Chapter 1: "Permanent Maxillary and Mandibular Incisors"\n Chapter 2: "The Permanent Maxillary and Mandibular Premolar Teeth"\n Chapter 3: "Dental Anatomical Features and Caries: A Relationship to be Investigated"\n Chapter 4: "Anatomy Applied to Block Anaesthesia"\n Chapter 5: "Treatment Considerations for Missing Teeth"\n Chapter 6: "Anatomical and Functional Restoration of the Compromised Occlusion: From Theory to Materials"\n Chapter 7: "Evaluation of the Anatomy of the Lower First Premolar"\n Chapter 8: "A Comparative Study of the Validity and Reproducibility of Mesiodistal Tooth Size and Dental Arch with the iTero Intraoral Scanner and the Traditional Method"\n Chapter 9: "Identification of Lower Central Incisors"\n The book is aimed toward dentists and can also be well used in education and research.',isbn:"978-1-78923-511-1",printIsbn:"978-1-78923-510-4",pdfIsbn:"978-1-83881-247-8",doi:"10.5772/65542",price:119,priceEur:129,priceUsd:155,slug:"dental-anatomy",numberOfPages:204,isOpenForSubmission:!1,isInWos:null,hash:"445cd419d97f339f2b6514c742e6b050",bookSignature:"Bağdagül Helvacioğlu Kivanç",publishedDate:"August 1st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5814.jpg",numberOfDownloads:7259,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:3,hasAltmetrics:0,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 4th 2016",dateEndSecondStepPublish:"October 25th 2016",dateEndThirdStepPublish:"July 16th 2017",dateEndFourthStepPublish:"August 16th 2017",dateEndFifthStepPublish:"October 16th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"178570",title:"Dr.",name:"Bağdagül",middleName:null,surname:"Helvacıoğlu Kıvanç",slug:"bagdagul-helvacioglu-kivanc",fullName:"Bağdagül Helvacıoğlu Kıvanç",profilePictureURL:"https://mts.intechopen.com/storage/users/178570/images/7646_n.jpg",biography:"Bağdagül Helvacıoğlu Kıvanç is a dentist, a teacher, a researcher and a scientist in the field of Endodontics. 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\r\n\tFood security, sustainable agriculture, and poverty alleviation are the key themes of the 2030 United Nations’ Sustainable Development Goals (UN-SDGs). These are directly linked with agricultural mechanization, automation and robotics, high-efficiency irrigation systems, farm energy systems, post-harvest handling and processing, wastewater management, and the associated sustainable bio environment. Such agricultural, biological, and environmental engineering studies are the need of the 21st century, particularly from the viewpoint of the agricultural water–energy–food security nexus. Moreover, the wide range and interdisciplinary nature of research for agricultural engineering and technologies and system as well as the proliferation and technological advancement in agricultural engineering technologies will be the focus of this book. It will include engineering technologies and applications related to farm mechanization, farm energy and environment, smart farming, intelligent agriculture, conservation agriculture, on-farm irrigation, precision agriculture, food processing and storage, livestock and poultry sheds, wastewater management, etc. The chapters will comprise of original research, review, case studies, and/or recent progress/scenario in the above-mentioned research areas. \r\n\t
",isbn:"978-1-83881-922-4",printIsbn:"978-1-83881-921-7",pdfIsbn:"978-1-83881-923-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"dcfc52d92f694b0848977a3c11c13d00",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",keywords:"Agricultural Engineering, Technologies, Application, Sustainable Agriculture, Information Technology in Agriculture, Food Security, Renewable Energies, Precision Farming, Smart Agriculture, Farm Mechanization, Robotics, Post Harvest Technologies",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 25th 2020",dateEndSecondStepPublish:"December 23rd 2020",dateEndThirdStepPublish:"February 21st 2021",dateEndFourthStepPublish:"May 12th 2021",dateEndFifthStepPublish:"July 11th 2021",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ahmad is a researcher in the field of agricultural mechanization and agricultural equipment engineering, in-charge of Farm Machinery Design Laboratory at Bahauddin Zakariya University, with expertise in modeling and simulation. 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\n
1. Background
\n
Endometriosis is a common estrogen dependent and progesterone resistant disease of unknown cause characterized by growth of endometrial cells outside the uterine cavity [1]. It is estimated that 6–11% of all women are affected by endometriosis reaching an estimated 176 million women globally [2]. A chronic painful disease [3], endometriosis causes substantial health distress and interference with normal activities including work resulting in an average loss of 10.8 h/week from work [2] all leading to diminished quality of life (QOL) for affected women and their families. Chronic pelvic pain and infertility are common symptoms of endometriosis that bring women with this disease to seek medical attention. Approximately 71–87% of all women experiencing chronic pelvic pain and 50% of infertile women are diagnosed with endometriosis [4]. Thus, women with endometriosis report significant health distress and interference with normal activities including work and leisure time activities all leading to a deleterious effect upon women’s social functioning, emotional well-being, employment, and vitality [5].
\n
An important obstacle to the timely diagnosis and effective management of endometriosis is the lack of a simple diagnostic test. Diagnosis has been reported to be delayed by between 6 and 12 years with an average of 9 years from the onset of symptoms to definitive diagnosis [6]. Hence, identification of a clinical tool for the diagnosis of endometriosis has become a high priority research objective [2, 7, 8]. Health care providers and patients face a number of challenges in arriving at a diagnosis of endometriosis including: early age at onset of symptoms, normalization of pain by primary care providers, and suppression of symptoms through intermittent use of oral contraceptive pills [9]. Symptoms of endometriosis are shared with many other diseases including autoimmune diseases, cancer, irritable bowel syndrome (IBS), and musculoskeletal abnormalities. Therefore, an ideal biomarker of endometriosis must differentiate between endometriosis and other explanations for patient symptoms. In addition, clinical markers should be as minimally invasive as possible, affordable and convenient to use with the added benefit of providing insight into potential treatment response. Furthermore, the ideal biomarker must provide equivalent or similar outcome measures of sensitivity, specificity, positive, and negative predictive values to laparoscopy.
