Displaying publications 1 - 20 of 51 in total

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  1. Ling WC, Mustafa MR, Vanhoutte PM, Murugan DD
    Vascul Pharmacol, 2018 03;102:11-20.
    PMID: 28552746 DOI: 10.1016/j.vph.2017.05.003
    AIM: Endothelial dysfunction accompanied by an increase in oxidative stress is a key event leading to hypertension. As dietary nitrite has been reported to exert antihypertensive effect, the present study investigated whether chronic oral administration of sodium nitrite improves vascular function in conduit and resistance arteries of hypertensive animals with elevated oxidative stress.

    METHODS: Sodium nitrite (50mg/L) was given to angiotensin II-infused hypertensive C57BL/6J (eight to ten weeks old) mice for two weeks in the drinking water. Arterial systolic blood pressure was measured using the tail-cuff method. Vascular responsiveness of isolated aortae and renal arteries was studied in wire myographs. The level of nitrite in the plasma and the cyclic guanosine monophosphate (cGMP) content in the arterial wall were determined using commercially available kits. The production of reactive oxygen species (ROS) and the presence of proteins (nitrotyrosine, NOx-2 and NOx-4) involved in ROS generation were evaluated with dihydroethidium (DHE) fluorescence and by Western blotting, respectively.

    RESULTS: Chronic administration of sodium nitrite for two weeks to mice with angiotensin II-induced hypertension decreased systolic arterial blood pressure, reversed endothelial dysfunction, increased plasma nitrite level as well as vascular cGMP content. In addition, sodium nitrite treatment also decreased the elevated nitrotyrosine and NOx-4 protein level in angiotensin II-infused hypertensive mice.

    CONCLUSIONS: The present study demonstrates that chronic treatment of hypertensive mice with sodium nitrite improves impaired endothelium function in conduit and resistance vessels in addition to its antihypertensive effect, partly through inhibition of ROS production.

  2. Paul M, Kalimuthu S, Banu C, Marimuthu S
    Trauma Case Rep, 2018 Dec;18:5-7.
    PMID: 30505922 DOI: 10.1016/j.tcr.2018.11.002
    Penetrative neck injury can cause potentially fatal damage to the neck. Removing those fully embedded small foreign bodies secondary to ballistic trauma can be technically challenging. Neck exploration under direct vision may cause more local tissue damage or dislodge the foreign body further. We discussed a case where a small foreign body embedded in the neck caused by ballistic trauma. Successful removal of the foreign body guided by rigid endoscope thru the neck wound was also discussed as a useful tool as it was not ferromagnetic and image intensifier was not available.
  3. Hussaini HM, Angel CM, Speight PM, Firth NA, Rich AM
    Head Neck Pathol, 2012 Dec;6(4):471-5.
    PMID: 22427262 DOI: 10.1007/s12105-012-0350-y
    The hallmark of the histology of epithelial-myoepithelial carcinoma (EMC) is the presence of a regular repetitive mixture of bilayered duct-like structures with an outer layer of myoepithelial cells and inner ductal epithelial cells. Clear cell change in the myoepithelial component is common, but clearing of both cell types, giving an impression of a monocellular neoplasm, is rare. A parotid biopsy was received from an 83-year-old male and subject to routine histologic processing for conventional staining and immunohistochemistry. The encapsulated tumour was composed of sheets of PAS/diastase negative clear cells, separated by fibrous septae. The clear myoepithelial cells were positive for S-100 protein, SMA, and p63 and negative for CK19 and surrounded CK19-positive luminal cells. It is important to utilise immunohistochemistry to differentiate this tumour from others with a similar histologic pattern. Information about the behaviour of the double-clear EMC is limited since there are few cases reported.
  4. Mokhtar SS, Vanhoutte PM, Leung SW, Suppian R, Yusof MI, Rasool AH
    Eur J Pharmacol, 2016 Feb 15;773:78-84.
    PMID: 26825543 DOI: 10.1016/j.ejphar.2016.01.013
    Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 ± 2.48% versus 85.05 ± 3.15%). Incubation with the combination of non-selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 ± 5.84% versus 68.39 ± 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 ± 6.74% versus 34.16 ± 4.59%) (prostacyclin; 15.85 ± 3.27% versus 17.23 ± 3.75%)]. Endothelium-independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction.
  5. Yu F, Bracken CP, Pillman KA, Lawrence DM, Goodall GJ, Callen DF, et al.
    PLoS One, 2015;10(6):e0129190.
    PMID: 26061048 DOI: 10.1371/journal.pone.0129190
    p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs) are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.
  6. Khan AS, Ur Rehman S, Ahmad S, AlMaimouni YK, Alzamil MAS, Dummer PMH
    Int Endod J, 2021 Oct;54(10):1819-1839.
    PMID: 34196006 DOI: 10.1111/iej.13595
    AIM: The International Endodontic Journal (IEJ) has served as a platform for research and clinical practice in Endodontics since 1967. This study provides a bibliographic analysis and overview of the publications that have appeared in the IEJ from 1967 to 2020.

