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  1. Tan SL, Halcovitch NR, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2019 Aug 01;75(Pt 8):1133-1139.
    PMID: 31417779 DOI: 10.1107/S2056989019009551
    The asymmetric unit of the title 1:1 solvate, C14H14N4O2·C6H6 [systematic name of the oxalamide mol-ecule: N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide], comprises a half mol-ecule of each constituent as each is disposed about a centre of inversion. In the oxalamide mol-ecule, the central C2N2O2 atoms are planar (r.m.s. deviation = 0.0006 Å). An intra-molecular amide-N-H⋯O(amide) hydrogen bond is evident, which gives rise to an S(5) loop. Overall, the mol-ecule adopts an anti-periplanar disposition of the pyridyl rings, and an orthogonal relationship is evident between the central plane and each terminal pyridyl ring [dihedral angle = 86.89 (3)°]. In the crystal, supra-molecular layers parallel to (10) are generated owing the formation of amide-N-H⋯N(pyrid-yl) hydrogen bonds. The layers stack encompassing benzene mol-ecules which provide the links between layers via methyl-ene-C-H⋯π(benzene) and benzene-C-H⋯π(pyrid-yl) inter-actions. The specified contacts are indicated in an analysis of the calculated Hirshfeld surfaces. The energy of stabilization provided by the conventional hydrogen bonding (approximately 40 kJ mol-1; electrostatic forces) is just over double that by the C-H⋯π contacts (dispersion forces).
  2. Tan W, Abd Ghani F, Seong Lim CT
    Indian J Nephrol, 2019 8 20;29(4):288-290.
    PMID: 31423065 DOI: 10.4103/ijn.IJN_153_18
    Acute renal cortical necrosis (ACN) is a potentially fatal renal condition. Our objective is to report a case of ACN in a young man who had developed premature atherosclerotic vascular disease and required intermittent hemodialysis support. His renal biopsy showed diffuse cortical necrosis. Subsequently, 2 weeks after the renal insult, he developed a cardioembolic stroke and was anticoagulated with low-molecular-weight heparin. Thrombophilia screen revealed elevated serum homocystein and he was treated with folate supplement and vitamin B12 injection. With these treatments, he had partial renal recovery and became dialysis independent. In conclusion, this is a rare case of ACN, which may have occurred as a complication of hyperhomocysteinemia.
  3. Moriya S, Tan VP, Yee AK, Parhar IS
    Neurosci Lett, 2019 08 24;708:134330.
    PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330
    In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.
  4. Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
  5. Teoh PY, Tan GC, Mahsin H, Wong YP
    Malays J Pathol, 2019 Aug;41(2):125-132.
    PMID: 31427547
    INTRODUCTION: Androgen receptor (AR) is the most frequently expressed biomarker in all subtypes of breast carcinoma. Triple negative breast carcinoma (TNBC) is breast carcinoma that lacks oestrogen and progesterone receptors immunoexpression as well as absence of HER2/neu gene amplification. This makes targeted therapy not feasible in this cancer and hence has poorer prognosis. Detecting AR expression could be another milestone in the management of TNBC, as AR is a prognostic, predictive marker and potential index for targeted treatment. This study aimed to assess expression of AR in TNBC by immunohistochemistry and its association with clinicopathological parameters.

    METHODS: We analysed the expression of AR in 97 TNBC cases from Penang General Hospital for a period of 3 years (2014 to 2017). Androgen receptor immunoreactivity was considered positive if ≥ 1% of tumour cells nuclei were stained irrespective of staining intensity.

    RESULTS: The prevalence of AR expression in TNBC was 31% (30/97), with the proportion of AR-positive tumour cells ranged from 1% to 90%. These include 23 invasive carcinomas, no special type (NST) and 7 other invasive carcinoma subtypes (papillary, lobular, clear cell and medullary carcinomas). Sixty-seven cases (69%) that showed AR immunonegativity were invasive carcinomas, NST (n=60), clear cell carcinoma (n=1) and metaplastic carcinoma (n=6). Androgen receptor immunoexpression was inversely correlated with tumour grade (p=0.016), but not the tumour stage, tumour size and nodal status.

    CONCLUSION: AR is expressed in about one-third of TNBC and loss of AR immunoexpression does not predict adverse clinical outcomes. Larger cohorts for better characterisation of the role of AR immunoexpression in TNBC are warranted.