\n
Currently, the gold standard for diagnosis remains visualization of endometriotic lesions typically by laparoscopy followed by histopathological confirmation of disease [10]. Current trends favoring the non-surgical diagnosis of endometriosis increase the pressure to identify novel clinical markers of endometriosis. Despite a plethora of biochemical differences in the peripheral circulation, peritoneal fluid, and endometrial tissues of women with endometriosis compared to healthy controls, no marker has been found with adequate sensitivity or specificity to challenge laparoscopy for the diagnosis of endometriosis whether used alone or in a panel of clinical markers [11, 12, 13, 14, 15, 16]. However, reports of promising results have been brought forward in the literature from which epigenetic markers are potentially the most exciting.
\n
\n
\n
2. Candidate clinical markers of endometriosis
\n
Multiple gene and protein expression levels have been documented in women with endometriosis compared to controls; however, none have yielded reliable clinical markers of disease. Recent studies investigating the mechanisms controlling gene expression have produced promising results. Several histone modifications have been associated with endometriosis. For example, endometriotic stromal cells (ESC) have a lower global acetylation level of H3, and histone deacetylases 1 and 2 (HDAC1 and HDAC2) were upregulated compared to women without endometriosis [17]. Furthermore, histone deacetylase inhibitor (HDACI) treatment promoted apoptosis by reactivating the silenced chromatin [18]. G-protein-coupled estrogen receptor (GPER) expression and proliferation of endometriotic cells was inhibited by treatment with the HDACI’s romidepsin and vorinostat [19]. These data suggest that histone modifications are involved in the pathophysiology of endometriosis and that HDACI’s are promising agents for endometriosis treatment. However, use of histone markers in the diagnosis of endometriosis has yet to be explored.
\n
Long-chain non-coding RNA (lnc-RNAs) are 200–100,000 bp RNA molecules which do not encode for protein, but are involved in transcriptional and post-transcriptional regulation of gene expression [20]. They are the most common non-coding RNAs and are involved in cell proliferation, differentiation, and apoptosis; all processes central in the pathobiology of endometriosis [21]. Some lnc-RNAs proposed as diagnostic markers of endometriosis include: H19 [22], CHL1-AS2 [23, 24], AC002454.1 [25], lncRNA SRA (steroid receptor RNA activator) [26], MALAT-1 [27], and LINC01279 [28]. Results of a recent study revealed the lnc-RNA are carried in circulating extracellular vesicles in women with endometriosis [29]. However, use of lnc-RNAs in the diagnosis of endometriosis has not been evaluated in a prospective study of women with symptoms suggestive of endometriosis with an independent validation step and thus their clinical utility remains uncertain.
\n
Several recent studies have documented aberrant expression of multiple microRNAs (miRNAs) in the eutopic and ectopic endometrium of women with endometriosis [30, 31, 32, 33, 34, 35, 36, 37]. miRNAs are short non-coding RNAs, 19–25 nucleotides long, that negatively regulate mRNA translation by repressing the protein translational machinery or degrading their target transcripts. Greater than 2000 mature human miRNA sequences have been identified and are thought to regulate approximately 50% of all protein coding genes. Multiple recent studies have documented differential microRNA (miRNA) expression in endometriotic tissues compared to eutopic endometrium of women with endometriosis and controls [33, 38, 39, 40]. miRNA are thought to hold promise as diagnostic biomarkers of disease because they are post-transcriptional regulators of gene expression that are stably expressed over time in bodily fluids and tissues [41]. Briefly, miRNA regulate protein expression through binding to and inhibiting the translation of mRNA transcripts into protein [42]. miRNAs are synthesized in the cytoplasm from nucleic hairpin intermediates (pre-miRNA) [43] which are then processed to yield mature miRNA that resist RNase degradation [41]. miRNA form an RNA-induced silencing complex (RISC) with Argonaute, Dicer, TAR RNA binding protein (TRBP) and protein activator of PKR (PACT) to post-transcriptionally regulate genes by binding to the 3′ region of the mRNA transcript and inhibiting translation [44].
\n
In the early 2000s, several studies proposed that circulating levels of miRNA are differentially expressed in women with endometriosis compared to controls and thus could have diagnostic value [30, 31, 45]. Different methods including in situ hybridization, targeted RT-PCR and several different screening platforms including miRNA based microarrays, next generation sequencing and bio-informatics followed by RT-PCR validation have subsequently revealed a broad spectrum of miRNAs that are differentially expressed in women with endometriosis compared to control groups [29, 30, 31, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56]. However, to date, only the results for hsa-miR-451a [47, 48], 199a-5p [31, 54] and hsa-miR-141-3p [31, 49] have been successfully replicated in more than one study (Table 1). For the vast majority of miRNAs, differential expression has only been reported in a single study or the results for a few miRNAs have not been replicated by other investigators. For example, circulating levels of hsa-miR-145 were lower in women with endometriosis compared to controls [31] whereas hsa-miR-145 levels did not differ [47] or were higher in women with endometriosis compared to the control groups [50]. We postulate that divergent results may be the consequence of different screening platforms and technologies used to identify candidate miRNA markers of disease [57, 58, 59] and control group characteristics. Moreover, we suggest that different reference material used to quantify circulating miRNA levels are an additional source of variation.
Summary of miRNA’s differentially expressed by microarray and RT-PCR in women with endometriosis (cases) compared to controls.
Direction could not be ascertained from the published report.
miRNA in bold have been replicated by at least one other group of investigators.
S = significant effect of menstrual cycle stage, NS = not significant, ND = not determined, NR = not reported, differential miR expression was either increased (↑) or decreased (↓) in women with endometriosis compared to controls.
\n
While RNU6 has been widely used in the general miRNA literature to normalize miRNA expression in tissue, abundance and stability of expression have not been evaluated for circulating miRNA expression in women with endometriosis. Furthermore, RNU6 has low stability and abundance that is greatly influenced by sample storage and processing and the Cp values of RNU6 are highly variable from miRNA Cp values [51, 60, 61]. Similarly, the abundance and stability of miR-16-5p levels in the serum of women with endometriosis is uncertain but variable from the Cp values of miRNA targets [51]. Furthermore, circulating levels of miR-16-5p are altered by inflammation and stress [62, 63] and thus we suggest that both RNU6 and miR-16-5p are not suitable for normalization of circulating miRNA levels in women with endometriosis.
