Browse publications by year: 2019

  1. Fulltext 4-(2-(1H-Benzo[d]imidazol-2-ylthio)acetamido)-N-(substituted phenyl)benzamides: design, synthesis and biological evaluation
    Tahlan S, Ramasamy K, Lim SM, Shah SAA, Mani V, Narasimhan B
    BMC Chem, 2019 Dec;13(1):12.
    PMID: 31384761 DOI: 10.1186/s13065-019-0533-7
    Background: Dihydrofolate reductase (DHFR) is an important target for antimetabolite class of antimicrobials because it participates in purine synthesis. 2-mercaptobenzimidazole (2MBI) has similar structural features as purine nucleotides. Given that benzimidazole and similar heteroaromatics have been broadly examined for their anticancer potential, so, we hereby report the design, synthesis and biological studies (i.e. antimicrobial and anticancer studies) of 2MBI derivatives.

    Methodology: The antimicrobial activity of synthesized 2MBI derivatives were evaluated against Gram positive and Gram negative bacterial species as well as fungal species by tube dilution technique whereas their anticancer activity was assessed against human colorectal carcinoma cell line (HCT116) by Sulforhodamine B (SRB) assay. They were also structurally characterized by IR, NMR, MS and elemental analyses.

    Results discussion and conclusion: The antimicrobial activity findings revealed that compound N1 (MIC
    bs,st,
    ca
     = 1.27, 2.54, 1.27 µM), N8 (MIC
    ec
    = 1.43 µM), N22 (MIC
    kp,an
    = 2.60 µM), N23 and N25 (MIC
    sa
    = 2.65 µM) exhibited significant antimicrobial effects against tested strains, i.e. Gram-positive, Gram-negative (bacterial) and fungal strains. The anticancer screening results demonstrated that compounds N9, N18 (IC50 = 5.85, 4.53 µM) were the most potent compounds against cancer cell line (HCT116) even more than 5-FU, the standard drug (IC50 = 9.99 µM).

    MeSH terms: Anti-Infective Agents; Antimetabolites; Benzimidazoles; Cell Line; Gram-Negative Bacteria; Humans; Indicator Dilution Techniques; Purine Nucleotides; Rhodamines; Tetrahydrofolate Dehydrogenase; Colorectal Neoplasms; Inhibitory Concentration 50; Early Detection of Cancer
  2. Fulltext Synthesis of lignin based composites of TiO2 for potential application as radical scavengers in sunscreen formulation
    Ibrahim MNM, Iqbal A, Shen CC, Bhawani SA, Adam F
    BMC Chem, 2019 Dec;13(1):17.
    PMID: 31384766 DOI: 10.1186/s13065-019-0537-3
    Titanium dioxide (TiO2) is added in sunscreens due to its ability to absorb ultraviolet (UV) light. However, upon irradiation of UV light, reactive oxygen species particularly hydroxyl radical which can damage human skin will be generated. In this study, lignin/TiO2 composites were employed to quench the hydroxyl radicals generated by the TiO2. The lignin was extracted from oil palm empty fruit bunch (OPEFB) via kraft and soda pulping processes. The kraft lignin composite was labelled as KL/TiO2 whereas the soda lignin composite was labelled as SL/TiO2. The lignins and the composites were characterized by FTIR, UV spectroscopy, 13C NMR, SEM, EDX, and XRD. The relative hydroxyl radical production of composites and TiO2 were compared through photo-oxidation of coumarin to 7-hydroxycoumarin as a test medium. The effect of types and amounts of lignin used were studied. The KL/TiO2 composite showed the least radical production due to higher phenolic hydroxyl content of kraft lignin. The activity of the hydroxyl radicals will be quenched when it abstract hydrogen atoms from the phenolic hydroxyl groups.
    MeSH terms: Beverages; Coumarins; Fruit; Hydrogen; Lignin; Sunscreening Agents; Titanium; Ultraviolet Rays; Umbelliferones; Reactive Oxygen Species; Spectroscopy, Fourier Transform Infrared; Hydroxyl Radical; Carbon-13 Magnetic Resonance Spectroscopy
  3. Fulltext Synthesis, molecular modelling and biological significance of N-(4-(4-bromophenyl) thiazol-2-yl)-2-chloroacetamide derivatives as prospective antimicrobial and antiproliferative agents
    Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
    MeSH terms: Acetamides; Adenocarcinoma; Anti-Infective Agents; Anti-Bacterial Agents; Antineoplastic Agents; Breast Neoplasms; Cell Line; Humans; Magnetic Resonance Spectroscopy; Receptors, Estrogen; Rhodamines; Molecular Structure; Molecular Docking Simulation
  4. Fulltext Design, synthesis and biological profile of heterocyclic benzimidazole analogues as prospective antimicrobial and antiproliferative agents
    Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.
    BMC Chem, 2019 Dec;13(1):50.
    PMID: 31384798 DOI: 10.1186/s13065-019-0567-x
    Background: Nitrogen containing heterocycles are widely used and investigated by pharmaceutical industry, as they are important in discovery and designing of new drug molecules. Drugs with a benzimidazole nucleus possess exclusive structural features and electron-rich atmosphere, which enable them to bind to a number of biologically important targets and result in a wide range of activities. This has served as the basis of the present study whereby new scaffolds with benzimidazole moiety were designed and synthesized.

