j.jbiosc.2015.04.013
    Purification of cyclodextrin glycosyl transferase (CGTase) from Bacillus cereus using polyethylene glycol (PEG)-potassium phosphates aqueous two-phase flotation (ATPF) system was studied in this paper. The effects of varying PEG molecular weight, tie-line length (TLL) value, volume ratio (VR), pH value, crude concentration and gas nitrogen flotation time were investigated. The optimal condition for purification of CGTase was attained at 18.0% (w/w) PEG 8000, 7.0% (w/w) potassium phosphates, VR of 3.0, 20% (w/w) crude load at pH 7, and 80 min nitrogen flotation time at a flow rate of 5 L/min. With this optimal condition, purification factor (PFT) of 21.8 and a yield (YT) of 97.1% were attained. CGTase was successfully purified in a single downstream processing step using the ATPF.
  2. Medicinal Mushrooms and Their Use to Strengthen Respiratory Health during and Post-COVID-19 Pandemic
    Booi HN, Lee MK, Fung SY, Ng ST, Tan CS, Lim KH, et al.
    Int J Med Mushrooms, 2022;24(10):1-14.
    PMID: 36374826 DOI: 10.1615/IntJMedMushrooms.2022045068
    COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.
  3. Fulltext A comparison study of dental pulp stem cells derived from healthy and orthodontically intruded human permanent teeth for mesenchymal stem cell characterisation
    Lau MN, Kunasekaran W, On YY, Tan LJ, Zaharin NA, H A Ghani S, et al.
    PLoS One, 2022;17(12):e0279129.
    PMID: 36574419 DOI: 10.1371/journal.pone.0279129
    The objective of this study was to compare the characteristics of Dental Pulp Stem Cells (DPSCs) derived from healthy human permanent teeth with those that were orthodontically-intruded to serve as potential Mesenchymal Stem Cells (MSC). Recruited subjects were treated with orthodontic intrusion on one side of the maxillary first premolar while the opposite side served as the control for a period of six weeks before the dental pulp was extracted. Isolated DPSCs from both the control and intruded samples were analyzed, looking at the morphology, growth kinetics, cell surface marker profile, and multilineage differentiation for MSC characterisation. Our study showed that cells isolated from both groups were able to attach to the cell culture flask, exhibited fibroblast-like morphology under light microscopy, able to differentiate into osteogenic, adipogenic and chondrogenic lineages as well as tested positive for MSCs cell surface markers CD90 and CD105 but negative for haematopoietic cell surface markers CD34 and HLA-DR. Both groups displayed a trend of gradually increasing population doubling time from passage 1 to passage 5. Viable DPSCs from both groups were successfully recovered from their cryopreserved state. In conclusion, DPSCs in the dental pulp of upper premolar not only remained viable after 6 weeks of orthodontic intrusion using fixed appliances but also able to develop into MSCs.
  4. Simple and high sample throughput LC/ESI-MS/MS method for bioequivalence study of prazosin, a drug with risk of orthostatic hypotension
    Loh GOK, Wong EYL, Tan YTF, Wee HC, Ng RS, Syed HK, et al.
    Drug Dev Ind Pharm, 2022 Sep;48(9):470-479.
    PMID: 36111737 DOI: 10.1080/03639045.2022.2125985
    OBJECTIVE: The study aimed to develop a rapid, simple and sensitive LC/ESI-MS/MS method to measure prazosin concentration in human plasma and apply bedside sampling in bioequivalence study of two prazosin tablets to resolve the adverse effect of orthostatic hypotension.

    SIGNIFICANCE: The LC/ESI-MS/MS prazosin method was highly sensitive and selective. Bedside sampling reduced the orthostatic hypotension incidence and subject dropout rate.

    METHODS: After sample preparation, prazosin and terazosin (IS) were detected on mass spectrometer operating in multiple reaction monitoring mode using positive ionization. Mobile phase flow rate was set at 0.40 mL/min with sample run time of 1.75 min. The bioanalytical method was validated as per EMEA and FDA guidelines. Bedside sampling was performed in bioequivalence study for the first 4 h after dosing. The three primary pharmacokinetic parameters, Cmax, AUC0-t and AUC0-∞ and 90% confidence interval were determined.