\n
\n
\n
3. Effect of reference miRNA used to normalize results
\n
While serum RNU6 has been widely used as the reference miRNA in prior endometriosis studies [29, 31, 46, 47, 48, 54], its levels have previously been reported to be unstable, unreliable, and a poor reference for miRNA since it is not processed or protected in the same way as miRNA [61, 63]. Therefore, we suggest that choice of reference miRNA can influence ability to detect significant differences and the direction of significant differences elicited. Previous studies report that hsa-miR-451a is upregulated in women with endometriosis compared to symptomatic controls [47] and compared to both symptomatic and asymptomatic (healthy) control groups [48]. Both prior studies employed RNU6 as a reference. While hsa-miR-451a has been found to act as a tumor suppressor [64, 65], it is also a marker of hemolysis [66] and thus we suggest that care should be employed to exclude samples with hemolysis before analysis. The miRNA ratio of hsa-miR-451a and hsa-miR-23a-3p has been employed by others [56, 67] to monitor for sample hemolysis. Therefore, we suggest that hsa-miR-451a has limited value as a candidate marker of endometriosis.
\n
\n
\n
4. Effect of control group definition
\n
Several studies have employed healthy women as their control population [29, 45, 48, 49, 51, 55], thus allowing circulating miRNA levels in women with endometriosis to be compared to symptomatic and asymptomatic healthy control populations. While the majority of previous reports employed symptomatic controls [30, 31, 46, 47, 48, 49, 50, 51, 53, 54, 56], hsa-miR-16-5p [30, 51] RNU6 (the most common) reference material used to normalize miRNA expression [31, 46, 47, 48, 51, 54]; reference materials that are unsuitable for normalizing serum miRNA expression. In our experience, differential miRNA expression was dependent upon whether comparisons were made with asymptomatic compared to symptomatic controls. Therefore, we suggest that control group characteristics on the differential expression of candidate miRNA in women with endometriosis merits further investigation.
\n
While, lack of replication, absence of validation of results, and poor sensitivity and specificity currently limit the value of miRNA as diagnostic markers of endometriosis [51], we propose that usefulness of miRNA for the diagnosis of endometriosis cannot be evaluated without appropriate determination of appropriate reference miRNA.
\n
\n
\n
5. Future directions
\n
Although identification of clinical markers of endometriosis has long been sought, none has so far been suitable to displace laparoscopy as the gold standard for diagnosis. Endometriosis is a complex heterogenous disease with variable presentation whose symptoms are easily confused with other clinical problems. Since endometriosis is detectable with high frequency amongst asymptomatic women [68] surgical exclusion of disease in the control group is essential to prevent biasing results towards the null. Consequently, we suggest that control or reference group definition is important. Numerous prior studies reporting differential miRNA expression in women with endometriosis have employed asymptomatic women as their reference population [29, 45, 48, 49, 51, 55]. However, healthy women without symptoms of endometriosis and without evidence of endometriosis by laparoscopy (asymptomatic control) and symptomatic women without evidence of disease at the time of laparoscopy (symptomatic control) are functionally different, yet both groups continue to be employed as controls in contemporary studies. Results from our laboratory suggest that inclusion of asymptomatic controls can produce misleading results and thus speculate that restricting the control group to symptomatic controls in future studies may improve reproducibility of results. In addition to control group, we propose that the use of validated reference miRNA to normalize results also affects detection of levels of miRNA differentially expressed in women with endometriosis compared to controls.
\n
Having identified candidate miRNA for the diagnosis of endometriosis it will be important to determine their relationship with pelvic pain as well as response to treatment. In the absence of this data the potential prognostic value of candidate markers of endometriosis remains uncertain. We also propose that future studies with robust sample size will be needed to clarify the relationship between circulating miRNA levels and menstrual cycle phase. Studies reporting menstrual cycle stage and circulating miRNA levels are thus far have produced equivocal results [31, 46, 47, 48, 49, 51, 53, 56]. Furthermore, lesion type (endometrioma, peritoneal endometriosis, deep infiltrating endometriosis) are biologically distinct and thus a single clinical marker is unlikely to be dysregulated in all lesion types and thus a panel of markers may be more relevant. Furthermore, duration of disease and age of lesion may also present with functional differences. Therefore, discovery of clinical markers should describe the lesion types present in study participants. The influence of study participant age and body mass index are also important variables associated with pelvic pain and disease severity that are frequently not considered in analyses of clinical markers of endometriosis. Finally, the functional role of candidate markers in endometriosis has the potential to suggest therapeutic targets for additional research.
\n
\n
\n
6. Summary and conclusions
\n
Use of reference miRNA that may not be ideal for normalization of results may account for noted weaknesses in the literature. Use of validated reference miRNA markers and careful control of sample condition for potential confounders should improve study replication. Finally, although circulating miRNA levels have low variability in women with endometriosis, it will be necessary for discovery phases to include a large number of study participants to control for participant age, menstrual cycle stage, BMI, stage of disease, and type of lesions. Thus, we suggest that despite set-backs with reproducibility of results, it may be too soon to judge the diagnostic potential of miRNA.
\n
\n
Acknowledgments
\n
Funding support for this project was provided by a research operating grant (MOP142230) from the Canadian Institutes of Health Research to WGF. The authors are grateful to Ms. Annette Bullen for her assistance in study participant recruitment, access to clinical data, and sample collection. The assistance of the Endo@Mac surgical team (Drs. Nick Leyland, Sarah Scatollon, and Dustin Costescu) with access to study participants, staging of disease, and collection of blood samples is greatly appreciated.