  6. Tan SY, Visvanathan S, Abu Hassan R, Khan M
    Front Oncol, 2019;9:1335.
    PMID: 31850220 DOI: 10.3389/fonc.2019.01335
    Hepatitis B virus (HBV) is causally linked to hepatocellular injury and cell death, which are followed by hepatocellular carcinoma (HCC) after a long latent period. The HBV derived X protein (HBX) is the most potent carcinogenic factor for HCC, however, the molecular mechanism of HBX-induced transformation of hepatic cells in HCC is poorly understood. We have shown that nuclear receptor co-repressor (NCoR) is essential for the spatial repression of global transcription by the promyelocytic leukemia oncogenic domains (PODs), a frequent target of viral oncoproteins like HBX and that disintegration of PODs due to misfolded conformation dependent loss (MCDL) of NCoR is linked to promyelocytic and monocytic acute myeloid leukemia (AML). Given the key role of NCoR in cellular homeostasis across various tissue subtypes, we hypothesized that HBX-induced MCDL of NCoR might be linked to HCC through similar mechanism. Based on this hypothesis, the conformation of NCoR in HCC derived tumor cells and primary human tissue sections were analyzed and a selective MCDL of NCoR in HBX positive HCC cells was identified. HBX triggered the misfolding of NCoR through ubiquitination, followed by its degradation by autophagy, thus suggesting a cross talk between ubiquitin proteasome system (UPS) and autophagy lysosomal pathway (ALP) in MCDL of NCoR in HBX positive HCC cells. SiRNA-induced NCoR ablation selectively impaired the growth and survival of HBX positive HCC cells, suggesting a role of MCDL in the growth and survival of HBX positive HCC cells. These finding identify a possible crosstalk between UPS and ALP in the misfolding and loss of NCoR in HBX positive HCC cells and suggest a role of autophagic recycling of misfolded NCoR in the activation of oncogenic metabolic signaling in HCC. The misfolded NCoR reported in this study represents a novel conformation based molecular target which could be valuable in the design and development of tumor cell specific diagnostic and therapeutic approach for HBX positive HCC.
  7. Jeevanandam J, Tan KX, Danquah MK, Guo H, Turgeson A
    Biotechnol J, 2020 Mar;15(3):e1900368.
    PMID: 31840436 DOI: 10.1002/biot.201900368
    Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non-targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer-target binding results from several inter-molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer-mediated receptor targeting in targeted cancer therapy. MD simulation offers real-time analysis of the molecular drivers of the aptamer-receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.
  8. Mosavat M, Omar SZ, Jamalpour S, Tan PC
    J Diabetes Res, 2020;2020:9072492.
    PMID: 32090124 DOI: 10.1155/2020/9072492
    Background: Defects in incretin have been shown to be related to the pathogenesis of type 2 diabetes. Whether such a deficiency happens in gestational diabetes mellitus (GDM) remains to be confirmed. We assessed the association of fasting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) with GDM. We also studied the longitudinal circulation of these peptides during pregnancy and afterwards.

    Methods: 53 women with GDM (30 managed with diet only (GDM-diet) and 23 treated with insulin (GDM-insulin)) and 43 pregnant women with normal glucose tolerance (NGDM) were studied, with GIP and GLP-1 levels measured at 24-28 weeks (E1), prior (E2) and after (E3) delivery, and postpuerperium (E4).

    Results: Basal GIP was shown to be low in GDM groups compared to NGDM in E1, and in E4 for GDM-diet. GLP-1 was low in GDM groups during pregnancy and afterwards. At E1, serum GIP and GLP-1 were inversely associated with GDM and participants with lower levels of GIP (<0.23 ng/mL) and GLP-1 (<0.38 ng/mL) had a 6 (95% CI 2.5-14.5)- and 7.6 (95% CI 3.0-19.1)-fold higher risk of developing GDM compared with the higher level, respectively. In the postpuerperium, when there is a drop in β-cell function, participants with previous GDM (pGDM) presented lower GLP-1 (in both GDM subgroups) and lower GIP in GDM-diet subgroup compared to controls.

    Conclusion: There is an independent, inverse association between fasting incretins and higher risk of GDM. Furthermore, lowered levels of these peptides may play an important role in the abnormality of glucose regulation following pregnancy.