    METHODOLOGY: A literature search was performed in Elsevier's Scopus database to locate all the publications of the International Endodontic Journal. Various bibliometric software packages including the open-source visualization software Gephi and Biblioshiny (version 2.0) were employed for data visualization and analysis.

    RESULTS: A total of 3739 records with citation and bibliographic details were selected and retrieved to allow a bibliometric analysis to be performed. The bibliometric analysis indicates that the IEJ has grown both in terms of productivity and influence. Over time, the journal has been associated with an increase in the number of manuscripts published and the citations they have attracted, but with minor downward fluctuations in citations in the last few years. Bibliographic coupling of the IEJ articles revealed that the major research themes published in the journal include 'endodontics', 'root canal treatment', 'calcium hydroxide', 'apical periodontitis', 'mineral trioxide aggregate', 'microbiology', 'cyclic fatigue', 'cone-beam computed tomography' and 'micro-computed tomography'. Authors affiliated to institutions in the UK were the major contributors to the journal and were linked with other countries such as Brazil, USA and Malaysia. The largest number of publications were from the University of São Paulo, Brazil.

    CONCLUSION: The IEJ is one of the leading journals in Endodontology and has been providing a platform for innovative research and clinical reports for more than 50 years. Publications have been associated with a wide range of authors, institutions and countries around the world.

  7. Ling WC, Murugan DD, Lau YS, Vanhoutte PM, Mustafa MR
    Sci Rep, 2016 09 12;6:33048.
    PMID: 27616322 DOI: 10.1038/srep33048
    Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS.
  8. Lee WH, Loo CY, Leong CR, Young PM, Traini D, Rohanizadeh R
    Expert Opin Drug Deliv, 2017 08;14(8):937-957.
    PMID: 27759437 DOI: 10.1080/17425247.2017.1247804
    INTRODUCTION: The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer. Areas covered: This review focuses on the recent advances in the functionalization of nanocarriers with specific ligands, including antibodies, transferrin, folate, and peptides to overcome MDR cancer. The limitations of effective ligand-functionalized nanoparticles as well as therapeutic successes in ligand targeting are covered in the review. Expert opinion: Targeting MDR tumors with ligand-functionalized nanoparticles is a promising approach to improve the treatment of cancer. With this approach, higher drug concentrations at targeted sites would be achieved with lower dosage frequencies and reduced side effects in comparison to existing formulations of chemotherapeutic drugs. However, potential toxicities and immunological responses to ligands should be carefully reviewed for viable options in for future MDR cancer treatment.
  9. Garcia S, Bhatt DL, Gallagher M, Jneid H, Kaufman J, Palevsky PM, et al.
    JACC Cardiovasc Interv, 2018 11 26;11(22):2254-2261.
    PMID: 30466822 DOI: 10.1016/j.jcin.2018.07.044
    OBJECTIVES: The aim of this study was to compare intravenous (IV) sodium bicarbonate with IV sodium chloride and oral acetylcysteine with placebo for the prevention of contrast-associated acute kidney injury (CAAKI) and intermediate-term adverse outcomes.