\n
\n',keywords:"microRNA, miRNA, diagnosis, plasma, endometriosis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71151.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71151.xml",downloadPdfUrl:"/chapter/pdf-download/71151",previewPdfUrl:"/chapter/pdf-preview/71151",totalDownloads:135,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"October 25th 2019",dateReviewed:"January 22nd 2020",datePrePublished:"February 19th 2020",datePublished:null,dateFinished:"February 19th 2020",readingETA:"0",abstract:"Endometriosis is a common estrogen dependent and inflammatory disease affecting approximately 176 million women worldwide. Currently, the time between onset of symptoms and a definitive diagnosis has been reported by several international studies to range from 6 to 12 years. Presently, laparoscopic surgery followed by histopathological confirmation of lesions remains the gold standard for diagnosis. In part because of cost and invasiveness, current trends favor reduced laparoscopic surgeries in preference of the non-surgical diagnosis of endometriosis. However, the search for a clinical marker or markers of endometriosis that provide equal or similar sensitivity and specificity to laparoscopy has remained elusive. Thus, the search for a diagnostic test for the diagnosis of endometriosis continues to be a high priority research and clinical issue. Recent studies have reported favorable results with microRNA; however, lack of replication and absence of validation suggest that circulating miRNA may not be reliable for clinical use. Use of different screening platforms together with divergent methods may account for some of the lack or reproducibility in the literature. Herein we critically assess the recent literature and explore sources for discrepant findings. We suggest that prospective studies using validated reference miRNA to normalize results together with improved study design may yet reveal a suitable diagnostic marker or panel of markers for the diagnosis of endometriosis.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71151",risUrl:"/chapter/ris/71151",book:{slug:"endometriosis"},signatures:"Victoria Turpin, Anna Leonova, Sanjay K. Agarwal and Warren G. Foster",authors:null,sections:[{id:"sec_1",title:"1. Background",level:"1"},{id:"sec_2",title:"2. Candidate clinical markers of endometriosis",level:"1"},{id:"sec_3",title:"3. Effect of reference miRNA used to normalize results",level:"1"},{id:"sec_4",title:"4. Effect of control group definition",level:"1"},{id:"sec_5",title:"5. Future directions",level:"1"},{id:"sec_6",title:"6. Summary and conclusions",level:"1"},{id:"sec_7",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\nSampson J. 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Current Medicinal Chemistry. 2012;19(15):2406-2413\n'},{id:"B36",body:'\nBraza-Boils A, Mari-Alexandre J, Gilabert J, Sanchez-Izquierdo D, Espana F, Estelles A, et al. MicroRNA expression profile in endometriosis: Its relation to angiogenesis and fibrinolytic factors. Human Reproduction. 2014;29(5):978-988\n'},{id:"B37",body:'\nBraza-Boils A, Gilabert-Estelles J, Ramon LA, Gilabert J, Mari-Alexandre J, Chirivella M, et al. Peritoneal fluid reduces angiogenesis-related microRNA expression in cell cultures of endometrial and endometriotic tissues from women with endometriosis. PLoS ONE. 2013;8(4):e62370\n'},{id:"B38",body:'\nHaikalis ME, Wessels JM, Leyland NA, Agarwal SK, Foster WG. miRNA expression pattern differs depending on endometriosis lesion type. Biology of Reproduction. 2018;98(5):623-633\n'},{id:"B39",body:'\nBurney RO, Hamilton AE, Aghajanova L, Vo KC, Nezhat CN, Lessey BA, et al. MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis. Molecular Human Reproduction. 2009;15(10):625-631\n'},{id:"B40",body:'\nLaudanski P, Charkiewicz R, Tolwinska A, Szamatowicz J, Charkiewicz A, Niklinski J. Profiling of selected MicroRNAs in proliferative Eutopic endometrium of women with ovarian endometriosis. BioMed Research International. 2015;2015:760698\n'},{id:"B41",body:'\nChen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Research. 2008;18(10):997-1006\n'},{id:"B42",body:'\nBartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297\n'},{id:"B43",body:'\nLee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: Stepwise processing and subcellular localization. The EMBO Journal. 2002;21(17):4663-4670\n'},{id:"B44",body:'\nChendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436(7051):740-744\n'},{id:"B45",body:'\nSuryawanshi S, Vlad AM, Lin HM, Mantia-Smaldone G, Laskey R, Lee M, et al. Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer. Clinical Cancer Research. 2013;19(5):1213-1224\n'},{id:"B46",body:'\nCho S, Mutlu L, Grechukhina O, Taylor HS. Circulating microRNAs as potential biomarkers for endometriosis. Fertility and Sterility. 2015;103(5):1252-1260 e1251\n'},{id:"B47",body:'\nCosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS. Serum microRNAs as diagnostic markers of endometriosis: A comprehensive array-based analysis. Fertility and Sterility. 2016;106(2):402-409\n'},{id:"B48",body:'\nNothnick WB, Falcone T, Joshi N, Fazleabas AT, Graham A. Serum miR-451a levels are significantly elevated in women with endometriosis and recapitulated in baboons (Papio anubis) with experimentally-induced disease. Reproductive Sciences. 2017;24(8):1195-1202\n'},{id:"B49",body:'\nRekker K, Saare M, Roost AM, Kaart T, Soritsa D, Karro H, et al. Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time. Fertility and Sterility. 2015;104(4):938-946 e932\n'},{id:"B50",body:'\nBashti O, Noruzinia M, Garshasbi M, Abtahi M. miR-31 and miR-145 as potential non-invasive regulatory biomarkers in patients with endometriosis. Cell Journal. 2018;20(2):293\n'},{id:"B51",body:'\nNisenblat V, Sharkey DJ, Wang Z, Evans SF, Healey M, Ohlsson Teague EMC, et al. Plasma microRNAs display limited potential as diagnostic tools for endometriosis. The Journal of Clinical Endocrinology and Metabolism. 2019;104(6):1999-2022\n'},{id:"B52",body:'\nWang L, Huang W, Ren C, Zhao M, Jiang X, Fang X, et al. Analysis of serum microRNA profile by Solexa sequencing in women with endometriosis. Reproductive Sciences. 2016;23(10):1359-1370\n'},{id:"B53",body:'\nPateisky P, Pils D, Szabo L, Kuessel L, Husslein H, Schmitz A, et al. Hsa-miRNA-154-5p expression in plasma of endometriosis patients is a potential diagnostic marker for the disease. Reproductive Biomedicine Online. 