    RESULTS: The small injection volume of 1 μL minimized instrumentation contamination and prolonged the analytical column lifespan. Linearity was obtained between 0.5 and 30.0 ng/mL, with coefficient of determination, r2 ≥ 0.99. The mean extraction recovery of prazosin and IS was >92%, with precision value (CV, %) ≤ 10.3%. Only two orthostatic hypotension adverse events were reported. The two prazosin formulations were found to be bioequivalent.

    CONCLUSION: The LC/ESI-MS/MS method has shown robustness and reliability exemplified by the incurred sample re-analysis result. Bedside sampling should be proposed for bioequivalence or pharmacokinetic studies of drugs demonstrating adverse event of orthostatic hypotension.

  5. Fulltext Community phylogeny and spatial scale affect phylogenetic diversity metrics in a species-rich rainforest in Borneo
    Okuno S, Yin T, Nanami S, Matsuyama S, Kamiya K, Tan S, et al.
    Ecol Evol, 2022 Nov;12(11):e9536.
    PMID: 36440315 DOI: 10.1002/ece3.9536
    Community phylogenetic analysis is an effective approach to understanding the process of community formation. The phylogenetic tree of the species pool is reconstructed in the first step, and the phylogenetic tree obtained in the second step is used to analyze phylogenetic diversity. Sythetic trees have often been used in the construction of phylogenentic trees; however, in tropical rainforests with many closely related species, synthetic trees contain many unresolved nodes, which may affect the results of phylogenetic structure analysis. Here, we constructed a phylogenetic tree using DNA barcode sequences (rbcL, matK, trnH-psbA) for 737 tree species from the rainforests of Borneo, which have a high-species diversity and many closely related species. The phylogenetic tree had fewer polytomies and more branch length variations than the Phylocom synthetic trees. Comparison of community phylogenetic analyses indicated that values of the standardized effect size of mean pairwise distance (SES-MPD) were highly correlated between Phylocom and DNA barcode trees, but less so for the standardized effect size of mean nearest taxon distance (SES-MNTD), suggesting that caution is needed when using synthetic trees for communities containing many congeneric species, especially when using SES-MNTD. Simulation analysis suggested that spatial dependence on phylogenetic diversity is related to the phylogenetic signal of the species' habitat niche and the spatial structure of habitat, indicating the importance of detailed phylogeny in understanding community assembly processes.
  6. Evaluation of quality and protein structure of natural water kefir-fermented quinoa protein concentrates
    Alrosan M, Tan TC, Easa AM, Gammoh S, Alu'datt MH, Aleid GM, et al.
    Food Chem, 2023 Mar 15;404(Pt B):134614.
    PMID: 36444092 DOI: 10.1016/j.foodchem.2022.134614
    The utilisation of quinoa protein concentrates (QPCs) is limited due to their poor protein digestibility (78.54 %). In this study, QPCs (1 % w/v) were fermented in 5 % (v/v) water kefir grains (WKG) for 5 days at 25 °C. The protein quality of the fermented QPCs was enhanced, whereby the protein digestibility increased significantly (P 
  7. Megacities' environmental assessment for Iraq region using satellite image and geo-spatial tools
    Tao H, Hashim BM, Heddam S, Goliatt L, Tan ML, Sa'adi Z, et al.
    Environ Sci Pollut Res Int, 2023 Mar;30(11):30984-31034.
    PMID: 36441299 DOI: 10.1007/s11356-022-24153-8
    Urban areas are quickly established, and the overwhelming population pressure is triggering heat stress in the metropolitan cities. Climate change impact is the key aspect for maintaining the urban areas and building proper urban planning because spreading of the urban area destroyed the vegetated land and increased heat variation. Remote sensing-based on Landsat images are used for investigating the vegetation circumstances, thermal variation, urban expansion, and surface urban heat island or SUHI in the three megacities of Iraq like Baghdad, Erbil, and Basrah. Four satellite imageries are used aimed at land use and land cover (LULC) study from 1990 to 2020, which indicate the land transformation of those three major cities in Iraq. The average annually temperature is increased during  30 years like Baghdad (0.16 °C), Basrah (0.44 °C), and Erbil (0.32 °C). The built-up area is increased 147.1 km2 (Erbil), 217.86 km2 (Baghdad), and 294.43 km2 (Erbil), which indicated the SUHI affects the entire area of the three cities. The bare land is increased in Baghdad city, which indicated the local climatic condition and affected the livelihood. Basrah City is affected by anthropogenic activities and most areas of Basrah were converted into built-up land in the last 30 years. In Erbil, agricultural land (295.81 km2) is increased. The SUHI study results indicated the climate change effect in those three cities in Iraq. This study's results are more useful for planning, management, and sustainable development of urban areas.
  8. Fulltext Changes in genital Human Papillomavirus (HPV) prevalence among urban females a decade after the Malaysian HPV vaccination program
