Browse publications by year: 2018

  1. Chan DD, Chang LY, Akesson KE, Mitchell P, Chen CH, Lewiecki EM, et al.
    Arch Osteoporos, 2018 05 12;13(1):59.
    PMID: 29754189 DOI: 10.1007/s11657-018-0463-3
    The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region.

    PURPOSE: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region.

    METHODS: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version.

    RESULTS: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased.

    CONCLUSIONS: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

    MeSH terms: Asia/epidemiology; Congresses as Topic; Delivery of Health Care/standards*; Humans; Societies, Medical*; Consensus*; Australasia/epidemiology; Secondary Prevention/standards*; Osteoporotic Fractures/epidemiology; Osteoporotic Fractures/prevention & control*
  2. Cheah FK, Leong KH, Thomas NF, Chin HK, Ariffin A, Awang K
    Apoptosis, 2018 Jun;23(5-6):329-342.
    PMID: 29754265 DOI: 10.1007/s10495-018-1457-8
    Resveratrol, a naturally occurring polyphenolic antioxidant, is a potential chemoprophylactic agent for various cancers, including colorectal cancer. Although emerging evidence continually suggests that a number of resveratrol derivatives may be better cancer chemopreventive candidates than resveratrol, studies on the mechanism of action of these derivatives are limited. This is the first study which investigates the mechanism underlying the cytotoxic effect of a synthesized resveratrol analogue, (E)-N-(2-(4-methoxystyryl) phenyl) furan-2-carboxamide (CS) on colorectal cancer. Previously, our group reported a series of synthesized resveratrol analogues, which showed cytotoxicity against a panel of cancer cell lines, in particular on colon cancer cells. In this study, we further discovered that CS also exerts a potent suppressive effect on HCT116 colorectal cancer cells. In contrast, normal colon cells (CCD-112 Con) were not sensitive to CS up to 72 h post treatment. CS caused cytotoxicity in HCT116 cells through several apoptotic events including activation of the Fas death receptor, FADD, caspase 8, caspase 3, caspase 9, and cleaved PARP, which occurred alongside cell cycle arrest from the up-regulation of p53 and p21. The results show that CS causes apoptosis via the activation of an extrinsic pathway leading to caspase activation and cell cycle arrest from activated p53. These findings suggest that CS may be a potential candidate for development as an anti-tumor agent in the future.
  3. Abu-Alnaeem MF, Yusoff I, Ng TF, Alias Y, Raksmey M
    Sci Total Environ, 2018 Feb 15;615:972-989.
    PMID: 29751448 DOI: 10.1016/j.scitotenv.2017.09.320
    A comprehensive study was conducted to identify the salinization origins and the major hydrogeochemical processes controlling the salinization and deterioration of the Gaza coastal aquifer system through a combination approaches of statistical and geostatistical techniques, and detailed hydrogeochemical assessments. These analyses were applied on ten physicochemical variables for 219 wells using STATA/SE12 and Surfer softwares. Geostatistical analysis of the groundwater salinity showed that seawater intrusion along the coastline, and saltwater up-coning inland highly influenced the groundwater salinity of the study area. The hierarchical cluster analysis (HCA) technique yielded seven distinct hydrogeochemical signature clusters; (C1&C2: Eocene brackish water invasion, C3 saltwater up-coning, C4 human inputs, C5 seawater intrusion, C6 & C7 rainfall and mixing inputs). Box plot shows a wide variation of most of the ions while Chadha's plot elucidates the predominance of Na-Cl (71.6%) and Ca/Mg-Cl (25%) water types. It is found that, the highest and the lowest levels of salinization and the highest level of nitrate pollution were recorded in the northern area. This result reflects the sensitivity of this area to the human activities and/or natural actions. Around 90.4% of the wells are nitrate polluted. The main source of nitrate pollution is the sewage inputs while the farming inputs are very limited and restricted mostly in the sensitive northern area. Among the hydrogeochemical processes, ion exchange process was the most effective process all over the study area. Carbonate dissolution was common in the study area with the highest level in clusters 6, 7, 4 and 2 in the north while Gypsum dissolution was significant only in cluster 1 in the south and limited in the other clusters. This integrated multi-techniques research should be of benefit for effective utilization and management of the Gaza coastal aquifer system as well as for future work in other similar aquifers systems.
    MeSH terms: Environmental Monitoring*; Middle East; Water Pollutants, Chemical/analysis; Water Supply/statistics & numerical data*; Salinity*; Groundwater/chemistry*; Water Wells
  4. Chamoso P, González-Briones A, Rivas A, Bueno De Mata F, Corchado JM
    Sensors (Basel), 2018 May 03;18(5).
    PMID: 29751554 DOI: 10.3390/s18051416
    Rapid advances in technology make it necessary to prepare our society in every aspect. Some of the most significant technological developments of the last decade are the UAVs (Unnamed Aerial Vehicles) or drones. UAVs provide a wide range of new possibilities and have become a tool that we now use on a daily basis. However, if their use is not controlled, it could entail several risks, which make it necessary to legislate and monitor UAV flights to ensure, inter alia, the security and privacy of all citizens. As a result of this problem, several laws have been passed which seek to regulate their use; however, no proposals have been made with regards to the control of airspace from a technological point of view. This is exactly what we propose in this article: a platform with different modes designed to control UAVs and monitor their status. The features of the proposed platform provide multiple advantages that make the use of UAVs more secure, such as prohibiting UAVs’ access to restricted areas or avoiding collisions between vehicles. The platform has been successfully tested in Salamanca, Spain.