2018;37(4):449-466\n'},{id:"B54",body:'\nMaged AM, Deeb WS, El Amir A, Zaki SS, El Sawah H, Al Mohamady M, et al. Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis. International Journal of Gynaecology and Obstetrics. 2018;141(1):14-19\n'},{id:"B55",body:'\nHsu CY, Hsieh TH, Tsai CF, Tsai HP, Chen HS, Chang Y, et al. miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. The Journal of Pathology. 2014;232(3):330-343\n'},{id:"B56",body:'\nVanhie A, O D, Peterse D, Beckers A, Cuéllar A, Fassbender A, et al. Plasma miRNAs as biomarkers for endometriosis. Human Reproduction. 2019;34(9):1650-1660\n'},{id:"B57",body:'\nMestdagh P, Hartmann N, Baeriswyl L, Andreasen D, Bernard N, Chen C, et al. Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nature Methods. 2014;11(8):809-815\n'},{id:"B58",body:'\nKok MGM, de Ronde MWJ, Moerland PD, Ruijter JM, Creemers EE, Pinto-Sietsma SJ. Small sample sizes in high-throughput miRNA screens: A common pitfall for the identification of miRNA biomarkers. Biomolecular Detection and Quantification. 2018;15:1-5\n'},{id:"B59",body:'\nPritchard CC, Cheng HH, Tewari M. MicroRNA profiling: Approaches and considerations. Nature Reviews. Genetics. 2012;13(5):358-369\n'},{id:"B60",body:'\nGraham A, Falcone T, Nothnick WB. The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Human Reproduction. 2015;30(3):642-652\n'},{id:"B61",body:'\nXiang M, Zeng Y, Yang R, Xu H, Chen Z, Zhong J, et al. U6 is not a suitable endogenous control for the quantification of circulating microRNAs. Biochemical and Biophysical Research Communications. 2014;454(1):210-214\n'},{id:"B62",body:'\nWang H, Zhang P, Chen W, Feng D, Jia Y, Xie LX. Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects. Clinical Chemistry and Laboratory Medicine. 2012;50(8):1423-1428\n'},{id:"B63",body:'\nKatsuura S, Kuwano Y, Yamagishi N, Kurokawa K, Kajita K, Akaike Y, et al. MicroRNAs miR-144/144* and miR-16 in peripheral blood are potential biomarkers for naturalistic stress in healthy Japanese medical students. Neuroscience Letters. 2012;516(1):79-84\n'},{id:"B64",body:'\nLiu G, Xu Z, Hao D. MicroRNA-451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor. Molecular Medicine Reports. 2016;13(3):2253-2260\n'},{id:"B65",body:'\nXu H, Mei Q , Shi L, Lu J, Zhao J, Fu Q . Tumor-suppressing effects of miR451 in human osteosarcoma. Cell Biochemistry and Biophysics. 2014;69(1):163-168\n'},{id:"B66",body:'\nShkurnikov MY, Knyazev EN, Fomicheva KA, Mikhailenko DS, Nyushko KM, Saribekyan EK, et al. Analysis of plasma microRNA associated with Hemolysis. Bulletin of Experimental Biology and Medicine. 2016;160(6):748-750\n'},{id:"B67",body:'\nBlondal T, Jensby Nielsen S, Baker A, Andreasen D, Mouritzen P, Wrang Teilum M, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59(1):S1-S6\n'},{id:"B68",body:'\nRawson JM. Prevalence of endometriosis in asymptomatic women. Journal of Reproductive Medicine. 1991;36(7):513-515\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Victoria Turpin",address:null,affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Canada
Department of Obstetrics and Gynecology, McMaster University, Canada
'},{corresp:null,contributorFullName:"Sanjay K. Agarwal",address:null,affiliation:'
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, United States of America
'},{corresp:"yes",contributorFullName:"Warren G. Foster",address:"fosterw@mcmaster.ca",affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Canada
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, United States of America
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1. Introduction
Diabetes mellitus (DM) is a chronic metabolic disorder that is not only affecting various populations worldwide but also poised on affecting the developing nations of the world much more than developed countries [1, 2]. The International Diabetes Foundation (IDF) reported a diagnosis of over 400 million people living with diabetes and postulated an estimated increase to over 600 million people by the year 2040 in a worldwide survey [3, 4]. The report also shows that diabetes accounts for a death every 6 seconds [3]. In a recent study, it was observed that the total reported cases of people affected by DM had increased by 10 million in the subsequent survey carried out by IDF over the next year [5].
DM is a heterogeneous metabolic disorder and is difficult to classify. However, DM has been categorised into three major types based on the pathologic process. Type 1 diabetes mellitus (T1DM), also known as childhood/early-onset diabetes or insulin-dependent DM, is characterised by insulin deficiency as a result of β-cell dysfunction, degeneration and degradation by the immune system [6]. Type 2 diabetes mellitus (T2DM), also known as adult/late-onset diabetes or non-insulin-dependent DM has insulin secretion and insulin resistance (IR) as its major characteristics [7]. Gestational diabetes mellitus (GDM) has glucose intolerance in pregnant women as its major characteristic. It is as a result of the β-cells inability to meet up with the insulin demand in pregnant women without a previous diagnosis of diabetes [8].
Diabetologists have a few other categories, such as tropical DM and Type 3 diabetes mellitus (T3DM). The former is thought to have a relationship with malnutrition [8], while the latter is a suggested mechanistic link to Alzheimer’s disease via inflammatory response and other mechanisms resulting in the pathophysiologic changes relating diabetes to dementia [3]. However, there is little information on the rarer forms of diabetes, such as secondary diabetes, mitochondrial diabetes, maturity-onset diabetes of the young, and latent autoimmune diabetes of adults [9].
1.1 Risk factors
Physical inactivity or sedentary lifestyle, excessive alcohol, overweight, obesity and unhealthy diet intake are modifiable DM risk factors [10]. Family history, hypertension, history of previously impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), advancing age, history of GDM, ethnicity and genetic makeup are some unmodifiable risk factors. However, various researchers have reported that novel risk factors such as short sleep duration [11], noise pollution [12] and environmental toxins [13] contribute to the causal pathways which lead to diabetes. Trade and agricultural production policies are thought to contribute to both individual and societal level risk factors [14].