    BACKGROUND: Data are conflicting on the optimal strategy to reduce CAAKI and related complications after percutaneous coronary intervention (PCI).

    METHODS: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) trial used a 2 × 2 factorial design to randomize 5,177 patients with stage III or IV chronic kidney disease undergoing angiography to IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and 5 days of oral acetylcysteine or placebo. A subgroup analysis was conducted of the efficacy of these interventions in patients who underwent PCI during the study angiographic examination. The primary endpoint was a composite of death, need for dialysis, or persistent kidney impairment at 90 days; CAAKI was a secondary endpoint.

    RESULTS: A total of 1,161 PRESERVE patients (mean age 69 ± 8 years) underwent PCI. The median estimated glomerular filtration rate was 50.7 ml/min/1.73 m2 (interquartile range: 41.7 to 60.1 ml/min/1.73 m2), and 952 patients (82%) had diabetes mellitus. The primary endpoint occurred in 15 of 568 patients (2.6%) in the IV sodium bicarbonate group and 24 of 593 patients (4.0%) in the IV sodium chloride group (odds ratio: 0.64; 95% confidence interval: 0.33 to 1.24; p for interaction = 0.41) and in 23 of 598 patients (3.8%) in the acetylcysteine group and 16 of 563 patients (2.8%) in the placebo group (odds ratio: 1.37; 95% confidence interval: 0.71 to 2.62; p for interaction = 0.29). There were no significant between-group differences in the rates of CAAKI.

    CONCLUSIONS: Among patients with CKD undergoing PCI, there was no benefit of IV sodium bicarbonate over IV sodium chloride or of acetylcysteine over placebo for the prevention of CAAKI or intermediate-term adverse outcomes.

  10. Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D
    Adv Drug Deliv Rev, 2018 08;133:107-130.
    PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012
    Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
  11. Halali S, Halali D, Barlow HS, Molleman F, Kodandaramaiah U, Brakefield PM, et al.
    J Evol Biol, 2021 09;34(9):1362-1375.
    PMID: 34173293 DOI: 10.1111/jeb.13895
    Phenotypic plasticity in heterogeneous environments can provide tight environment-phenotype matching. However, the prerequisite is a reliable environmental cue(s) that enables organisms to use current environmental information to induce the development of a phenotype with high fitness in a forthcoming environment. Here, we quantify predictability in the timing of precipitation and temperature change to examine how this is associated with seasonal polyphenism in tropical Mycalesina butterflies. Seasonal precipitation in the tropics typically results in distinct selective environments, the wet and dry seasons, and changes in temperature can be a major environmental cue. We sampled communities of Mycalesina butterflies from two seasonal locations and one aseasonal location. Quantifying environmental predictability using wavelet analysis and Colwell's indices confirmed a strong periodicity of precipitation over a 12-month period at both seasonal locations compared to the aseasonal one. However, temperature seasonality and periodicity differed between the two seasonal locations. We further show that: (a) most females from both seasonal locations synchronize their reproduction with the seasons by breeding in the wet season but arresting reproduction in the dry season. In contrast, all species breed throughout the year in the aseasonal location and (b) species from the seasonal locations, but not those from the aseasonal location, exhibited polyphenism in wing pattern traits (eyespot size). We conclude that seasonal precipitation and its predictability are primary factors shaping the evolution of polyphenism in Mycalesina butterflies, and populations or species secondarily evolve local adaptations for cue use that depend on the local variation in the environment.
  12. Nagendrababu V, Faggion CM, Pulikkotil SJ, Alatta A, Dummer PMH
    Int Endod J, 2022 Jan 26.
    PMID: 35080025 DOI: 10.1111/iej.13693
    AIM: The aims of the study were to assess the methodological quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR 2) tool, and to evaluate the overall confidence in the results of the individual reviews included in the analysis.