    Khoo SP, Muhammad Ridzuan Tan NA, Rajasuriar R, Nasir NH, Gravitt P, Ng CW, et al.
    PLoS One, 2022;17(12):e0278477.
    PMID: 36538522 DOI: 10.1371/journal.pone.0278477
    To increase the coverage of HPV vaccination, Malaysia implemented a national school-based vaccination program for all 13-year-old girls in 2010. Two years later, a clinic-based catch-up program was started for 16 to 21-year-old girls. We assessed the prevalence of a range of HPV genotypes, among a sample of urban women within the age groups of 18-24 and 35-45 years in 2019-2020, a decade into the national vaccination program. The HPV prevalence was then compared to that reported in an unvaccinated population in 2013-2015. We sampled a total of 1134 participants, comprising of 277 women aged 18-24 years and 857 women aged 35-45 years, from several urban clinics in the state of Selangor. Participants provided a self-acquired vaginal sample for HPV genotyping. Comprehensive sociodemographic and vaccination history were collected. The HPV vaccination coverage among women in the younger age group increased from 9.3% in 2013-2015 to 75.5% in 2019-2020. The prevalence of vaccine-targeted HPV16/18 decreased 91% (CI: 14.5%-99.0%) among the younger women, from 4.0% in 2013-2015 to 0.4% in 2019-2020. There was also an 87% (CI: 27.5%-97.5%) reduction in HPV6/11/16/18. There was no difference in the prevalence of non-vaccine targeted HPV genotypes among younger women. The HPV prevalence among older women, for both vaccine targeted and non-vaccine targeted genotypes in 2019-2020, did not differ from 2013-2015. The observed decline in prevalence of vaccine-targeted HPV genotype among younger women a decade after the national HPV vaccination program is an early indication of its effectiveness in reducing the burden of cervical cancer.
  9. Insights into chitosan-based cellulose nanowhiskers reinforced nanocomposite material via deep eutectic solvent in green chemistry
    Chang XX, Mubarak NM, Karri RR, Tan YH, Khalid M, Dehghani MH, et al.
    Environ Res, 2023 Feb 15;219:115089.
    PMID: 36529332 DOI: 10.1016/j.envres.2022.115089
    In the present work, the synthesis of cellulose nanowhiskers (CNW)/chitosan nanocomposite films via deep eutectic solvents (DES) changing the chemical structures were carried out. It was observed that a pure chitosan film has broadband at 3180-3400 cm-1, indicating amide and hydroxyl groups. Upon CNW incorporation, the peak gets sharper and stronger and shifts to a greater wavelength. Further, the addition of DES infuses more elements of amide into the nanocomposite films. Moreover, the mechanical properties incorporating CNW filler into a chitosan matrix show an enhancement in tensile strength (TS), Young's modulus (YM), and elongation at break. The TS and YM increase while the elongation decrease as the CNW concentration increases. The YM of biocomposite films is increased to 723 MPa at 25% CNW into chitosan films. Besides, the TS has enhanced to 11.48 MPa at 15% CNW concentration in the biocomposite films. The elongation at break has decreased to 11.7% at 25% CNW concentration. Hence, incorporating CNW into the chitosan matrix via DES can still improve the mechanical properties of the nanocomposite films. Therefore, the application of DES results in a lower YM and TS as the films are hygroscopic. In conclusion, DES can be considered the new green solvent media for synthesizing materials. It has the potential to replace ionic liquids due to its biodegradability and non-toxic properties while preserving the character of low-vapour pressure. Besides that, chitosan can be used as potential material for applications in process industries, such as the biomedical and pharmaceutical industries. Thus, DES can be used as a green solvent and aim to reduce the toxic effect of chemicals on the environment during chemical production.
  10. Fulltext Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections
    Najafi S, Tan SC, Aghamiri S, Raee P, Ebrahimi Z, Jahromi ZK, et al.
    Biomed Pharmacother, 2022 Apr;148:112743.
    PMID: 35228065 DOI: 10.1016/j.biopha.2022.112743
    Viral infections are a common cause of morbidity worldwide. The emergence of Coronavirus Disease 2019 (COVID-19) has led to more attention to viral infections and finding novel therapeutics. The CRISPR-Cas9 system has been recently proposed as a potential therapeutic tool for the treatment of viral diseases. Here, we review the research progress in the use of CRISPR-Cas technology for treating viral infections, as well as the strategies for improving the delivery of this gene-editing tool in vivo. Key challenges that hinder the widespread clinical application of CRISPR-Cas9 technology are also discussed, and several possible directions for future research are proposed.
  11. Fulltext Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action
    Lai JW, Maah MJ, Tan KW, Sarip R, Lim YAL, Ganguly R, et al.
    Malar J, 2022 Dec 17;21(1):386.
    PMID: 36528584 DOI: 10.1186/s12936-022-04406-0
    BACKGROUND: Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed.