2. Diabetes mellitus in Nigeria
2.1 Epidemiology
The transition from infectious diseases to non-communicable diseases as leading causes of death is fast becoming a growing epidemiological trend and public health dichotomy in Sub-Saharan African countries [15]. In Africa, there is a 1% estimated prevalence of diabetes in rural areas while in urban areas, the range is from 5–7% [16]. Nigeria accounts for about one-sixth of Africa’s population [1]. The national prevalence of diabetes, which was less than 1% between 1960 and 1990, has risen from 2.2% in 1997 to 5% in 2013 [17]. However, the current prevalence may currently be as high as between 8 and 10% [9], with 4.83% recorded for patients aged 20 and above, accounting for over 3 million people currently living with this condition [18]. This observation makes her the country with the highest number of people living with diabetes and IFG in Africa [19]. Epidemiological statistics show that Nigeria is responsible for one in every five reported sub-Saharan case of diabetes, with a steep increase in the prevalence of this disease from the rural areas to members of the high socio-economic population [9]. Continuous urbanisation, the increasing population and poor economy, will further drive the incidence and burden of diabetes upwards in Nigeria [1, 2, 20]. T2DM appears to be the majority of the DM burden in Nigeria with T1DM accounting for less than 10% of DM cases [21], while tropical DM makes up less than 1% [8]. Lifestyle factors such as sedentary lifestyle, cigarette smoking and generous consumption of alcohol are known risk factors linked to the development of T2DM. Obesity has been reported to be a major contributor to approximately 55% of diagnosed cases of T2DM, with a prevalence of 3.3 to 18% [2]. It has also been associated with several life-threatening diseases such as cardiovascular disease (CVD), several cancer types, as well as reduced quality of life [22, 23]. Diabetes-related morbidity and mortality have been reported to be high in different locations in Nigeria with 105,091 diabetes-related deaths recorded as at 2013 and most patients reported to have been suffering from T2DM [10].
2.2 Management
Given the current DM epidemic and its projected consequences, effective population-based intervention identification has become a priority public health strategy in Sub-Saharan Africa [24]. In Nigeria, insulin, oral glucose-lowering drugs, diet and exercise are used in the management of DM. Complementary and alternative medicine such as concoctions, infusions, tinctures and herbal supplement is also used [1]. Inability to use insulin syringe, the high cost of therapy, few options in the Nigerian market and poor policies on DM management are a few challenges affecting insulin treatment [25]. The medications used in the management of diabetes become less effective over time as most patients do not achieve normal glycaemic control with their use [26], and thus have resulted to possible second-line medications to achieve the normal glycaemic target [27]. Despite the high cost of medication as well as the inability to maintain normal glycaemic control for an extended period, the use of polytherapy to achieve sufficient glucose control is a common feature in Nigeria [28]. Challenges such as needle phobia, hypoglycaemia, drug-associated side effect and cost of medication have made over 46% of diabetic patients opt for complementary and alternative medicine, with Vernonia amygdalina which is also known as “bitter leaf” being most utilised [29]. The school of thought that diabetics should abstain from carbohydrate rich meals has led to the intake of monotonous food like unripe plantain, beans and wheat rich diet [1, 30]. This challenge occurs due to the absence of a taste-appealing standardised diet for diabetics as well as their dietary requirements influenced by economic status, religious and cultural beliefs [1].
3. Terminalia species as medicinal plants
Medicinal plants (MPs) are a rich source of natural products with potential medical interest. There is an increased interest in the use of medicinal plants and their products as a result of their reported wide range application. Asides their application, they are the richest bioresource of modern medicines, nutraceuticals, food supplements, chemical entities for synthetic drugs, pharmaceutical intermediates, folk medicines and drugs of traditional systems of medicine [31]. These plants are also known to contain different plant secondary metabolites such as tannins, flavonoids, saponins alkaloids, terpenoids and phenols, which are responsible for numerous characteristics such as colour, flavour, smell and texture in various parts of these plants. These plant metabolites are also known for their pharmacological mechanism of actions in the treatment, management and prevention of diseases [32].
Terminalia genus has about 250 flowering tree species which belong to the Combretaceae family. They are found in the tropics of Australia, Asia, Africa and South America. The bark of many Terminalia species appear to be cracked from the stem, the branches are arranged in a stepwise manner with the leaves appearing large and leathery on the tips of shoots. The appearance of the leaves is responsible for the genus nomenclature Terminalia which is a derivative of the Latin word Terminus. The fruits of most Terminalia species are edible with deep red, yellow or black pulp colouration and hard nuts [33]. Extensive research has shown that Terminalia species are a rich source of phytocompounds ranging from flavonoids (gallic acid, ellagic acid, quercetin, hesperetin), steroids (β-sitosterol, terminic acid), tannins (punicallin, terchebulin, castalagin), vitamins (α-tocopherol), carotenoids (lutein) and others [33, 34, 35]. The various reported pharmacological activities such as antimalarial, antioxidant, antibacterial, antifungal, cardiovascular effects, antidiarrhoeal, analgesic, anti-inflammatory, hypolipidaemic, hypoglycaemic, antiprotozoal, antiviral, wound healing, antimutagenic and anticancer properties have been attributed to these compounds [33].
3.1 Terminalia species in Nigeria
There are about ten species of Terminalia found in Nigeria, namely; Terminalia altissima (Synonym: superba), Terminalia avicennioides, Terminalia brownii, Terminalia catappa, Terminalia glaucescens, Terminalia ivorensis, Terminalia laxiflora, Terminalia macroptera, Terminalia mollis and Terminalia schimperiana [33, 36, 37]. These species have been reported to be pharmacologically active with antimicrobial, antimycobacterial, wound healing, gastroprotective, antimalarial, antioxidant, antifungal, anthelmintic, antibacterial, antifungal, antiviral, analgesic, radical scavenging, hepatoprotective, anticancer, antimutagenic, antiaging, aldose inhibitory, antiplasmodial, cytotoxic, antipsychotic, sedative, analgesic, anti-inflammatory, trypanocidal, hypolipidaemic, antioxidant, antimycoplasmal and androgenic, properties as shown in Table 1 [34, 35, 38, 39, 40, 41, 42].
Name of specie
Location in Africa
Common name
Pharmacological activity
References
Terminalia altissima (Synonym: superba)
Tropical west Africa, Sierra Leone, Congo, Nigeria, Cameroon
List of Terminalia species found in Nigeria and their reported ethnopharmacological activity.
Terminalia species in Nigeria, have numerous application in the treatment and management of ailments among the various traditional medicine systems of different ethnic groups. Different parts are utilised by traditional healers to treat cholera, malaria, typhoid, hepatitis, stomach ache, tuberculosis, leprosy, diarrhoea, skin diseases, gastritis, hyperglycaemia, diabetes, gonorrhoea, wounds, epilepsy and catarrh [56, 57, 58]. They are also used as tonic, laxative and chewing sticks [26, 59, 60].