  9. Liu F, Wang S, Liu B, Wang Y, Tan W
    Cells, 2020 02 24;9(2).
    PMID: 32102363 DOI: 10.3390/cells9020511
    Psoriasis is a skin disease that is characterized by a high degree of inflammation caused by immune dysfunction. (R)-salbutamol is a bronchodilator for asthma and was reported to alleviate immune system reactions in several diseases. In this study, using imiquimod (IMQ)-induced mouse psoriasis-like dermatitis model, we evaluated the therapeutic effects of (R)-salbutamol in psoriasis in vivo, and explored the metabolic pathway involved. The results showed that, compared with IMQ group, (R)-salbutamol treatment significantly ameliorated psoriasis, reversed the suppressive effects of IMQ on differentiation, extreme keratinocyte proliferation, and infiltration of inflammatory cells. Enzyme-linked immunosorbent assays (ELISA) showed that (R)-salbutamol markedly reduced the plasma levels of IL-17. Cell analysis using flow cytometry showed that (R)-salbutamol decreased the proportion of CD4+ Th17+ T cells (Th17), whereas it increased the percentage of CD25+ Foxp3+ regulatory T cells (Tregs) in the spleens. (R)-salbutamol also decreased the weight ratio of spleen to body. Furthermore, untargeted metabolomics showed that (R)-salbutamol affected three metabolic pathways, including (i) arachidonic acid metabolism, (ii) sphingolipid metabolism, and (iii) glycerophospholipid metabolism. These results demonstrated that (R)-salbutamol can alleviate IMQ-induced psoriasis through regulating Th17/Tregs cell response and glycerophospholipid metabolism. It may provide a new use of (R)-salbutamol in the management of psoriasis.
  10. Chew MX, Teoh PY, Wong YP, Tan GC
    Malays J Pathol, 2019 Dec;41(3):365-368.
    PMID: 31901924
    INTRODUCTION: Umbilical cord abnormalities include short cord, long cord, knots, hyper-coiling, hypo-coiling, stricture, single umbilical artery, supernumerary umbilical vessels, cystic and vascular malformation, and abnormal insertion of cord like velamentous and furcate insertions. We report a case of intrauterine death in a fetus with multiple umbilical cord strictures and vascular thrombosis.

    CASE REPORT: A 35-year-old woman delivered a stillborn female fetus at 33 weeks of gestation. No fetal anomaly was detected. Examination of the umbilical cord showed multiple strictures, located 4.5 cm and 20 cm from the placental insertion site. Microscopically, the stricture site showed Wharton's jelly being replaced by fibrosis with presence of vascular thrombosis.

    DISCUSSION: Umbilical cord stricture is uncommon and has been described to be associated with intrauterine fetal death and a possibility of recurrent. There is a need to counsel the parents and close fetal surveillance in subsequent pregnancy is advise since the risk of recurrent remains uncertain.

  11. Tan SL, Jotani MM, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2020 Feb 01;76(Pt 2):155-161.
    PMID: 32071739 DOI: 10.1107/S2056989019017328
    In the title compound, C12H15N3O5S, a tris-ubstituted thio-urea derivative, the central CN2S chromophore is almost planar (r.m.s. deviation = 0.018 Å) and the pendant hy-droxy-ethyl groups lie to either side of this plane. While to a first approximation the thione-S and carbonyl-O atoms lie to the same side of the mol-ecule, the S-C-N-C torsion angle of -47.8 (2)° indicates a considerable twist. As one of the hy-droxy-ethyl groups is orientated towards the thio-amide residue, an intra-molecular N-H⋯O hydrogen bond is formed which leads to an S(7) loop. A further twist in the mol-ecule is indicated by the dihedral angle of 65.87 (7)° between the planes through the CN2S chromophore and the 4-nitro-benzene ring. There is a close match between the experimental and gas-phase, geometry-optimized (DFT) mol-ecular structures. In the crystal, O-H⋯O and O-H⋯S hydrogen bonds give rise to supra-molecular layers propagating in the ab plane. The connections between layers to consolidate the three-dimensional architecture are of the type C-H⋯O, C-H⋯S and nitro-O⋯π. The nature of the supra-molecular association has been further analysed by a study of the calculated Hirshfeld surfaces, non-covalent inter-action plots and computational chemistry, all of which point to the significant influence and energy of stabilization provided by the conventional hydrogen bonds.
  12. Tan SN, Gendeh HS, Gendeh BS, Ramzisham AR
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1683-1686.
    PMID: 31763224 DOI: 10.1007/s12070-015-0918-4
    Hemangioma is a disease of head and neck commonly, but its presence in the nasal cavity or sinus is rare. It is a form of benign tumour of vascular origin consisting of predominantly blood vessels. It can be categorized into capillary, cavernous and mixed type in accordance to its histopathology features. Retrospectively, we reviewed five cases of nasal hemangioma presenting at University Kebangsaan Malaysia Medical Center (UKMMC) between September 2007 and May 2015. Information on the patients age, gender, ethnicity, clinical symptoms, imaging findings (if available), treatment modalities were collected retrospectively for analysis. Five patients were analysed. Females were more affected than male with ratio of 4:1. All patients presented with unilateral lobular capillary hemangioma of the nasal cavity with 60 % (3/5) of the lesions on the right side and 40 % (2/5) on the left side. The common symptoms at presentation were epitaxis and nasal obstruction (5/5, 100 %), followed by rhinorrhea (3/5, 60 %) and facial pain (1/5, 20 %). All the patients underwent a surgical excision of the hemangioma. The five patients had no recurrence on subsequent follow ups. Computed tomography of paranasal sinuses can be performed to exclude bony erosions. Endoscopic sinus haemangioma excision provide good visualisation and better outcomes. In conclusion, nasal hemangioma should always be differential diagnosis for nasal lesions and surgical excision is still the preferred first line treatment.
  13. Tan CY, Sekiguchi Y, Goh KJ, Kuwabara S, Shahrizaila N
    Clin Neurophysiol, 2020 01;131(1):63-69.
    PMID: 31751842 DOI: 10.1016/j.clinph.2019.09.025
    OBJECTIVE: We aimed to develop a model that can predict the probabilities of acute inflammatory demyelinating polyneuropathy (AIDP) based on nerve conduction studies (NCS) done within eight weeks.

