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Fulltext Potency of Selected Berries, Grapes, and Citrus Fruit as Neuroprotective Agents

Tan SJ, Ismail IS

Evid Based Complement Alternat Med, 2020;2020:3582947.
PMID: 32565853 DOI: 10.1155/2020/3582947

A healthy diet should nourish the brain with essential nutrients, including bioactive compounds, for normal brain functioning and to protect it from the negative effects of inflammation and oxidative stress. In this review, a concise summation of the protective effects of selected fruits, namely, berries, grapes, and citrus fruits, against neurological disorder is presented. The focus is on the neuroprotective potential of these fruits against neurodegenerative and mental disorders. The fruits selection was based on the vast reported pharmacological studies on their neuroprotection efficacies. Hence, the respective knowledge and limitations are discussed based on the biological and pharmacological evidence compiled from the previously reported laboratory, epidemiology, and intervention trials.
Unusual nitrogenous derivatives from Alstonia

Tan SJ, Subramaniam G, Thomas NF, Kam TS

Nat Prod Commun, 2012 Jun;7(6):739-42.
PMID: 22816296

Five new nitrogenous compounds were isolated from the Malayan Alstonia angustifolia and their structures determined based on interpretation of spectroscopic data.
Macroline-sarpagine and macroline-pleiocarpamine bisindole alkaloids from Alstonia angustifolia

Tan SJ, Lim KH, Subramaniam G, Kam TS

Phytochemistry, 2013 Jan;85:194-202.
PMID: 22995929 DOI: 10.1016/j.phytochem.2012.08.016

Nine bisindole alkaloids, comprising four belonging to the macroline-sarpagine group, and five belonging to the macroline-pleiocarpamine group, were isolated from the stem-bark extracts of Alstonia angustifolia (Apocynacea). Their structures were established using NMR and MS analyses.
Lumutinines A-D, linearly fused macroline-macroline and macroline-sarpagine bisindoles from Alstonia macrophylla

Lim SH, Tan SJ, Low YY, Kam TS

J Nat Prod, 2011 Dec 27;74(12):2556-62.
PMID: 22148233 DOI: 10.1021/np200730j

Four new linearly fused bisindole alkaloids, lumutinines A-D (1-4), were isolated from the stem-bark extract of Alstonia macrophylla. Lumutinines A (1) and B (2) represent the first examples of linear, ring A/F-fused macroline-macroline-type bisindoles, while lumutinines C (3) and D (4) were constituted from the union of macroline and sarpagine moieties. A reinvestigation of the stereochemical assignment of alstoumerine (8) by NMR and X-ray diffraction analyses indicated that the configuration at C-16 and C-19 required revision.
Bipleiophylline, an unprecedented cytotoxic bisindole alkaloid constituted from the bridging of two indole moieties by an aromatic spacer unit

Kam TS, Tan SJ, Ng SW, Komiyama K

Org. Lett., 2008 Sep 4;10(17):3749-52.
PMID: 18683934 DOI: 10.1021/ol801354s

A cytotoxic bisindole alkaloid possessing an unprecedented structure in which two indole moieties are bridged by an aromatic spacer unit has been isolated from Alstonia angustifolia. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway from pyrocatechuic acid and pleiocarpamine is presented.
Fulltext Statistical Optimization of Flavonoid and Antioxidant Recovery from Macerated Chinese and Malaysian Lotus Root (Nelumbo nucifera) Using Response Surface Methodology