Several reports have highlighted some pharmacological properties of Terminalia species in Nigeria, such as its antimicrobial properties, antibacterial property, anti-inflammatory action, anti-HIV, hypoglycaemic, modulatory properties, analgesic, wound healing, antioxidant and radical scavenging activity, hepatoprotective, anticancer, anti-trypanocidal, antimutagenic and antiaging properties.
Nigeria’s vegetation is made up of forests, savannahs and montane land. All others but the latter are further divided into three parts which have ensured the wide distribution of these species across the country. This variation in the country’s vegetation has not only made these Terminalia species specific to Nigeria and West Africa, but accounts for the difference in their evolutionary relationship, development and pharmacologic activity. Upon assessment of the phylogenetic relationship on www.phylogeny.fr [61], using the available nucleic acid sequence of the Terminalia species that were deposited in National Center for Biotechnology Information (NCBI) GenBank, it was observed that species that were closely related such as T. catappa and T. glaucescens as well as T. superba and T. avicennioides were located in the same vegetative region of the country (Figure 1). Irrespective of their evolutionary differences, it was observed that there were conserved regions that were similar in the deposited genetic sequence of the Terminalia species in Nigeria showing over 94% sequence similarity (Figure 2).
Figure 1.
Phylogenetic tree of some selected Terminalia species in Nigeria.
Figure 2.
Multiple sequence alignment of some selected Terminalia species in Nigeria.
3.2 Pharmacologic antidiabetic activities of Nigerian Terminalia species
The pharmacologic antidiabetic activity of Terminalia species have been reported in different climes using various in vitro, in vivo and in silico techniques in mice, rat, rabbit and humans to elucidate them. Nonetheless, in Nigeria, there is a paucity of data on the antidiabetic mode of action and mechanisms of Terminalia spp. despite its abundance. However, there are antidiabetic reports of these species from neighbouring countries with similar vegetation.
3.2.1 In vitro assessments
The crude aqueous and hydroethanolic leaf extracts of T. catappa from Nigeria have been reported to inhibit both α-glucosidase and α-amylase effectively. Mixed and non-competitive mode of inhibition were the mechanisms of action elucidated for the extracts [35]. This finding was further corroborated by in silico studies, in which the identified bioactives showed preferential binding to the active site than the allosteric site of α-glucosidase and α-amylase [35]. The α-amylase inhibitory property of crude methanol extract and solvent fractions of T. brownii stem bark was lower than that of acarbose as reported in [62]. When compared with some other medicinal plants, crude ethanol, aqueous and hydroethanolic extracts of T. superba root exhibited better inhibitory action on α-amylase activity than their respective counterparts [63]. For α-glucosidase and lipoxygenase inhibitory activity, the potency of dichloromethane, methanol and solvent fractions of T. macroptera leaves have been established to be more potent than acarbose and quercetin respectively [40].
High-throughput techniques were used to identify isolated bioactive compounds (gallic acid and methyl gallate) from T. superba stem bark dichloromethane extract, which exhibited very high inhibitory property on α-glucosidase activity [64]. Other isolates such as arjunic acid and glaucinoic acid from T. glaucescens stem barks and chebulagic acid, corilagin and narcissin from T. macroptera leaves are reported to exhibit significant β-glucuronidase, α-glucosidase and 15-lipoxygenase inhibitory activity respectively [40, 65].
3.2.2 In vivo assessments
The pre-administration of methanol-methylene chloride extract of T. glaucescens leaves have been reported to confer protective properties in mice against streptozotocin-induced diabetes effects [66]. T. schimperiana root bark extracts have been reported to be effective in reducing blood glucose and excess body lipids in alloxan-induced diabetic rats [67, 68]. The hypoglycaemic activity of T. catappa leaves has also been recorded [69]. The leaves have also been associated with a significant decrease of C-reactive protein, interleukin-6, fibrinogen and inflammatory markers associated with diabetes in rats when compared with other non-steroidal anti-inflammatory drugs [70]. In male rats fed with T. catappa drupe and seeds supplemented-diets for fourteen days, they were found to have exhibited enhanced sexual behaviour and biomarkers relevant to erectile dysfunction that were initially suppressed by streptozotocin-induced diabetic state [71]. Most research on the antidiabetic assessment of Terminalia species in Nigeria have reported the beneficial effect in rats and mice. Interestingly, in Ref. [72], T. catappa intake was found to illicit negative herb-drug effect by increasing the activity of transaminases concomitantly enhancing the adverse hepatic effects of antidiabetic drugs such as pioglitazone and atorvastatin.
4. Conclusion
The Nigerian Terminalia genus is made up of species that possess antidiabetic principles. This activity has been related to the presence and synergistic action of phytochemicals such as tannins, phenolics, terpenoids, flavonoids and other active bioconstituents. The species of this genus in Nigeria can provide great medicinal value to the country and its populace. However, most of the antidiabetic pharmacological assessment has been done only on Terminalia catappa, Terminalia glaucescens and Terminalia schimperiana. Moreso, high throughput analytical techniques and equipment can be utilised to identify and isolate novel phytocompounds that may be of therapeutic value in the management and treatment of diabetes. It is also imperative to identify the sequence of all Nigerian Terminalia species to understand better the genetic relationship, genetic variability, intraspecific variability and traits heritability in vegetative and floral characters of these species.
It was also observed that the majority of antidiabetic assessments of these Terminalia species were done in vitro, in rats and mice. Nonetheless, more in vivo studies should be carried out to identify the molecular mechanisms involved in its antidiabetic activity. Nigeria is the most challenged sub-Saharan nation with diabetes, a public health issue that needs to be tackled urgently. Hence, there is a need to increase translational research and explore the antidiabetic assessment of these Terminalia species directly on patients to extrapolate results that will be beneficial to the Nigerian public health system.