    Methods: The structures of synthesized compounds were confirmed by physicochemical and spectral means. The synthesized compounds were screened for their antimicrobial and antiproliferative activities by tube dilution and Sulforhodamine B (SRB) assays, respectively.

    Results and conclusion: The in vitro biological screening results revealed that compound Z24 exhibited promising antimicrobial and anticancer activities which are comparable to standards.

    MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents; Atmosphere; Benzimidazoles; Drug Industry; Electrons; Nitrogen; Rhodamines
  5. Fulltext Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
    Abuelizz HA, Iwana NANI, Ahmad R, Anouar EH, Marzouk M, Al-Salahi R
    BMC Chem, 2019 Dec;13(1):52.
    PMID: 31384800 DOI: 10.1186/s13065-019-0560-4
    Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 µM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids have been synthesized and evaluated their α-glucosidase inhibitory activity. Compounds 6h have shown stronger activity than that of acarbose.
    MeSH terms: alpha-Glucosidases; Binding Sites; Diabetes Mellitus; Glucose; Hydrogen Bonding; Hydrolysis; Ligands; Postprandial Period; Inhibitory Concentration 50; Acarbose; Glycoside Hydrolase Inhibitors
  6. Fulltext 4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile
    Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):60.
    PMID: 31384808 DOI: 10.1186/s13065-019-0575-x
    In order to overcome the challenges of microbial resistance as well as to improve the effectiveness and selectivity of chemotherapeutic agents against cancer, a novel series of 4-(4-bromophenyl)-thiazol-2-amine derivatives was synthesized and its molecular structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were further evaluated for their in vitro antimicrobial activity using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. The antimicrobial activity results revealed that compound p2, p3, p4 and p6 exhibited promising antimicrobial activity that are comparable to standard norfloxacin (antibacterial) and fluconazole (antifungal). Anticancer screening results demonstrated that compound p2 was found to be the most active one against cancer cell line when compared to the rest of the compounds and comparable to the standard drug (5-fluorouracil). The molecular docking study demonstrated that compounds, p2, p3, p4 and p6 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and showed promising ADME properties.
    MeSH terms: Adenocarcinoma; Amines; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Cell Line; Fluorouracil; Humans; Norfloxacin; Receptors, Estrogen; Rhodamines; Molecular Structure; Fluconazole; Molecular Docking Simulation
  7. Fulltext Molecular docking, synthesis and biological significance of pyrimidine analogues as prospective antimicrobial and antiproliferative agents
    Kumar S, Kaushik A, Narasimhan B, Shah SAA, Lim SM, Ramasamy K, et al.
    BMC Chem, 2019 Dec;13(1):85.
    PMID: 31384832 DOI: 10.1186/s13065-019-0601-z
    Pyrimidine nucleus is a significant pharmacophore that exhibited excellent pharmacological activities. A series of pyrimidine scaffolds was synthesized and its chemical structures were confirmed by physicochemical and spectral analysis. The synthesized compounds were evaluated for their antimicrobial potential towards Gram positive and negative bacteria as well as fungal species. They were also assessed for their anticancer activity toward a human colorectal carcinoma cell line (HCT116). Whilst results of antimicrobial potential revealed that compounds Ax2, Ax3, Ax8 and Ax14 exhibited better activity against tested microorganisms, the results of antiproliferative activity indicated that compounds Ax7 and Ax10 showed excellent activity against HCT116. Further, the molecular docking of pyrimidine derivatives Ax1, Ax9 and Ax10 with CDK8 (PDB id: 5FGK) protein indicated that moderate to better docking results within the binding pocket. Compounds Ax8 and Ax10 having significant antimicrobial and anticancer activities may be selected as lead compounds for the development of novel antimicrobial and anticancer agent, respectively.
    MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Cell Line; Fungi; Humans; Pyrimidines; Colorectal Neoplasms; Molecular Docking Simulation
  8. Fulltext In-silico molecular design of heterocyclic benzimidazole scaffolds as prospective anticancer agents
    Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.
    BMC Chem, 2019 Dec;13(1):90.
    PMID: 31384837 DOI: 10.1186/s13065-019-0608-5
    Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro v11.5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds 12, 16, N9, W20 and Z24 displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds 16, N9 and W20 have significant results within the close agreement of the Lipinski's rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
  9. Studies of Beauty Suppression via Nonprompt D^{0} Mesons in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Jul 12;123(2):022001.
    PMID: 31386524 DOI: 10.1103/PhysRevLett.123.022001
    The transverse momentum spectra of D^{0} mesons from b hadron decays are measured at midrapidity (|y|<1) in pp and Pb-Pb collisions at a nucleon-nucleon center of mass energy of 5.02 TeV with the CMS detector at the LHC. The D^{0} mesons from b hadron decays are distinguished from prompt D^{0} mesons by their decay topologies. In Pb-Pb collisions, the B→D^{0} yield is found to be suppressed in the measured p_{T} range from 2 to 100  GeV/c as compared to pp collisions. The suppression is weaker than that of prompt D^{0} mesons and charged hadrons for p_{T} around 10  GeV/c. While theoretical calculations incorporating partonic energy loss in the quark-gluon plasma can successfully describe the measured B→D^{0} suppression at higher p_{T}, the data show an indication of larger suppression than the model predictions in the range of 2
    MeSH terms: Lead; Mesons; Plasma; United States; Physical Phenomena; Nucleons
  10. FDG-PET predicted unfavorable tumor histology in living donor liver transplant recipients; a retrospective cohort study
    Ling LL, Hsu CC, Yong CC, Elsarawy AM, Chan YC, Wang CC, et al.
    Int J Surg, 2019 Sep;69:124-131.
    PMID: 31386913 DOI: 10.1016/j.ijsu.2019.07.035
    BACKGROUND: Tumor histology affects outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC). This study explores the association between F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and tumor histology in living donor liver transplantation (LDLT) recipients and their outcome.

    MATERIALS AND METHODS: Two hundred fifty-eight patients with primary liver tumors who underwent FDG-PET before LDLT were enrolled in this retrospective study. Unfavorable tumor histology was defined as primary liver tumor other than a well- or moderately differentiated HCC. Thirteen patients had unfavorable tumor histology, including 2 poorly differentiated HCC, 2 sarcomatoid HCC, 5 combined hepatocellular cholangiocarcinoma, 3 intrahepatic cholangiocarcinoma, and 1 hilar cholangiocarcinoma.

    RESULTS: FDG-PET positivity was significantly associated with unfavorable tumor histology (P < 0.001). Both FDG-PET positivity and unfavorable tumor histology were significant independent predictors of tumor recurrence and overall survival. In a subgroup analysis of patients with FDG-PET-positive tumors, unfavorable tumor histology was a significant independent predictor of tumor recurrence and overall survival. High FDG uptake (tumor to non-tumor uptake ratio ≥ 2) was a significant predictor of unfavorable tumor histology. Patients with high FDG uptake and/or unfavorable tumors had significantly higher 3-year cumulative recurrence rate (70.8% versus 26.2%, P = 0.004) and worse 3-year overall survival (34.1% versus 70.8%, P = 0.012) compared to those with low FDG uptake favorable tumors.