    MeSH terms: Industrial Development; Risk; Societies; Spain; Technology; Privacy
  5. Jolly JJ, Chin KY, Alias E, Chua KH, Soelaiman IN
    PMID: 29751644 DOI: 10.3390/ijerph15050963
    Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells), osteoclasts (bone resorbing cells), and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.
    MeSH terms: Aged; Bone and Bones/drug effects*; Bone Resorption; Humans; Phytotherapy*; Osteoblasts/drug effects; Osteoclasts/drug effects; Osteoporosis/drug therapy*; Plants, Medicinal*
  6. Azri FA, Sukor R, Selamat J, Abu Bakar F, Yusof NA, Hajian R
    Toxins (Basel), 2018 May 11;10(5).
    PMID: 29751668 DOI: 10.3390/toxins10050196
    Mycotoxins are the secondary toxic metabolites produced naturally by fungi. Analysis of mycotoxins is essential to minimize the consumption of contaminated food and feed. In this present work, an ultrasensitive electrochemical immunosensor for the detection of aflatoxin B₁ (AFB₁) was successfully developed based on an indirect competitive enzyme-linked immunosorbent assay (ELISA). Various parameters of ELISA, including antigen⁻antibody concentration, blocking agents, incubation time, temperature and pH of reagents, were first optimized in a 96-well microtiter plate to study the antigen⁻antibody interaction and optimize the optimum parameters of the assay. The optimized assay was transferred onto the multi-walled carbon nanotubes/chitosan/screen-printed carbon electrode (MWCNTs/CS/SPCE) by covalent attachment with the aid of 1-Ethyl-3-(3-dimetylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Competition occurred between aflatoxin B₁-bovine serum albumin (AFB₁⁻BSA) and free AFB₁ (in peanut sample and standard) for the binding site of a fixed amount of anti-AFB₁ antibody. Differential pulse voltammetry (DPV) analysis was used for the detection based on the reduction peak of TMB(ox). The developed immunosensor showed a linear range of 0.0001 to 10 ng/mL with detection limit of 0.3 pg/mL. AFB₁ analysis in spiked peanut samples resulted in recoveries between 80% and 127%. The precision of the developed immunosensor was evaluated by RSD values (n = 5) as 4.78% and 2.71% for reproducibility and repeatability, respectively.
    MeSH terms: Animals; Antibodies/immunology; Caseins/chemistry; Enzyme-Linked Immunosorbent Assay; Food Contamination/analysis; Milk/chemistry; Arachis/chemistry; Protein Binding; Serum Albumin, Bovine/chemistry; Biosensing Techniques*; Aflatoxin B1/analysis*; Aflatoxin B1/immunology; Aflatoxin B1/chemistry; Electrochemical Techniques
  7. Siriviriyanun A, Tsai YJ, Voon SH, Kiew SF, Imae T, Kiew LV, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Aug 01;89:307-315.
    PMID: 29752102 DOI: 10.1016/j.msec.2018.04.020
    In this study, nanohybrid materials consisting of graphene oxide (GO), β‑cyclodextrin (CD) and poly(amido amine) dendrimer (DEN) were successfully prepared by covalent bonding. GO-CD and GO-CD-DEN were found to be potential nanocarriers for anticancer drugs including chemotherapeutics (doxorubicin (DOX), camptothecin (CPT)) and photosensitizer (protoporphyrin IX (PpIX)). GO-CD possessed 1.2 times higher DOX-loading capacity than GO due to inclusion of additional DOX to the CD. The drug loading on GO-CD-DEN increased in the order: DOX 
    MeSH terms: Antineoplastic Agents/metabolism; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry*; Camptothecin/metabolism; Camptothecin/pharmacology; Camptothecin/chemistry; Cell Survival/drug effects; Cyclodextrins/chemistry*; Doxorubicin/metabolism; Doxorubicin/pharmacology; Doxorubicin/chemistry; Drug Carriers/chemistry*; Graphite/chemistry*; Humans; Light; Oxides/chemistry; Protoporphyrins/metabolism; Protoporphyrins/pharmacology; Protoporphyrins/chemistry; Photosensitizing Agents/metabolism; Photosensitizing Agents/pharmacology; Photosensitizing Agents/chemistry*; Microscopy, Atomic Force; Cell Line, Tumor; Dendrimers/chemistry*; Drug Liberation
  8. Sun H, Chen G, Sunarso J, Dai J, Zhou W, Shao Z
    ACS Appl Mater Interfaces, 2018 May 23;10(20):16939-16942.
    PMID: 29741862 DOI: 10.1021/acsami.8b03702
    An abundant, highly active, and durable oxygen evolution reaction (OER) electrocatalyst is an enabling component for a more sustainable energy future. We report, herein, a molybdenum and niobium codoped B-site-ordered double perovskite oxide with a compositional formula of Ba2CoMo0.5Nb0.5O6-δ (BCMN) as an active and robust catalyst for OER in an alkaline electrolyte. BCMN displayed a low overpotential of 445 mA at a current density of 10 mA cm-2disk. BCMN also showed long-term stability in an alkaline medium. This work hints toward the possibility of combining a codoping approach with double perovskite structure formation to achieve significant enhancement in the OER performance.
  9. Abu-Serie MM, Habashy NH, Attia WE
    BMC Complement Altern Med, 2018 May 10;18(1):154.
    PMID: 29747629 DOI: 10.1186/s12906-018-2218-5
    BACKGROUND: Since oxidative stress and inflammation are two linked factors in the pathogenesis of several human diseases. Thus identification of effective treatment is of great importance. Edible mushroom and microalgae are rich in the effective antioxidant phytochemicals. Hence, their beneficial effects on oxidative stress-associated inflammation are extremely required to be investigated.