Acknowledgments
The authors acknowledge Olawumi Toyin Iheagwam for proofreading the manuscript.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"Terminalia species, antidiabetic, Nigeria, diabetes mellitus, mode of action, mechanism, traditional medicine",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73866.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73866.xml",downloadPdfUrl:"/chapter/pdf-download/73866",previewPdfUrl:"/chapter/pdf-preview/73866",totalDownloads:47,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 15th 2020",dateReviewed:"October 13th 2020",datePrePublished:"December 11th 2020",datePublished:null,dateFinished:"November 2nd 2020",readingETA:"0",abstract:"Terminalia species are well recognised in traditional medicine. They are known for producing fruits and nuts which are edible and possess pharmacotherapeutic properties. They also have ornamental purposes in urban areas where they are found. These species are used by traditional healers in the treatment and management of diabetes mellitus, its complications and other related ailments that are involved in the pathophysiological process of this disease. Research has been extensively done to validate these antidiabetic claims scientifically as well as understand the mechanism and mode of antidiabetic action. This chapter proposes to highlight the antidiabetic activities of Terminalia species found in Nigeria.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73866",risUrl:"/chapter/ris/73866",signatures:"Franklyn Nonso Iheagwam, Omoremime Elizabeth Dania, Happiness Chijioke Michael-Onuoha, Olubanke Olujoke Ogunlana and Shalom Nwodo Chinedu",book:{id:"9445",title:"Alternative Medicine",subtitle:null,fullTitle:"Alternative Medicine",slug:null,publishedDate:null,bookSignature:"Dr. Muhammad Akram",coverURL:"https://cdn.intechopen.com/books/images_new/9445.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"215436",title:"Dr.",name:"Muhammad",middleName:null,surname:"Akram",slug:"muhammad-akram",fullName:"Muhammad Akram"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Risk factors",level:"2"},{id:"sec_3",title:"2. Diabetes mellitus in Nigeria",level:"1"},{id:"sec_3_2",title:"2.1 Epidemiology",level:"2"},{id:"sec_4_2",title:"2.2 Management",level:"2"},{id:"sec_6",title:"3. Terminalia species as medicinal plants",level:"1"},{id:"sec_6_2",title:"3.1 Terminalia species in Nigeria",level:"2"},{id:"sec_7_2",title:"3.2 Pharmacologic antidiabetic activities of Nigerian Terminalia species",level:"2"},{id:"sec_7_3",title:"3.2.1 In vitro assessments",level:"3"},{id:"sec_8_3",title:"3.2.2 In vivo assessments",level:"3"},{id:"sec_11",title:"4. Conclusion",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"},{id:"sec_15",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Ogbera AO, Ekpebegh C. Diabetes mellitus in Nigeria: The past, present and future. World Journal of Diabetes. 2014;5(6):905-911'},{id:"B2",body:'Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: A review of current trends. 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Nucleic Acids Research. 2008;36(W465-W469)'},{id:"B62",body:'Alema NM, Periasamy G, Sibhat GG, Tekulu GH, Hiben MG. Antidiabetic activity of extracts of Terminalia brownii Fresen. Stem bark in mice. Journal of Experimental Pharmacology. 2020;12:61-71'},{id:"B63",body:'Momo CEN, Ngwa AF, Dongmo GIF, Oben JE. Antioxidant properties and α-amylase inhibition of Terminalia superba, Albizia sp., Cola nitida, Cola odorata and Harungana madagascarensis used in the management of diabetes in Cameroon. Journal of Health Science. 2009;55(5):732-738'},{id:"B64",body:'Wansi JD, Lallemand MC, Chiozem DD, Toze FAA, Mbaze LMA, Naharkhan S, et al. α-Glucosidase inhibitory constituents from stem bark of Terminalia superba (Combretaceae). Phytochemistry. 2007;68(15):2096-2100'},{id:"B65",body:'Rahman AU, Zareen S, Choudhary MI, Akhtar MN, Ngounou FN. Some chemical constituents of Terminalia glaucescens and their enzymes inhibition activity. Zeitschrift für Naturforschung B. 2005;60(3):347-350'},{id:"B66",body:'Njomen GB, Kamgang R, Soua PR, Oyono JL, Njikam N. Protective effect of methanol-methylene chloride extract of Terminalia glaucescens leaves on streptozotocin-induced diabetes in mice. Tropical Journal of Pharmaceutical Research. 2009;8(1):19-26'},{id:"B67",body:'Khan M, Bala L, Igoli J. Isolation of caccigenin and investigation of anti-diabetic properties of tropical almond (Terminalia schimperiana) root bark extracts on albino rats. Journal of Chemical Society of Nigeria. 2019;44(3)'},{id:"B68",body:'Ojewumi A, Kadiri M. Phytochemical screening and anti-diabetic properties of Terminalia schimperiana leaves on rats. International Journal of Green and Herbal Chemistry. 2014;3(4):1679-1689'},{id:"B69",body:'Koffi NG, Yvetten FN, Noel ZG. Effect of aqueous extract of Terminalia catappa leaves on the glycaemia of rabbits. Journal of Applied Pharmaceutical Science. 2011;1(8):59-64'},{id:"B70",body:'Ben EE, Asuquo AE, Owu DU. Comparative effect of aspirin, meloxicam and Terminalia catappa leaf extract on serum levels of some inflammatory markers in alloxan induced diabetic rats. Asian Journal of Research in Biochemistry. 2019;4(1):1-10'},{id:"B71",body:'Adebayo AA, Oboh G, Ademosun AO. Almond-supplemented diet improves sexual functions beyond Phosphodiesterase-5 inhibition in diabetic male rats. Heliyon. 2019;5(12):e03035'},{id:"B72",body:'Ezuruike U, Prieto JM. Assessment of potential herb-drug interactions among Nigerian adults with type-2 diabetes. Frontiers in Pharmacology. 2016;7:248'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Franklyn Nonso Iheagwam",address:"franklyn.iheagwam@covenantuniversity.edu.ng",affiliation:'
Department of Biochemistry and Covenant University Public Health and Wellness Research Cluster (CUPHWERC), Covenant University, Nigeria
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Department of Biochemistry and Covenant University Public Health and Wellness Research Cluster (CUPHWERC), Covenant University, Nigeria
Department of Biochemistry and Covenant University Public Health and Wellness Research Cluster (CUPHWERC), Covenant University, Nigeria
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Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
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In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
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Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at oapf@intechopen.com
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Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at oapf@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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