Tan SJ, Lee CK, Gan CY, Olalere OA

Molecules, 2021 Apr 01;26(7).
PMID: 33916148 DOI: 10.3390/molecules26072014

In this study, the combination of parameters required for optimal extraction of anti-oxidative components from the Chinese lotus (CLR) and Malaysian lotus (MLR) roots were carefully investigated. Box-Behnken design was employed to optimize the pH (X1: 2-3), extraction time (X2: 0.5-1.5 h) and solvent-to-sample ratio (X3: 20-40 mL/g) to obtain a high flavonoid yield with high % DPPHsc free radical scavenging and Ferric-reducing power assay (FRAP). The analysis of variance clearly showed the significant contribution of quadratic model for all responses. The optimal conditions for both Chinese lotus (CLR) and Malaysian lotus (MLR) roots were obtained as: CLR: X1 = 2.5; X2 = 0.5 h; X3 = 40 mL/g; MLR: X1 = 2.4; X2 = 0.5 h; X3 = 40 mL/g. These optimum conditions gave (a) Total flavonoid content (TFC) of 0.599 mg PCE/g sample and 0.549 mg PCE/g sample, respectively; (b) % DPPHsc of 48.36% and 29.11%, respectively; (c) FRAP value of 2.07 mM FeSO4 and 1.89 mM FeSO4, respectively. A close agreement between predicted and experimental values was found. The result obtained succinctly revealed that the Chinese lotus exhibited higher antioxidant and total flavonoid content when compared with the Malaysia lotus root at optimum extraction condition.
DOES GLYCEMIC CONTROL HAVE A DOSE-RESPONSE RELATIONSHIP WITH IMPLANT OUTCOMES? A COMPREHENSIVE SYSTEMATIC REVIEW AND META-ANALYSIS

Tan SJ, Baharin B, Nabil S, Mohd N, Zhu Y

J Evid Based Dent Pract, 2021 Jun;21(2):101543.
PMID: 34391557 DOI: 10.1016/j.jebdp.2021.101543

OBJECTIVES: To comprehensively evaluate implant survival, clinical and biochemical parameters, as well as possible dose-response relationship with hemoglobin A1c (HbA1c) in patients with differing diabetic control.
METHODOLOGY: Five electronic databases were searched for studies that compared implant outcomes in patients with differing HbA1c values. Research quality was evaluated using Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Narrative synthesis and meta-analysis were performed for survival rate, plaque index (PI), bleeding on probing (BOP), probing pocket depth, and marginal bone loss (MBL). Categorical dose-response meta-analysis (DRMA) was conducted according to length of follow-up.
RESULTS: Twenty-two studies met the inclusion criteria. Prospective studies were mostly of moderate quality, but non-prospective papers had serious to critical risk of bias. Survival rate was high for the first 3 years (92.6%-100%) for patients with HbA1c less than 8%. Meta-analysis revealed worsening clinical parameters with increasing HbA1c. DRMA further established a significant dose-response relationship between glycemic control with BOP (10% more bleeding, 95% CI 0.05-0.16, P = .008) and MBL (0.05 mm more bone loss, 95% CI 0.01-0.09, P = .002) per HbA1c category, but no association with probing pocket depth. Osseointegration progressed at a slower rate, and inflammatory cytokines and bone biomarkers were adversely affected in patients with HbA1c above 8%.
CONCLUSION: Moderate evidence suggests a high short-term survival but possible dose-response trend of worsening BOP and MBL in association with glycemic control. Clinically, HbA1c values must be considered for risk assessment before placement and throughout the lifespan of the implant placed in a patient with diabetes.
Fulltext Effect of Anti-Diabetic Medications on Dental Implants: A Scoping Review of Animal Studies and Their Relevance to Humans

Tan SJ, Baharin B, Mohd N, Nabil S

Pharmaceuticals (Basel), 2022 Dec 05;15(12).
PMID: 36558969 DOI: 10.3390/ph15121518

Animal studies have ascertained that hyperglycemia adversely affects bone metabolism and dental implant osseointegration. However, diabetic patients show low occurrence of unfavorable hard or soft peri-implant tissue changes, differences that are possibly due to treatment with anti-diabetic medications. This scoping review aimed to systematically examine the effects of these drugs on implant outcomes and explore the predictive modality of animal studies for clinical practice according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Three electronic databases (MEDLINE, EBSCOHost, and Cochrane) were searched according to the PRISMA-ScR standards for studies on diabetic animals that received titanium implants and anti-diabetic treatments. Risk assessment was performed using the SYRCLE Risk-of-Bias (RoB) tool. Twenty-one papers were included, encompassing six types of medications. Fifteen studies were on T1DM animals, and only six involved T2DM models. T1DM animals were treated with non-insulin drugs in four investigations, while insulin was utilized in 11 other studies. In T2DM experiments, five administered non-insulin drugs, and only one applied locally delivered insulin. Only insulin in T1DM studies produced a positive influence on bone-implant contact (BIC), bone mineral content, and removal torque values. Inappropriate drug selection, inadequate glycemic control, and high RoB depict a mismatch between the research focus and the translational rationale to clinical practice. There remains a knowledge gap regarding T2DM investigations due to the lack of studies. More data are needed concerning intraoral implants and the performance of osseointegrated implants in patients with a later onset of diabetes. Future research should reflect the pathophysiology and treatment of each type of diabetes to ensure clinical applicability.
Oxidized derivatives of macroline, sarpagine, and pleiocarpamine alkaloids from Alstonia angustifolia