    METHODS: This study evaluated the functional constituents, antioxidant and anti-inflammatory activities of Malaysian Ganoderma lucidum aqueous extract (GLE) and Egyptian Chlorella vulgaris ethanolic extract (CVE). Also, the synergistic, addictive or antagonistic activities of the combination between the two extracts (GLE-CVE) were studied. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-kappa B, as well as levels of nitric oxide, tumor necrosis factor (TNF)-α, lipid peroxidation, reduced glutathione and antioxidant enzymes were determined using in vitro model of lipopolysaccharide-stimulated white blood cells.

    MeSH terms: Anti-Inflammatory Agents/pharmacology*; Anti-Inflammatory Agents/chemistry; Antioxidants/pharmacology*; Antioxidants/chemistry; Cell Survival/drug effects; Cells, Cultured; Drug Synergism; Humans; Leukocytes; Lipopolysaccharides/toxicity; Plant Extracts/pharmacology; Plant Extracts/chemistry; Oxidative Stress/drug effects*; Ganoderma/chemistry*; Chlorella vulgaris/chemistry*; Phytochemicals/pharmacology*; Phytochemicals/chemistry
  10. Ab Malik N, Abdul Razak F, Mohamad Yatim S, Lam OLT, Jin L, Li LSW, et al.
    J Evid Based Dent Pract, 2018 06;18(2):99-109.
    PMID: 29747810 DOI: 10.1016/j.jebdp.2017.08.002
    OBJECTIVE: To evaluate the presence of oral opportunistic pathogens among stroke survivors, both before and after oral health care interventions.

    METHODS: A multicenter randomized clinical trial was conducted on hospitalized stroke survivors. Those in the control group were given standard care of oral hygiene (a manual toothbrush and toothpaste), whereas those in the test group were given intense care of oral hygiene (a powered toothbrush and 1% chlorhexidine oral gel). Oral clinical assessments were carried out, and microbiological samples were collected, using concentrated oral rinse samples at 3 time points: baseline, 3 months, and 6 months.

    RESULTS: The prevalence of oral yeast was significantly reduced in the test group at 6 months (P < .05), but no significant difference was observed over time. A significant reduction was observed in the prevalence of Staphylococcus aureus (P < .01) and aerobic and facultative gram-negative bacilli over time (P < .05), but there were no significant differences noted between groups at 6 months. Candida albicans and Klebsiella pneumoniae were the prominent pathogens determined throughout the trial. Kluyvera strains have also been isolated from this cohort.

    CONCLUSION: Oral hygiene intervention using a powered tooth brush and 1% chlorhexidine oral gel was effective in reducing the prevalence of oral opportunistic pathogens.