    METHODOLOGY: Systematic reviews with NMAs within the specialty of Endodontics published in English were identified from the PubMed, EbBSCOhost and SCOPUS databases from inception to July 2021. Two reviewers were involved independently in the selection of the reviews, data extraction, methodological quality assessment and overall confidence rating. Disagreements were resolved by discussion between the reviewers to achieve consensus; if disagreements persisted, a third reviewer made the final decision. The methodological quality of the included NMAs was appraised using the AMSTAR 2 checklist, which contains 16 items. The reviewers scored each item - 'Yes' - when the item was fully addressed, 'Partial Yes' - when the item was not fully addressed, or 'No' - when the item was not addressed. The overall confidence in the results of each review was classified as 'High', 'Moderate', 'Low' or 'Critically low' based on the criteria reported by the AMSTAR 2 developers.

    RESULTS: Twelve systematic reviews with NMAs were included. All the NMAs adequately reported Item 1 ("Did the research questions and inclusion criteria for the review include the components of PICO?"), Item 8 ("Did the review authors describe the included studies in adequate detail?"), Item 9 ("Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?") and Item 16 ("Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?") , whereas only one NMA reported Item 10 adequately ("Did the review authors report on the sources of funding for the studies included in the review?"). The overall confidence in the results of eight reviews was categorised as "Critically low", one review was "Low", two reviews were "Moderate" and one review was "High".

    CONCLUSION: The overall confidence in the results for the majority of systematic reviews with NMAs in Endodontics was judged to be 'Critically low' as their methodological quality was below the necessary standard. AMSTAR 2 and PRISMA for NMA guidelines are available to guide authors to produce high quality systematic reviews with NMAs and for Editors and peer-reviewers when assessing submissions to journals.