    METHODS: The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains.

    RESULTS: Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis.

    CONCLUSION: The dinuclear [Cu(phen)-4,4'-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.

  12. Prevalence of seizures in brain tumor: A meta-analysis
    Audrey C, Lim KS, Ahmad Zaki R, Fong SL, Chan CY, Sathis Kumar T, et al.
    Epilepsy Res, 2022 Nov;187:107033.
    PMID: 36274423 DOI: 10.1016/j.eplepsyres.2022.107033
    OBJECTIVES: Prevalence of seizures in brain tumors vary substantially between studies even with similar histopathological types. We aimed to identify the seizure prevalence of the commonest types of brain tumors.

    METHODS: Systematic computerized search of PubMed, Embase, and Web of Science were performed. The meta-analysis of pooled prevalence and 95 % confidence interval (CI) for tumor-related seizures were calculated by using a random effect model. Based on the 2014 epilepsy definition, a mean seizure prevalence of 60 % is used to indicate high seizure prevalence in this study.

    RESULTS: 74 studies that reported seizure prevalence with 23,116 patients were included in this meta-analysis. These tumors has higher seizure incidence rate (at least 60 %) with pooled prevalence of 63 % for adult with low-grade astrocytoma (95 % CI: 57-68 %), 65 % for oligodendroglioma (95% CI: 57-72 %), 72 % for oligoastrocytoma (95 % CI: 67-77 %), 81 % for ganglioglioma (95 % CI: 66-97 %) and 94 % for DNET (94 % CI: 83-100 %).

    CONCLUSION: This study highlights the type of brain tumors that carry a high seizure prevalence. Screening for subtle seizures and early management of seizures may be beneficial in patients with low-grade astrocytoma (adult), oligodendroglioma, oligoastrocytoma, ganglioglioma or DNET brain tumor.