Tan SJ, Lim JL, Low YY, Sim KS, Lim SH, Kam TS

J Nat Prod, 2014 Sep 26;77(9):2068-80.
PMID: 25211145 DOI: 10.1021/np500439u

A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.
Perhentidines A-C: macroline-macroline bisindoles from Alstonia and the absolute configuration of perhentinine and macralstonine

Lim SH, Low YY, Tan SJ, Lim KH, Thomas NF, Kam TS

J Nat Prod, 2012 May 25;75(5):942-50.
PMID: 22559995 DOI: 10.1021/np300120p

Three new bisindole alkaloids of the macroline-macroline type, perhentidines A-C (1-3), were isolated from the stem-bark extract of Alstonia macrophylla and Alstonia angustifolia. The structures of these alkaloids were established on the basis of NMR and MS analyses. The absolute configurations of perhentinine (4) and macralstonine (5) were established by X-ray diffraction analyses, which facilitated assignment of the configuration at C-20 in the regioisomeric bisindole alkaloids perhentidines A-C (1-3). A potentially useful method for the determination of the configuration at C-20 based on comparison of the NMR chemical shifts of the bisindoles and their acetate derivatives, in these and related bisindoles with similar constitution and branching of the monomeric units, is also presented.
Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba

Ku WF, Tan SJ, Low YY, Komiyama K, Kam TS

Phytochemistry, 2011 Dec;72(17):2212-8.
PMID: 21889176 DOI: 10.1016/j.phytochem.2011.08.001

A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.
Strychnan and secoangustilobine A type alkaloids from Alstonia spatulata. Revision of the C-20 configuration of scholaricine

Tan SJ, Low YY, Choo YM, Abdullah Z, Etoh T, Hayashi M, et al.

J Nat Prod, 2010 Nov 29;73(11):1891-7.
PMID: 21043460 DOI: 10.1021/np100552b

A total of 25 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia spatulata, of which five are new alkaloids of the strychnan type (alstolucines A-E, 1-5) and the other, a new alkaloid of the secoangustilobine A type (alstolobine A, 6). The structures of these alkaloids were established using NMR and MS analysis and, in the case of alstolucine B (2), also confirmed by X-ray diffraction analysis. A reinvestigation of the stereochemical assignment of scholaricine (13) by NMR and X-ray analyses indicated that the configuration at C-20 required revision. Alkaloids 1, 2, 6, 7, 9, 10, and 13 reversed multidrug resistance in vincristine-resistant KB cells.
Fulltext All-Optical Modulation Technology Based on 2D Layered Materials