  13. Choy KW, Lau YS, Murugan D, Vanhoutte PM, Mustafa MR
    J. Pharmacol. Exp. Ther., 2018 03;364(3):420-432.
    PMID: 29259041 DOI: 10.1124/jpet.117.245217
    Inflammatory injury of the endothelium leads to apoptosis and endothelial dysfunction. The current study explored the effect and mechanisms of paeonol in inflammation-induced apoptosis and endothelial dysfunction induced by lipopolysaccharides (LPSs). The effects of paeonol on LPS-induced inflammatory injury were assessed by Western blotting, flow cytometry and reactive oxygen species (ROS) measurement in human umbilical vein endothelial cells (HUVECs) and C57BL/6J mice. Vascular reactivity of isolated mouse aortae was examined using wire myographs. The exposure of HUVECs to LPS increased the protein presence of Toll-like receptor 4 (TLR4), bone morphogenic protein 4 (BMP4), BMP receptor type 1A, nicotinamide adenine dinucleotide phosphate oxidase subunit 2, mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), and cleaved caspase 3, as well as decreased it in phosphorylated endothelial nitric oxide synthase; these effects were prevented by treatment with paeonol. Similarly, cotreatment with paeonol reversed BMP4-induced apoptosis in HUVECs. Relaxation in response to the endothelium-dependent vasodilator acetylcholine were impaired in mouse aortae after exposure to LPSs; this endothelial dysfunction was reversed by cotreatment with paeonol, noggin (a BMP4 inhibitor), TAK242 (TLR4 antagonist), apocynin (an ROS scavenger), MAPK inhibitors, and AG (an iNOS inhibitor). BMP4 small interfering RNAs (siRNAs) abolished LPS-induced upregulation of BMP4 and cleaved caspase 3 protein, but not in cells treated with TLR4 siRNA and vice versa. The silencing of TLR4 and BMP4 abolished the inhibitory effects of paeonol on LPS-induced activation of cleaved caspase 3. The present results demonstrate that paeonol reduces LPS-induced endothelial dysfunction and apoptosis by inhibiting TLR4 and BMP4 signaling independently.
  14. Ahmed HMA, Nagendrababu V, Duncan HF, Peters OA, Dummer PMH
    Int Endod J, 2023 Jul;56(7):788-791.
    PMID: 37300405 DOI: 10.1111/iej.13918
  15. Jong HL, Mustafa MR, Vanhoutte PM, AbuBakar S, Wong PF
    Physiol Genomics, 2013 Apr 1;45(7):256-67.
    PMID: 23362143 DOI: 10.1152/physiolgenomics.00071.2012
    MicroRNAs (miRNAs) regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in human umbilical vein endothelial cells (HUVECs). An integrated miRNA and gene profiling approach revealed that hsa-miR-299-3p is upregulated in senescent HUVECs compared with the young cells, and one of its target genes could be IGF1. IGF1 was upregulated in senescent compared with young HUVECs, and knockdown of hsa-miR-299-3p dose-dependently increased the mRNA expression of IGF1, more significantly observed in the presenescent cells (passage 19) compared with the senescent cells (passage 25). Knockdown of hsa-miR-299-3p also resulted in significant reduction in the percentage of cells positively stained for senescence-associated β-galactosidase and increases in cell viability measured by MTT assay but marginal increases in cell proliferation and cell migration capacity measured by real-time growth kinetics analysis. Moreover, knockdown of hsa-miR-299-3p also increased proliferation of cells treated with H2O2 to induce senescence. These findings suggest that hsa-miR-299-3p may delay or protect against replicative senescence by improving the metabolic activity of the senesced cells but does not stimulate growth of the remaining cells in senescent cultures. Hence, these findings provide an early insight into the role of hsa-miR-299-3p in the modulation of replicative senescence in HUVECs.
  16. Nagendrababu V, Narasimhan S, Faggion CM, Dharmarajan L, Jacob PS, Gopinath VK, et al.
    Clin Oral Investig, 2023 Jul;27(7):3437-3445.
    PMID: 36914841 DOI: 10.1007/s00784-023-04948-w
    OBJECTIVES: To evaluate the reporting quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) for NMA checklist.

    METHODS: The current investigation extends a recently published study in the International Endodontic Journal (Nagendrababu V, Faggion Jr CM, Pulikkotil SJ, Alatta A, Dummer PM Methodological assessment and overall confidence in the results of systematic reviews with network meta-analyses in Endodontics. International Endodontic Journal 2022;55:393-404) that assessed the methodological quality of systematic reviews with NMAs in Endodontics using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) tool. In the present study, the PRISMA for NMA checklist with 32 items was used to assess the reporting quality of the systematic reviews with NMAs (n = 12). Two independent assessors assigned '1' when an item was completely addressed, '0.5' when it was partially addressed, and '0' when it was not addressed. Disagreements were resolved through reviewer discussion until consensus was reached. If conflicts persisted, a third reviewer made the final decision. The PRISMA for NMA scores were shared with the relevant authors of the individual reviews to reduce the likelihood of misinterpretation and verify the scores assigned. The results for each individual item of the PRISMA-NMA items were calculated by summing the individual scores awarded; the maximum score for each item was 12.

    RESULTS: All the systematic reviews with NMAs adequately reported the following items: Title, Introduction section (Objectives), Methods section (Eligibility criteria and Information sources), Results section (Study selection, Study characteristics and Risk of bias within studies), and Discussion section (Summary of evidence). The items that were reported least often were the "geometry of the network" and "the summary of network geometry" with only 2 manuscripts (17%) including these items.