  13. Fulltext Sustainable fall prevention across Europe: challenges and opportunities
    van der Velde N, Seppala L, Petrovic M, Ryg J, Tan MP, Montero-Odasso M, et al.
    Aging Clin Exp Res, 2022 Oct;34(10):2553-2556.
    PMID: 35829992 DOI: 10.1007/s40520-022-02178-w
  14. Fulltext Hypertension care in demographic surveillance sites: a cross-sectional study in Bangladesh, India, Indonesia, Malaysia, Viet Nam
    Geldsetzer P, Tan MM, Dewi FS, Quyen BT, Juvekar S, Hanifi SM, et al.
    Bull World Health Organ, 2022 Oct 01;100(10):601-609.
    PMID: 36188011 DOI: 10.2471/BLT.22.287807
    Objective: To determine the proportion of adults with hypertension who reported: (i) having been previously diagnosed with hypertension; (ii) taking blood pressure-lowering medication; and (iii) having achieved hypertension control, in five health and demographic surveillance system sites across five countries in Asia.

    Methods: Data were collected during household surveys conducted between 2016 and 2020 in the five surveillance sites in Bangladesh, India, Indonesia, Malaysia and Viet Nam. We defined hypertension as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or taking blood pressure-lowering medication. We defined hypertension control as systolic blood pressure

  15. Insecticidal activities of Streptomyces sp. KSF103 ethyl acetate extract against medically important mosquitoes and non-target organisms
    Amelia-Yap ZH, Low VL, Saeung A, Ng FL, Chen CD, Hassandarvish P, et al.
    Sci Rep, 2023 Jan 02;13(1):4.
    PMID: 36593229 DOI: 10.1038/s41598-022-25387-9
    A potentially novel actinobacterium isolated from forest soil, Streptomyces sp. KSF103 was evaluated for its insecticidal effect against several mosquito species namely Aedes aegypti, Aedes albopictus, Anopheles cracens and Culex quinquefasciatus. Mosquito larvae and adults were exposed to various concentrations of the ethyl acetate (EA) extract for 24 h. Considerable mortality was evident after the EA extract treatment for all four important vector mosquitoes. Larvicidal activity of the EA extract resulted in LC50 at 0.045 mg/mL and LC90 at 0.080 mg/mL for Ae. aegypti; LC50 at 0.060 mg/mL and LC90 at 0.247 mg/mL for Ae. albopictus; LC50 at 2.141 mg/mL and LC90 at 6.345 mg/mL for An. cracens; and LC50 at 0.272 mg/mL and LC90 at 0.980 mg/mL for Cx. quinquefasciatus. In adulticidal tests, the EA extract was the most toxic to Ae. albopictus adults (LD50 = 2.445 mg/mL; LD90 = 20.004 mg/mL), followed by An. cracens (LD50 = 5.121 mg/mL; LD90 = 147.854 mg/mL) and then Ae. aegypti (LD50 = 28.873 mg/mL; LD90 = 274.823 mg/mL). Additionally, the EA extract exhibited ovicidal activity against Ae. aegypti (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), Ae. albopictus (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), and An. cracens (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), evaluated up to 168 h post-treatment. It displayed no toxicity on the freshwater microalga Chlorella sp. Beijerinck UMACC 313, marine microalga Chlorella sp. Beijerinck UMACC 258 and the ant Odontoponera denticulata. In conclusion, the EA extract showed promising larvicidal, adulticidal and ovicidal activity against Ae. aegypti, Ae. albopictus, An. cracens, and Cx. quinquefasciatus (larvae only). The results suggest that the EA extract of Streptomyces sp. KSF103 has the potential to be used as an environmental-friendly approach in mosquito control. The current study would serve as an initial step toward complementing microbe-based bioinsecticides for synthetic insecticides against medically important mosquitoes.
  16. In vivo anti-tumor activity of Lignosus rhinocerus TM02® using a MCF7-xenograft NCr nude mice model
    Ng MJ, Kong BH, Teoh KH, Yap YH, Ng ST, Tan CS, et al.
    J Ethnopharmacol, 2023 Mar 25;304:115957.
    PMID: 36509254 DOI: 10.1016/j.jep.2022.115957
    ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerus (Cooke) Ryvarden (also known as Tiger Milk mushroom, TMM), is a basidiomycete belonging to the Polyporaceae family. It has been documented to be used by traditional Chinese physicians and indigenous people in Southeast Asia to treat a variety of illnesses, such as gastritis, arthritis, and respiratory conditions, as well as to restore patients' physical well-being. TMM has also been used in folk medicine to treat cancer. For example, people from the indigenous Kensiu tribe of northeast Kedah (Malaysia) apply shredded TMM sclerotium mixed with water directly onto breast skin to treat breast cancer, while Chinese practitioners from Hong Kong, China prescribe TMM sclerotium as a treatment for liver cancer. L. rhinocerus has previously been demonstrated to possess selective anti-proliferative properties in vitro, however pre-clinical in vivo research has not yet been conducted.