Yang H, Wang Y, Tiu ZC, Tan SJ, Yuan L, Zhang H

Micromachines (Basel), 2022 Jan 07;13(1).
PMID: 35056256 DOI: 10.3390/mi13010092

In the advancement of photonics technologies, all-optical systems are highly demanded in ultrafast photonics, signal processing, optical sensing and optical communication systems. All-optical devices are the core elements to realize the next generation of photonics integration system and optical interconnection. Thus, the exploration of new optoelectronics materials that exhibit different optical properties is a highlighted research direction. The emerging two-dimensional (2D) materials such as graphene, black phosphorus (BP), transition metal dichalcogenides (TMDs) and MXene have proved great potential in the evolution of photonics technologies. The optical properties of 2D materials comprising the energy bandgap, third-order nonlinearity, nonlinear absorption and thermo-optics coefficient can be tailored for different optical applications. Over the past decade, the explorations of 2D materials in photonics applications have extended to all-optical modulators, all-optical switches, an all-optical wavelength converter, covering the visible, near-infrared and Terahertz wavelength range. Herein, we review different types of 2D materials, their fabrication processes and optical properties. In addition, we also summarize the recent advances of all-optical modulation based on 2D materials. Finally, we conclude on the perspectives on and challenges of the future development of the 2D material-based all-optical devices.
Nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics studies on non-organic soybeans versus organic soybeans (Glycine max), and their fermentation by Rhizopus oligosporus

Chong SG, Ismail IS, Ahmad Azam A, Tan SJ, Shaari K, Tan JK

J Sci Food Agric, 2023 Apr;103(6):3146-3156.
PMID: 36426592 DOI: 10.1002/jsfa.12355

BACKGROUND: Soybeans (Glycine max) are high in proteins and isoflavones, which offer many health benefits. It has been suggested that the fermentation process enhances the nutrients in the soybeans. Organic foods are perceived as better than non-organic foods in terms of health benefits, yet little is known about the difference in the phytochemical content that distinguishes the quality of organic soybeans from non-organic soybeans. This study investigated the chemical profiles of non-organic (G, T, U, UB) and organic (C, COF, A, R, B, Z) soybeans (G. max [L.] Merr.) and their metabolite changes after fermentation with Rhizopus oligosporus.
RESULTS: A clear separation was only observed between non-organic G and organic Z, which were then selected for further investigation in the fermentation of soybeans (GF and ZF). All four groups (G, Z, GF, ZF) were analyzed using nuclear magnetic resonance (NMR) spectroscopy along with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this way a total of 41 and 47 metabolites were identified respectively, with 12 in common. A clear variation (|log1.5 FC| > 2 and P
Fulltext Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units

Ho SF, Tan SJ, Mazlan MZ, Iberahim S, Lee YX, Hassan R

Diagnostics (Basel), 2023 Jul 21;13(14).
PMID: 37510189 DOI: 10.3390/diagnostics13142445

Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.
Fulltext Comparing the cost, glycaemic control and medication adherence of utilizing patients' own medicines (POMs) versus usual dispensing among diabetic patients in an outpatient setting

Lim PC, Chung YY, Tan SJ, Wong TY, Permalu DD, Cheah TK, et al.

Daru, 2021 Jun;29(1):125-132.
PMID: 33538999 DOI: 10.1007/s40199-021-00389-6

BACKGROUND: Millions worth of unused drugs particularly those indicated for chronic diseases such as diabetes were returned and disposed leading to substantial wastage. Use of patients' own medications (POMs) in the inpatient setting has reduced wastage and saved cost. The impact of utilizing POMs in the outpatient setting has hitherto not been determined.
PURPOSE: This study aims to compare the cost, medication adherence and glycaemic control of utilizing POMs versus usual dispensing.
METHODS: Prospective randomized controlled study was conducted among diabetic patients that required monthly medication refill in the Outpatient Pharmacy in 2017. Patients who consented were equally divided into POMs and control groups. Both groups brought excess medications from home at week-0 and week-12. Patients in the POMs group brought excess medications monthly and sufficient amount of drugs were added until the next refill date. Drugs were dispensed as usual in the control group. Total cost consisting of the cost of drugs, staff and building was calculated. Glycosylated haemoglobin (HbA1c) was measured at baseline and week-12. Adherence was measured based on pill counting.
RESULTS: Thirty patients aged 56.77 ± 14.67 years with 13.37 ± 7.36 years of diabetes participated. Baseline characteristics were similar between the groups. POMs minimized the total cost by 38.96% which translated to a cost saving of USD 42.76 ± 6.98, significantly different versus USD 0.02 ± 0.52 in the control group, p = 0.025. Mean HbA1c reduced significantly (-0.79%, p = 0.016) in the POMs group but not significant in the control group (-0.11%, p = 0.740). Medication adherence improved significantly in both groups at week-12 (p

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