    MeSH terms: Chlorhexidine*; Humans; Oral Health; Toothbrushing; Prevalence; Survivors; Stroke*
  11. Leung AKC, Leong KF, Lam JM
    J Pediatr, 2018 Sep;200:285-285.e1.
    PMID: 29747932 DOI: 10.1016/j.jpeds.2018.04.012
  12. Ahmad H, Umar K, Ali SG, Singh P, Islam SS, Khan HM
    Mikrochim Acta, 2018 05 10;185(6):290.
    PMID: 29748777 DOI: 10.1007/s00604-018-2829-z
    A column sorbent for arsenic was obtained through immobilization of highly branched polyethylenimine (PEI) on graphene oxide (GO). The composite material enables speciation of arsenic by tuning the pH of the sample solution which governs the surface charge of the sorbent, depending on whether amino groups (-NH2) are present (at high pH) or ammonium groups (-NH3+; at low pH). The composite can be applied to improved speciation of arsenic (compared to unmodified GO). There is no need for oxidation or reduction of arsenic. A column procedure was applied for the sequestered extraction and speciation of As(III) and As(V) from environmental water samples before their determination by hydride generation-microwave induced plasma-atomic emission spectrometry. The method has a preconcentration factor of 440 for As(III) and of 400 for As(V). The limits of detection (at 3 S/N) are extremely low, being 1.8 ± 0.2 ngL-1 for As(III) and 1.3 ± 0.08 ngL-1 for As(V). This is much lower than the arsenic guideline value of 10 μgL-1 as given by the WHO. Graphical abstract Graphene oxide interconnected with polyethyleneimine has been employed for the speciation and determination of arsenic. Quantitation by atomic emission spectroscopy reveals a high preconcentration factor (440 and 400) and low LODs of 1.8 ± 0.2 and 1.3 ± 0.08 ngL-1for As(III) and As(V), respectively.
  13. Ling LS, Sidi H, Lope RAR, Das S, Baharudin A
    Curr Drug Targets, 2018 May 11.
    PMID: 29749310 DOI: 10.2174/1389450119666180511161420
    Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively. Cross sex hormone, i.e. FMTO, or MFTO has biological and psychological influences on the transgender individuals. Nevertheless, cross sex hormone may also poses a range of side effect profiles, varies from the biological to psychosocial impact. The psychological impact can be paramount until it causes severe mental-health problems and even suicide. Numerous ranges of bio-psycho-social influence of cross-sex hormone were highlighted in this review as fundamental core knowledge in the art to know practice when dealing with the treatment options. In psychiatry, the change in the biological appearance may have great influence in the transgender individual, especially in the context of psychosocial and cultural perspective.
    MeSH terms: Androgen Antagonists; Cognition; Estrogens; Female; Gender Identity; Humans; Male; Psychiatry; Gonadal Steroid Hormones; Suicide; Testosterone; Transsexualism; Transgender Persons
  14. Bashiru G, Bahaman AR
    Indian J Med Res, 2018 Jan;147(1):15-22.
    PMID: 29749356 DOI: 10.4103/ijmr.IJMR_1022_16
    Considerable progress has been made in the field of leptospiral vaccines development since its first use as a killed vaccine in guinea pigs. Despite the fact that the immunity conferred is restricted to serovars with closely related lipopolysaccharide antigen, certain vaccines have remained useful, especially in endemic regions, for the protection of high-risk individuals. Other conventional vaccines such as the live-attenuated vaccine and lipopolysaccharide (LPS) vaccine have not gained popularity due to the reactive response that follows their administration and the lack of understanding of the pathogenesis of leptospirosis. With the recent breakthrough and availability of complete genome sequences of Leptospira, development of novel vaccine including recombinant protein vaccine using reverse vaccinology approaches has yielded encouraging results. However, factors hindering the development of effective leptospiral vaccines include variation in serovar distribution from region to region, establishment of renal carrier status following vaccination and determination of the dose and endpoint titres acceptable as definitive indicators of protective immunity. In this review, advancements and progress made in LPS-based vaccines, killed- and live-attenuated vaccines, recombinant peptide vaccines and DNA vaccines against leptospirosis are highlighted.