    AIM OF STUDY: This study aimed to examine the anti-tumor activities of L. rhinocerus TM02®, using two different sample preparations [cold water extract (CWE) and fraction] via various routes of administration (oral and intraperitoneal) on an MCF7-xenograft nude mouse model. This study also investigated the inhibitory effect of TM02® CWE and its fractions against COX-2 in vitro using LPS-induced RAW264.7 macrophages, on the basis of the relationship between COX-2 and metastasis, apoptosis resistance, as well as the proliferation of cancer cells.

    MATERIALS AND METHODS: The first preparation, L. rhinocerus TM02® sclerotium powder (TSP) was dissolved in cold water to obtain the cold water extract (CWE). It was further fractionated based on its molecular weight to obtain the high (HMW), medium (MMW) and low (LMW) molecular weight fractions. The second preparation, known as the TM02® rhinoprolycan fraction (TRF), was obtained by combining the HMW and MMW fractions. TSP was given orally to mimic the daily consumption of a supplement; TRF was administered intraperitoneally to mimic typical tumorous cancer treatment with a rapid and more thorough absorption through the peritoneal cavity. Another experiment was conducted to examine changes in COX-2 activity in LPS-induced RAW264.7 macrophages after a 1-h pre-treatment with CWE, HMW, and MMW.

    RESULTS: Our results revealed that intraperitoneal TRF-injection (90 μg/g BW) for 20 days reduced initial tumor volume by ∼64.3% (n = 5). The percentage of apoptotic cells was marginally higher in TRF-treated mice vs. control, suggesting that induction of apoptosis as one of the factors that led to tumor shrinkage. TSP (500 μg/g BW) oral treatment (n = 5) for 63 days (inclusive of pre-treatment prior to tumor inoculation) effectively inhibited tumor growth. Four of the five tumors totally regressed, demonstrating the effectiveness of TSP ingestion in suppressing tumor growth. Although no significant changes were found in mouse serum cytokines (TNF-α, IL-5, IL-6 and CCL2), some increasing and decreasing trends were observed. This may suggest the immunomodulatory potential of these treatments that can directly or indirectly affect tumor growth. Pre-treatment with CWE, HMW and MMW significantly reduced COX-2 activity in RAW264.7 macrophages upon 24 h LPS-stimulation, suggesting the potential of L. rhinocerus TM02® extract and fractions in regulating M1/M2 polarization.

    CONCLUSION: Based on the findings of our investigation, both the rhinoprolycan fraction and crude sclerotial powder from L. rhinocerus TM02® demonstrated tumor suppressive effects, indicating that they contain substances with strong anticancer potential. The antitumor effects of L. rhinocerus TM02® in our study highlights the potential for further explorations into its mechanism of action and future development as a prophylactic or adjunct therapeutic against tumorous cancer.