    METHODS: The derivation cohort included 90 Malaysian GBS patients with two sets of NCS performed early (1-20days) and late (3-8 weeks). Potential predictors of AIDP were considered in univariate and multivariate logistic regression models to develop a predictive model. The model was externally validated in 102 Japanese GBS patients.

    RESULTS: Median motor conduction velocity (MCV), ulnar distal motor latency (DML) and abnormal ulnar/normal sural pattern were independently associated with AIDP at both timepoints (median MCV: p = 0.038, p = 0.014; ulnar DML: p = 0.002, p = 0.003; sural sparing: p = 0.033, p = 0.009). There was good discrimination of AIDP (area under the curve (AUC) 0.86-0.89) and this was valid in the validation cohort (AUC 0.74-0.94). Scores ranged from 0 to 6, and corresponded to AIDP probabilities of 15-98% at early NCS and 6-100% at late NCS.

    CONCLUSION: The probabilities of AIDP could be reliably predicted based on median MCV, ulnar DML and ulnar/sural sparing pattern that were determined at early and late stages of GBS.

    SIGNIFICANCE: A simple and valid model was developed which can accurately predict the probability of AIDP.

  14. Andiappan V, Benjamin MFD, Tan RR, Ng DKS
    Heliyon, 2019 Oct;5(10):e02594.
    PMID: 31720447 DOI: 10.1016/j.heliyon.2019.e02594
    Designers of energy systems often face challenges in balancing the trade-off between cost and reliability. In literature, several papers have presented mathematical models for optimizing the reliability and cost of energy systems. However, the previous models only addressed reliability implicitly, i.e., based on availability and maintenance planning. Others focused on allocation of reliability based on individual equipment requirements via non-linear models that require high computational effort. This work proposes a novel mixed-integer linear programming (MILP) model that combines the use of both input-output (I-O) modelling and linearized parallel system reliability expressions. The proposed MILP model can optimize the design and reliability of energy systems based on equipment function and operating capacity. The model allocates equipment with sufficient reliability to meet system functional requirements and determines the required capacity. A simple pedagogical example is presented in this work to illustrate the features of proposed MILP model. The MILP model is then applied to a polygeneration case study consisting of two scenarios. In the first scenario, the polygeneration system was optimized based on specified reliability requirements. The technologies chosen for Scenario 1 were the CHP module, reverse osmosis unit and vapour compression chiller. The total annualized cost (TAC) for Scenario 1 was 53.3 US$ million/year. In the second scenario, the minimum reliability level for heat production was increased. The corresponding results indicated that an additional auxiliary boiler must be operated to meet the new requirements. The resulting TAC for the Scenario 2 was 5.3% higher than in the first scenario.
  15. Tan MK, Japir R, Chung AYC, Robillard T
    Zootaxa, 2019 Jun 19;4619(2):zootaxa.4619.2.9.
    PMID: 31716308 DOI: 10.11646/zootaxa.4619.2.9
    Orthoptera from Sandakan, Sabah are relatively understudied compared to some other parts of Borneo, and lack of information of species there can impede our understanding of the origins and biodiversity of orthopterans in Borneo and, in general, Southeast Asia. Based on a recent orthopteran survey in Sandakan, one new species of Lebinthus Stål is described: Lebinthus sandakan sp. nov. The male calling song of this new species is also presented. The calling song of Cardiodactylus borneoe Robillard Gorochov, 2014 is also described for the first time.
  16. Yeo H, Tan CH, Chong CS, Lam-Phua SG
    Zootaxa, 2019 Jul 01;4624(3):zootaxa.4624.3.9.
    PMID: 31716216 DOI: 10.11646/zootaxa.4624.3.9