    MeSH terms: Animals; Guinea Pigs; Leptospira; Leptospirosis; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated; Vaccines, DNA; Vaccines, Subunit; Serogroup
  15. Moi IM, Leow ATC, Ali MSM, Rahman RNZRA, Salleh AB, Sabri S
    Appl Microbiol Biotechnol, 2018 Jul;102(14):5811-5826.
    PMID: 29749565 DOI: 10.1007/s00253-018-9063-9
    Polyunsaturated fatty acids (PUFAs) play an important role in human diet. Despite the wide-ranging importance and benefits from heart health to brain functions, humans and mammals cannot synthesize PUFAs de novo. The primary sources of PUFA are fish and plants. Due to the increasing concerns associated with food security as well as issues of environmental contaminants in fish oil, there has been considerable interest in the production of polyunsaturated fatty acids from alternative resources which are more sustainable, safer, and economical. For instance, marine bacteria, particularly the genus of Shewanella, Photobacterium, Colwellia, Moritella, Psychromonas, Vibrio, and Alteromonas, are found to be one among the major microbial producers of polyunsaturated fatty acids. Recent developments in the area with a focus on the production of polyunsaturated fatty acids from marine bacteria as well as the metabolic engineering strategies for the improvement of PUFA production are discussed.
    MeSH terms: Bacteria/metabolism*; Bacteria/chemistry; Fatty Acids, Unsaturated/biosynthesis*; Bioengineering; Aquatic Organisms/metabolism*; Aquatic Organisms/chemistry
  16. Jolly JJ, Chin KY, Farhana MFN, Alias E, Chua KH, Hasan WNW, et al.
    Iran J Med Sci, 2018 Mar;43(2):208-213.
    PMID: 29749990
    Osteoblasts (OBs) and osteoclasts (OCs) are 2 major groups of bone cells. Their cell-to-cell interactions are important to ensure the continuity of the bone-remodeling process. Therefore, the present study was carried out to optimize an OB/OC co-culture system utilizing the human OB cell line hFOB 1.19 and OCs extracted from peripheral blood mononuclear cells (PBMNCs). It was a 2-step procedure, involving the optimization of the OB culture and the co-culture of the OBs with PBMNCs at an optimum ratio. Firstly, pre-OBs were cultured to 90% confluency and the time required for differentiation was determined. OB differentiation was determined using the van Gieson staining to detect the presence of collagen and Alizarin Red for calcium. Secondly, OBs and OCs were co-cultured at the ratios of 1 OC: 1 OB, 1 OC: 4 OBs, 2 OCs: 1 OB, and 1 OC: 2 OBs. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the differentiation of the OCs. The results showed that collagen was present on day 1, whereas calcium was detected as early as day 3. Based on the result of TRAP staining, 1 OC: 2 OBs was taken as the most appropriate ratio. No macrophage colony-stimulating factor and receptor activator of the nuclear factor-κB ligand were added because they were provided by the OBs. In conclusion, these optimization processes are vital as they ensure the exact time point and ratio of the OB/OC co-culture in order to produce a reliable and reproducible co-culture system.
    MeSH terms: Anthraquinones; Cell Communication; Cell Differentiation; Cell Line; Collagen; Humans; Leukocytes, Mononuclear; Osteoblasts; Osteoclasts; Staining and Labeling; Tartrates; Macrophage Colony-Stimulating Factor; NF-kappa B; Coculture Techniques
  17. Subramaniam M, Liew SK, In L, Awang K, Ahmed N, Nagoor NH
    Drug Des Devel Ther, 2018;12:1053-1063.
    PMID: 29750018 DOI: 10.2147/DDDT.S141925
    Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects.

    Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression.

    Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation.

    Conclusion: Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

    MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry; Antineoplastic Combined Chemotherapy Protocols/pharmacology*; Antineoplastic Combined Chemotherapy Protocols/chemistry; Benzyl Alcohols/pharmacology*; Benzyl Alcohols/chemistry; Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Survival/drug effects; Cells, Cultured; Cisplatin/pharmacology*; Cisplatin/chemistry; Diffusion; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Microbial Sensitivity Tests; Mycobacterium/drug effects*; Structure-Activity Relationship; NF-kappa B/antagonists & inhibitors*; NF-kappa B/metabolism; Cell Death/drug effects; Cell Proliferation/drug effects
  18. Chai BK, Lau YS, Loong BJ, Rais MM, Ting KN, Dharmani DM, et al.
    Physiol Res, 2018 Nov 14;67(5):729-740.
    PMID: 29750886
    The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.
    MeSH terms: Adrenergic beta-Agonists/pharmacology; Animals; Blood Glucose/drug effects; Blood Glucose/metabolism; Body Weight/drug effects; Body Weight/physiology; Isoproterenol/pharmacology*; Male; Vasodilation/drug effects; Vasodilation/physiology*; Rats, Sprague-Dawley; Linoleic Acids, Conjugated/administration & dosage; Linoleic Acids, Conjugated/adverse effects*; Atherosclerosis/blood*; Atherosclerosis/chemically induced; Atherosclerosis/etiology; Rats; Diet, High-Fat/adverse effects*
  19. Cunningham AB, Brinckmann JA, Pei SJ, Luo P, Schippmann U, Long X, et al.
    J Ethnopharmacol, 2018 Sep 15;223:142-151.
    PMID: 29751123 DOI: 10.1016/j.jep.2018.05.004
    ETHNOPHARMACOLOGICAL RELEVANCE: Fritillaria cirrhosa D. Don bulbs contain alkaloids and are one of the most intensively exploited alpine Himalayan medicinal species. In terms of proprietary medicines, our study shows that 210 F. cirrhosa products are offered by 46 suppliers, most of which (44) are situated in China and two in Nepal. A widespread commercial use is as one of the main ingredients in cough syrups. A well known example is "Nin Jiom Pei Pa Koa Herbal Cough & Throat Syrup", which typically contains more F. cirrhosa than any other herbal ingredient in the formulation. The biggest market for F. cirrhosa bulbs is China, where demand exceeds supply of this wild harvested species for use in traditional Chinese medicine (TCM). Cross-border trade from Nepal to China occurs in significant quantities. Bhutan also imports F. cirrhosa bulbs from Nepal. In addition, F. cirrhosa is registered as an active ingredient in traditional herbal medicinal preparations in Australia, Canada, Hong Kong SAR, Malaysia, Republic of Korea, Singapore and Taiwan. There is also an export trade in F. cirrhosa to Europe. Assessing how much F. cirrhosa is traded is complex, however, due to a "look-alike" challenge, as nine Chinese Fritillaria species are traded in Europe (Fritillaria cirrhosa, F. delavayi, F. hupehensis, F. pallidiflora, F. przewalskii, F. thunbergii, F. unibracteata, F. ussuriensis and F. walujewii).