  17. KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia
    Kevin-Tey WF, Wen WX, Bee PC, Eng HS, Ho KW, Tan SM, et al.
    Hum Immunol, 2023 Mar;84(3):172-185.
    PMID: 36517321 DOI: 10.1016/j.humimm.2022.11.006
    Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation-maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.
  18. Fulltext Lysine-specific demethylase 1 deficiency modifies aldosterone synthesis in a sex-specific manner
    Tan YJD, Brooks DL, Wong KYH, Huang Y, Romero JR, Williams JS, et al.
    J Endocrinol, 2023 Jan 01;256(1).
    PMID: 36327153 DOI: 10.1530/JOE-22-0141
    Biologic sex influences the development of cardiovascular disease and modifies aldosterone (ALDO) and blood pressure (BP) phenotypes: females secrete more ALDO, and their adrenal glomerulosa cell is more sensitive to stimulation. Lysine-specific demethylase 1 (LSD1) variants in Africans and LSD1 deficiency in mice are associated with BP and/or ALDO phenotypes. This study, in 18- and 40-week-old wild type (WT) and LSD1+/- mice, was designed to determine whether (1) sex modifies ALDO biosynthetic enzymes; (2) LSD1 deficiency disrupts the effect of sex on these enzymes; (3) within each genotype, there is a positive relationship between ALDO biosynthesis (proximate phenotype), plasma ALDO (intermediate phenotype) and BP levels (distant phenotype); and (4) sex and LSD1 genotype interact on these phenotypes. In WT mice, female sex increases the expression of early enzymes in ALDO biosynthesis but not ALDO levels or systolic blood pressure (SBP). However, enzyme expressions are shifted downward in LSD1+/- females vs males, so that early enzyme levels are similar but the late enzymes are substantially lower. In both age groups, LSD1 deficiency modifies the adrenal enzyme expressions, circulating ALDO levels, and SBP in a sex-specific manner. Finally, significant sex/LSD1 genotype interactions modulate the three phenotypes in mice. In conclusion, biologic sex in mice interacts with LSD1 deficiency to modify several phenotypes: (1) proximal (ALDO biosynthetic enzymes); (2) intermediate (circulating ALDO); and (3) distant (SBP). These results provide entry to better understand the roles of biological sex and LSD1 in (1) hypertension heterogeneity and (2) providing more personalized treatment.
  19. Fulltext Response: Safety and adverse events following COVID-19 vaccination among people with epilepsy: Correspondence
    Ong MJY, Khoo CS, Lee YX, Poongkuntran V, Tang CK, Choong YJ, et al.
    Epilepsia Open, 2023 Mar;8(1):236.
    PMID: 36504315 DOI: 10.1002/epi4.12675
  20. Fulltext Effects of the COVID-19 Pandemic on Psychological Status and Quality of Life among Participants of the Malaysian Elders Longitudinal Research (MELoR) Study
    Aravindhan K, Morgan K, Mat S, Hamid TA, Ibrahim R, Saedon NI, et al.
    Ann Geriatr Med Res, 2022 Dec;26(4):354-362.
    PMID: 36503184 DOI: 10.4235/agmr.22.0134
    BACKGROUND: This study aimed to identify differences in quality of life before and during the coronavirus disease 2019 (COVID-19) pandemic and determine the influence of psychological status on the observed changes in the quality of life among older adults.

    METHODS: The Malaysian Elders Longitudinal Research study recruited Malaysians aged at least 55 years from 2013 to 2015. Follow-ups were conducted between September and December 2020. Quality of life was determined using the 12-item Control, Autonomy, Self-Realization, and Pleasure questionnaire. Psychological statuses were assessed using the 21-item Depression Anxiety and Stress Scale, 15-item Geriatric Depression Scale, and 4-item Perceived Stress Scale.

    RESULTS: This study included data from 706 individuals (mean age, 73.3±6.8 years). We observed reduced quality of life and increased anxiety among 402 (43.1%) and 144 (20.9%) participants, respectively. Participants felt "out of control," "left out," "short of money," and "life was full of opportunities" less often and could "please themselves with what they did" more often. Multivariate analyses revealed increased depression, anxiety, and stress as independent risk factors for reduced quality of life.

    CONCLUSION: Individuals with increased depression, anxiety, and stress levels during the pandemic experienced a worsening quality of life. Thus, the development of effective strategies to address the mental health of older adults is needed to mitigate the effects of the pandemic on their quality of life.

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