    Accurate identification of mosquitoes is crucial for the management and control of vector species. Although Singapore is a tropical country with high mosquito diversity, there are no identification keys specific to its mosquito fauna. An illustrated identification key to the genera of the adult female mosquitoes of Singapore is presented. Twenty genera are characterized and two genera found in Malaysia, Culiseta and Topomyia, are also included. The key will aid non-taxonomically trained operational officers in adult mosquito identification. The key to the genera provides the first crucial step in the process to species identification.
  17. Fu TL, Ong KC, Tan SH, Wong KT
    J. Neuropathol. Exp. Neurol., 2019 12 01;78(12):1160-1170.
    PMID: 31675093 DOI: 10.1093/jnen/nlz103
    Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1-5 days postinfection (dpi) study, demonstrated focal viral antigens/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection.
  18. Ise Y, Woo SP, Tan SH, Fujita T
    Zootaxa, 2019 Aug 20;4657(3):zootaxa.4657.3.3.
    PMID: 31716770 DOI: 10.11646/zootaxa.4657.3.3
    Two new species of thinly encrusting sponge Hamacantha (Demospongiae, Merliida, Hamacanthidae) are described from Japan. Hamacantha (Vomerula) mamoi sp. nov. was collected from Sagami Bay, and Hamacantha (Vomerula) umisachii sp. nov. from off Hachijo Island. This is the first record of Hamacantha and the Hamacanthidae from Japan. H. (V.) mamoi sp. nov. is characterized by having styles, two types of diancistras and one of sigmas. Only two known species have the same spicule composition: H. (V.) acerata Lévi, 1993 and H. (V.) esperioides Ridley Dendy, 1886, described from New Caledonia, and south-west Africa and south-east South America, respectively. H. (V.) acerata has larger diancistras and much smaller sigmas compared with those of H. (V.) mamoi sp. nov. H. (V.) esperioides can be separated by having larger styles and smaller sigmas than those of H. (V.) mamoi sp. nov. H. (V.) umisachii sp. nov is characterized by having styles, diancistras, cyrtancistra-like diancistras and sigmas. Hamacantha (V.) carteri Topsent, 1904 seems to have similar spicule composition, however the size of all spicule types is different.
  19. Tan CS, Loh YC, Tew WY, Yam MF
    Inflammopharmacology, 2020 Aug;28(4):869-875.
    PMID: 31925617 DOI: 10.1007/s10787-019-00682-6
    Resveratrol is found in numerous plant-based foods and beverages and is known to have an impact on the cardiovascular system. The aim of this study was to investigate the vasorelaxant effect of resveratrol and its underlying mechanisms by employing an aortic ring assay model. Resveratrol caused relaxation of aortic rings that had been precontracted with phenylephrine in the presence of endothelium or with potassium chloride in endothelium-intact aortic rings. The vasorelaxant effect was decreased in the absence of an endothelium. The mechanisms underlying the vasorelaxant effect of resveratrol were determined through the addition of antagonists. In the presence of the endothelium, indomethacin (a nonselective cyclooxygenase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor), Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), tetraethylammonium (TEA, nonselective calcium activator potassium channel blocker), 4-aminopyridine (4-AP, voltage-dependent K+ channel blocker), barium chloride (BaCl2, inwardly rectifying K+ channel blocker), glibenclamide (non-specific ATP-sensitive K+ channel blocker) and propranolol (β-adrenergic receptor blocker) led to a significant reduction in the vasorelaxation effect induced by resveratrol. Resveratrol was also found to reduce Ca2+ release from the sarcoplasmic reticulum and block calcium channels. In conclusion, resveratrol targets multiple signalling pathways for exerting its vasorelaxant effects in the rat aortic ring model in both the presence and absence of endothelium.
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