    AIMS OF THE STUDY: The aims of this review were to assess the scale of the global trade in F. cirrhosa, and to synthesise studies of the impacts of wild harvest on F. cirrhosa populations and on the extent of emerging cultivation initiatives as an alternative to wild harvest.

    METHODS: Firstly, we reviewed published information on studies on impacts of wild F. cirrhosa harvest from across the geographic range of this species. Secondly, global trade data for F. cirrhosa were analysed.

    RESULTS: The principal demand for F. cirrhosa bulbs is in China, where hundreds of different companies produce Fritillaria preparations. Trade data also show that in 2013, China exported over 44 tonnes of F. cirrhosa bulbs to Taiwan and 26.7 tonnes to the Republic of Korea. Extensive commercial use and limited wild stocks result in a high price (2000 - 3800 CNY per kg (around US$ 303 -560 per kg in 2017)) for F. cirrhosa bulbs. Prices of cultivated Fritillaria bulbs are much lower (600-680 CNY per kg in 2017) than wild harvested bulbs. But due to very specific growth requirements of F. cirrhosa, cultivation is not yet able to meet total demand. The consequence is continued exploitation of wild stocks. At the same time, however, an increasing proportion of the demand is met by cultivation of alternative Fritillaria species that are easier to grow than F. cirrhosa. The air-dry mass of F. cirrhosa bulbs varies between 0.0917 and 0.1116 g per bulb. This represents 8960 - 10,900 bulbs/kg or 8.9 - 10.9 million bulbs per tonne. Current demand therefore represents billions of bulbs per year.

    CONCLUSIONS: Demand for F. cirrhosa bulbs, particularly from China, makes this species one of the most intensively harvested alpine Himalayan medicinal bulbs. Although F. cirrhosa is listed as a Class III protected species in China, billions of these tiny, wild harvested bulbs are sold per year. Due to demand exceeding supply, the price of F. cirrhosa bulbs has increased dramatically. Between 2002 and 2017, for example, the price of wild harvested F. cirrhosa bulbs increased over nine-fold, from the equivalent of US$60 in 2002 to US$560 per kg in 2017. To date, cultivation has been unable to meet the entire market demand for F. cirrhosa bulbs, although other Fritillaria species are successfully cultivated on a larger scale.

    MeSH terms: Alkaloids; Australia; Bhutan; Canada; China; Cough; Europe; Hong Kong; Malaysia; Medicine, Chinese Traditional; Nepal; Pharynx; Singapore; Taiwan; Ethnopharmacology; Plant Preparations; Fritillaria; Republic of Korea
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