    CONCLUSIONS: The expression of FDG-PET is highly associated with histology of explanted HCC and predicts the recurrence. FDG-PET-positive tumors with high FDG uptake may be considered contraindication for LDLT due to high recurrence rate except when pathology proves favorable histology.

    MeSH terms: Adult; Aged; Female; Carcinoma, Hepatocellular/pathology; Carcinoma, Hepatocellular/surgery*; Humans; Liver Neoplasms/pathology; Liver Neoplasms/surgery*; Male; Middle Aged; Retrospective Studies; Radiopharmaceuticals*; Living Donors*; Fluorodeoxyglucose F18*; Positron-Emission Tomography/methods*
  11. Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies
    Taha M, Sultan S, Imran S, Rahim F, Zaman K, Wadood A, et al.
    Bioorg Med Chem, 2019 09 15;27(18):4081-4088.
    PMID: 31378594 DOI: 10.1016/j.bmc.2019.07.035
    In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1-25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization.
    MeSH terms: Diabetes Mellitus/drug therapy*; Humans; Quinolines/chemical synthesis*; Structure-Activity Relationship; Molecular Docking Simulation/methods*
  12. Fulltext Comment on: Managing tooth pain in general practice
    Ngeow WC, Chai WL
    Singapore Med J, 2019 07;60(7):383.
    PMID: 31378826 DOI: 10.11622/smedj.2019078
    MeSH terms: Family Practice; Humans; Pain; General Practice*; Pain Management*
  13. Fulltext An Assessment of Heavy Metals Toxicity in Asian Clam, Corbicula fluminea, from Mekong River, Pa Sak River, and Lopburi River, Thailand
    Sow AY, Dee KH, Lee SW, Eh Rak AAL
    ScientificWorldJournal, 2019;2019:1615298.
    PMID: 31379469 DOI: 10.1155/2019/1615298
    High population density and economic development attributing to the changes in water quality in Pa Sak River, Lopburi River, and Mekong River have attracted great attention. This research aimed to determine the pollution of heavy metals in collected clams at three different study sites. Bioaccumulation of heavy metals in Asian clam (Corbicula fluminea) may be likely to cause serious health effects on human beings. The clams sampled from three different rivers (Mekong, Pa Sak, and Lopburi) from Thailand were analyzed for the presence of heavy metals (Zn, Cu, Cd, Cr, Mn, and Pb) with an air-acetylene flame atomic absorption spectrophotometer (AAS). Among the heavy metals studied, Zn was recorded as having the highest concentration (127.33-163.65 μg/g) among the three rivers. The observed mean concentration of Cu was in the range of 84.61-127.15 μg/g followed by Mn (13.96-100.63 μg/g), Cr (5.79-15.00 μg/g), Pb (3.43-8.55 μg/g), and Cd (0.88-1.95 μg/g). Overall, Asian clam from Pa Sak River was found to contain high concentrations of Zn, Cu, Cd, Cr, and Pb compared to Mekong and Lopburi River.
    MeSH terms: Animals; Environmental Monitoring*; Fresh Water; Thailand; Metals, Heavy/toxicity*; Rivers*; Corbicula/drug effects; Corbicula/metabolism*
  14. Fulltext Seasonal Dynamics, Record of Ticks Infesting Humans, Wild and Domestic Animals and Molecular Phylogeny of Rhipicephalus microplus in Khyber Pakhtunkhwa Pakistan
    Ali A, Khan MA, Zahid H, Yaseen PM, Qayash Khan M, Nawab J, et al.
    Front Physiol, 2019;10:793.
    PMID: 31379587 DOI: 10.3389/fphys.2019.00793
    Although ticks prevalent in various agro-systems of Pakistan are associated with economic losses, information is still missing about the tick's diversity, hosts they infest, seasonal dynamics and molecular phylogeny of Rhipicephalus microplus in Khyber Pakhtunkhwa (KP) Pakistan. This study for the first time enlisted ticks infesting diverse hosts including humans in various regions of KP. A total of 8,641 ticks were collected across the northern, southern and central regions of KP and were morpho-taxonomically categorized into six genera comprising 17 species, R. microplus (n = 3,584, 42%), Hyalomma anatolicum (n = 2,253, 27%), Argas persicus (n = 1,342, 16%), Hya. impeltatum (n = 586, 7%), R. turanicus (n = 161, 2%), R. haemaphysaloides (n = 142, 2%), R. annulatus (n = 132, 2%), Hae. montgomeryi (n = 