    CONCLUSION: A number of the items in the PRISMA-NMA checklist were adequately addressed in the NMAs; however, none adequately reported all the PRISMA-NMA items. The inadequacies of published NMAs that have been identified should be taken into consideration by authors of NMAs in Endodontics and by editors when managing the peer review process. In future, researchers who are writing systematic reviews with NMAs should comply with the PRISMA-NMA checklist.

    CLINICAL RELEVANCE: None of the included systematic reviews with NMA adequately reported all the PRISMA-NMA items. Inadequate reporting of a systematic review with NMA increases the possibility that it will provide invalid results. Therefore, authors should follow the PRISMA-NMA guidelines when reporting systematic reviews with NMA in Endodontics.

  17. Linton RE, Daker M, Khoo AS, Choo DCY, Viljoen M, Neilsen PM
    Oncol Lett, 2021 Jul;22(1):514.
    PMID: 33986874 DOI: 10.3892/ol.2021.12775
    Nasopharyngeal carcinoma (NPC) is a cancer of the epithelial cells lining the nasopharynx. The incidence of NPC has a distinct geographical distribution, mainly affecting the Chinese population of Southern China. In Malaysia, this cancer is exceptionally prevalent among males. There is a high incidence rate of NPC among the Bidayuh natives in Sarawak, Malaysia. Other than epidemiology reports, there has not been an article describing plausible cancer risk factors contributing to NPC within this native group. Researchers are still trying to understand the reasons the Bidayuh and Southern Chinese are highly susceptible to NPC. This article discusses the risk factors of developing NPC: Epstein-Barr virus infection, genetic predisposition, diet, environmental exposure and tobacco smoking. There is a need to improve the understanding of the role of risk factors to identify new ways to prevent cancer, especially among high-risk groups.
  18. Loh WM, Ling WC, Murugan DD, Lau YS, Achike FI, Vanhoutte PM, et al.
    Vascul Pharmacol, 2015 Aug;71:151-8.
    PMID: 25869508 DOI: 10.1016/j.vph.2015.03.011
    Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1μM) for 30min prior to the assessment of angiotensin II-induced contractions (0.1nM-10μM) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress.
  19. Ling WC, Lau YS, Murugan DD, Vanhoutte PM, Mustafa MR
    Vascul Pharmacol, 2015 Nov;74:87-92.
    PMID: 26044183 DOI: 10.1016/j.vph.2015.05.014
    Ingestion of dietary nitrites lowers arterial blood pressure in experimental animals and in humans. However, the exact mechanism underlying the hypotensive effect of nitrite remains unclear. The present study compared nitrite-induced responses in rings (with or without endothelium) of aortae of 18-20weeks old Wistar-Kyoto Rats (WKY) and spontaneously hypertensive (SHR) rats and investigated the underlying mechanism. Relaxations of aortae from WKY and SHR to increasing concentrations (1nM-100μM) of sodium nitrite (NaNO2) were determined during sustained contractions to phenylephrine, in the absence and presence of pharmacological agents. The nitrite-induced relaxations were concentration-dependent and larger in SHR than in WKY aortic rings. Inhibition of endothelial nitric oxide synthase (eNOS) and the absence of endothelium decreased nitrite-induced relaxations in both WKY and SHR aortae, indicating the role of endothelium-derived nitric oxide (NO) in the response. The involvement of eNOS was further confirmed by increases in phosphorylation of eNOS at ser1177 in HUVEC cells following treatment with sodium nitrite. The presence of NO scavengers decreased the relaxation to nitrite in both WKY and SHR preparations while inhibition of soluble guanylyl cyclase (sGC) abolished the response, indicating that besides producing NO, nitrite also induces relaxation by directly activating the enzyme. Thus, the present study demonstrates that the sensitivity to exogenous nitrite is increased in the aorta of the SHR compared to that of the WKY. The endothelium-dependent component of the relaxation to nitrite involves activation of eNOS with production of endothelium-derived NO, while the endothelium-independent component is due to stimulation of sGC.
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