123, 1.4%), Hya. marginatum (n = 110, 1.3%), R. sanguineus (n = 34, 0.4%), and Hae. longicornis (n = 31, 0.4%). Ticks infesting wild animals included Amblyomma gervaisi, Amb. exornatum, Amb. latum, Dermacentor marginatus, and Hae. indica, while ticks collected from humans included R. microplus, R. annulatus, Hya. anatolicum, Hya. marginatum, and Hae. punctata. The overall prevalence of ticks infesting domestic animals was 69.4% (536/772). Among animal hosts, cattle were found highly infested (87.2%, 157/180) followed by buffalos (79%, 91/114), domestic fowls (74.7%, 112/150), goats (68.3%, 82/120), dogs (66.7%, 32/48), horses (61.3%, 49/80), and sheep (16.3%, 13/80). Analysis revealed that the tick burden significantly differed among domestic animals and was found to be high in cattle, followed by buffalos, goats, sheep, domestic fowl, dogs, and horses. Seasonal patterns of ticks distribution showed highest prevalance in July, August, and September due to the prevailing high temperature and humidity during these months. The phylogenetic analysis of cattle tick R. microplus based on partial mitochondrial cytochrome oxidase subunit I (COX1), 16S ribosomal RNA (16S rRNA) and internal transcribed spacer 2 (ITS2) sequences, revealed that R. microplus prevalent in this region belongs to clade C which include ticks originating from Bangladesh, Malaysia, and India. Further large scale studies across the country are necessary to explore the molecular and cross breeding aspects at the geographical overlapping of various tick species and their associated pathogens to facilitate designing control strategies as well as awareness against tick infestation in the region.
  15. Fulltext Erratum to "Double-Blind, Randomized, Three-Armed, Placebo-Controlled, Clinical Investigation to Evaluate the Benefit and Tolerability of Two Dosages of IQP-AE-103 in Reducing Body Weight in Overweight and Moderately Obese Subjects"
    Uebelhack R, Bongartz U, Seibt S, Bothe G, Chong PW, De Costa P, et al.
    J Obes, 2019 07 11;2019:6189724.
    PMID: 31380115 DOI: 10.1155/2019/6189724
    [This corrects the article DOI: 10.1155/2019/3412952.].
    MeSH terms: Humans
  16. Fulltext Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics
    Jan R, Chaudhry GE
    Adv Pharm Bull, 2019 Jun;9(2):205-218.
    PMID: 31380246 DOI: 10.15171/apb.2019.024
    Various physiological processes involve appropriate tissue developmental process and homeostasis - the pathogenesis of several diseases connected with deregulatory apoptosis process. Apoptosis plays a crucial role in maintaining a balance between cell death and division, evasion of apoptosis results in the uncontrolled multiplication of cells leading to different diseases such as cancer. Currently, the development of apoptosis targeting anticancer drugs has gained much interest since cell death induced by apoptosis causes minimal inflammation. The understanding of complexities of apoptosis mechanism and how apoptosis is evolved by tumor cells to oppose cell death has focused research into the new strategies designed to induce apoptosis in cancer cells. This review focused on the underlying mechanism of apoptosis and the dysregulation of apoptosis modulators involved in the extrinsic and intrinsic apoptotic pathway, which include death receptors (DRs) proteins, cellular FLICE inhibitory proteins (c-FLIP), anti-apoptotic Bcl-2 proteins, inhibitors of apoptosis proteins (IAPs), tumor suppressor (p53) in cancer cells along with various current clinical approaches aimed to selectively induce apoptosis in cancer cells.
    MeSH terms: Antineoplastic Agents; Homeostasis; Inflammation; Neoplasms; Physiological Phenomena; Signal Transduction; Tumor Suppressor Protein p53; Apoptosis; Receptors, Death Domain; CASP8 and FADD-Like Apoptosis Regulating Protein
  17. Fulltext 3D Microfluidic Bone Tumor Microenvironment Comprised of Hydroxyapatite/Fibrin Composite
    Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.
    Front Bioeng Biotechnol, 2019;7:168.
    PMID: 31380359 DOI: 10.3389/fbioe.2019.00168
    Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
    MeSH terms: Bone Neoplasms; Cell Movement; Cell Survival; Drug Evaluation, Preclinical; Extracellular Matrix; Fibrin; Prognosis; Stomach Neoplasms; Colorectal Neoplasms; Stromal Cells; Durapatite; Paracrine Communication; Microfluidics; Cell Proliferation; Tumor Microenvironment
  18. Fulltext Spinopelvic Fixation Supplemented With Gullwing Plate for Multiplanar Sacral Fracture With Spinopelvic Dissociation: A Case Series With Short Term Follow Up
    Mohd Asihin MA, Bajuri MY, Ahmad AR, Ganaisan PK, Fazir M, Salim AA
    Front Surg, 2019;6:42.
    PMID: 31380389 DOI: 10.3389/fsurg.2019.00042
    We describe a series of three patients who sustained multiplanar sacral fracture with spinopelvic dissociation treated with bilateral triangle osteosynthesis supplemented with a gullwing plate. Multiplanar sacral fracture causes the sacrum to divide into two parts which in severe cases, fracture displacement results in neurological injury. Spinopelvic fixation supplemented with a gullwing plate surgical treatment is still a viable option with an acceptable outcome. The average waiting time prior to surgery is 3 weeks.
    MeSH terms: Bone Plates; Fracture Fixation, Internal; Humans; Sacrum; Spinal Fractures; Fractures, Bone
  19. Fulltext Gold Nanorod Integrated Electrochemical Sensing for Hyperglycaemia on Interdigitated Electrode
    Zheng S, Zhang H, Lakshmipriya T, Gopinath SCB, Yang N
    Biomed Res Int, 2019;2019:9726967.
    PMID: 31380444 DOI: 10.1155/2019/9726967
    Gestational diabetes (hyperglycaemia) is an elevated blood sugar level diagnosed during the period of pregnancy and affects the baby's health. Hyperglycaemia has been found within the gestational weeks between 24 and 28, and the foetus has also the possibility of getting out prior to this test frame; it causes excessive birth weight, early birth, low-blood sugar level, respiratory distress syndrome, and type-2 diabetes to the mother. It creates a mandatory situation to identify the hyperglycaemia at least during the pregnancy weeks from 18 to 20. Further, a continuous monitoring of the level of glucose is necessary for the proper delivery. In this work, a method is introduced for glucose detection at 0.06 mg/mL, assisted by gold nanorod (GNR)-conjugated glucose oxidase (GOx) on interdigitated electrode sensor. In the absence of GNR, GOx shows the limit of glucose detection to be 0.25 mg/mL. Moreover, with GOx-GNR the reactions of all the glucose concentrations have recorded higher levels of the current from the baseline. With the specificity analysis, it was found that the glucose only reacts with GOx-GNR and discriminates other sugars efficiently. This method of detection is useful to diagnose and continuously monitor the glucose level during the pregnancy period.
    MeSH terms: Blood Glucose/isolation & purification*; Blood Glucose/chemistry; Enzymes, Immobilized/chemistry; Female; Glucose Oxidase/chemistry; Gold/chemistry; Humans; Pregnancy; Biosensing Techniques*; Diabetes, Gestational/blood*; Diabetes, Gestational/pathology; Nanotubes/chemistry*
  20. Fulltext Analgesia and Anaesthesia Management of Labour and Caesarean Delivery for a Parturient with Paramyotonia Congenita
    Najid NM, Razak TA, Günaydın DB
    Turk J Anaesthesiol Reanim, 2019 Aug;47(4):345-347.
    PMID: 31380517 DOI: 10.5152/TJAR.2019.69094
    Anaesthetic management in paramyotonia congenita (PC) or 'paradoxical myotonia' poses perioperative challenges to the anaesthesiologists both in obstetric and non-obstetric surgical patients. There are only a few case reports on the anaesthesia management particularly in the obstetric population. Therefore, we aimed to present the management of analgesia of labour and emergency caesarean delivery for a 26-year-old parturient with PC.
    MeSH terms: Analgesia; Anesthesia; Anesthetics; Cesarean Section; Female; Humans; Labor, Obstetric; Myotonia; Pregnancy; Myotonic Disorders; Pain Management
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