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Search Results (38)

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20 pages, 504 KiB  
Systematic Review
Manifestations and Treatment of Hypovitaminosis in Oral Diseases: A Systematic Review
by Barbara Bačun, Dora Galić, Luka Pul, Matej Tomas and Davor Kuiš
Dent. J. 2024, 12(6), 152; https://doi.org/10.3390/dj12060152 - 21 May 2024
Viewed by 1344
Abstract
This review’s objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in [...] Read more.
This review’s objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in this review had to be published in English between 2017 and 2023, be original studies, and involve human subjects. Fifteen studies were included in this review: three examining oral symptoms of vitamin B12 deficiency; one assessing vitamin B complex and vitamin E for recurrent oral ulcers; one investigating serum vitamin D levels in recurrent aphthous stomatitis patients; three exploring hypovitaminosis effects on dental caries; two measuring blood serum vitamin D levels; one evaluating vitamin B12 hypovitaminosis; three investigating hypovitaminosis as indicative of gingival disease; one focusing on vitamin deficiencies and enamel developmental abnormalities; one assessing vitamin deficiencies in oral cancer patients; one examining vitamin K as an oral anticoagulant and its role in perioperative hemorrhage; and one evaluating vitamin effects on burning mouth syndrome. Despite some limitations, evidence suggests a correlation between vitamin deficiencies and oral symptoms. This systematic review was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (202430039). Full article
(This article belongs to the Special Issue Molecular Diagnostics in Oral Diseases: Volume II)
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<p>Prisma flowchart of search results.</p>
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20 pages, 875 KiB  
Systematic Review
Efficacy and Safety of Propolis for Treating Recurrent Aphthous Stomatitis (RAS): A Systematic Review and Meta-Analysis
by Tina Roberts, Idriss Ibrahim Kallon and Anel Schoonees
Dent. J. 2024, 12(1), 13; https://doi.org/10.3390/dj12010013 - 6 Jan 2024
Cited by 1 | Viewed by 2453
Abstract
The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no [...] Read more.
The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall ‘high risk’ of bias, while the remaining studies were categorised as having an overall ‘uncertain risk’. The overall certainty of the evidence was ‘very low’. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS. Full article
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<p>PRISMA flow chart.</p>
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<p>Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.</p>
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13 pages, 3372 KiB  
Article
A Thermally Stable Recombinant Human Fibronectin Peptide-Fused Protein (rhFN3C) for Faster Aphthous Ulcer (AU) Healing
by Xiang Cai, Jiawen Zhu, Xin Luo, Guoguo Jin, Yadong Huang and Lihua Li
Bioengineering 2024, 11(1), 38; https://doi.org/10.3390/bioengineering11010038 - 29 Dec 2023
Viewed by 1532
Abstract
Approximately 59.4–100% of head and neck cancer patients receiving radiotherapy or radio chemotherapy suffer from aphthous ulcers (AUs), which seriously affect the subsequent treatment. At the same time, AUs are a common oral mucosal disease with a high incidence rate among the population, [...] Read more.
Approximately 59.4–100% of head and neck cancer patients receiving radiotherapy or radio chemotherapy suffer from aphthous ulcers (AUs), which seriously affect the subsequent treatment. At the same time, AUs are a common oral mucosal disease with a high incidence rate among the population, often accompanied by severe pain, and affect both physical and mental health. Strategies to increase the ulcer healing rate and relieve pain symptoms quickly is a long-term clinical objective. Oral mucosal discontinuity is the main histological hallmark of AUs. So, covering the inner mucosal defect with an in vitro engineered oral mucosal equivalent shows good prospects for AU alleviation. Fibronectin (FN) is a glycopeptide in the extracellular matrix and exhibits opsonic properties, aiding the phagocytosis and clearance of foreign pathogens through all stages of ulcer healing. But native FN comes from animal blood, which has potential health risks. rhFN3C was designed with multi-domains of native FN, whose core functions are the recruitment of cells and growth factors to accelerate AU healing. rhFN3C is a peptide-fused recombinant protein. The peptides are derived from the positions of 1444–1545 (FNIII10) and 1632–1901 (FNIII12–14) in human native FN. We optimized the fermentation conditions of rhFN3C in E. coli BL21 to enable high expression levels. rhFN3C is thermally stable and nontoxic for L929, strongly promotes the migration and adhesion of HaCaT, decreases the incidence of wound infection, and shortens the mean healing time by about 2 days compared to others (p < 0.01). rhFN3C may have great potential for use in the treatment of AUs. The specific methods and mechanisms of rhFN3C are yet to be investigated. Full article
(This article belongs to the Special Issue Biologically Active Recombinant Proteins)
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<p>Construction and expression of rhFN3C. (<b>A</b>) Recombinant plasmid map of pET20b-rhFN3C. (<b>B</b>) SDS-PAGE analysis of the expression level of rhFN3C in different expression strains. M: protein marker. Lanes 1–4: induced cells. Lane 5: uninduced cells. (<b>C</b>) SDS-PAGE analysis of the effects of different temperatures, induction times, and IPTG concentrations on protein expression. M: protein marker. B: uninduced. Lanes 1–3: 0.25, 0.5, and 1.0 mM IPTG, respectively. (<b>D</b>) WB identification of recombinant protein rhFN3C. M: protein marker. (<b>E</b>) Screening and optimization of the rhFN3C purification process. S: cell lysate. P: cell pellet. M: protein marker. Lanes 1–3: flow-through, wash, and elution, respectively. (<b>F</b>) SDS-PAGE analysis of protein purity in the eluate from G25 gel filtration chromatography. M: protein marker. Lanes 1–3: elution solutions collected at different times. (<b>G</b>) HPLC analysis of protein purity of rhFN3C. Red arrows (<b>A</b>–<b>F</b>): Destination bands for rhFN3C. Red arrow (<b>G</b>): The characteristic peaks of rhFN3C.</p>
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<p>The line chart of remaining percentage comparisons of rhFN3C and BSA.</p>
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<p>Performance comparison of rhFN3C with FN10 and FN12–14. (<b>A</b>) The MTT method detects the proliferative effects of various concentrations of rhFN3C on L929 cells after 24 h, 48 h, and 72 h of culture. Note: n = 3, ns = No Significant. (<b>B</b>) The migration and healing rate of HaCaT cells induced by rhFN3C. Note: n = 3; *, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***; and <span class="html-italic">p</span> &lt; 0.001 (scale bar = 200 μm). (<b>C</b>) Detection of the adhesive effect of rhFN3C on HaCaT and BALB/c 3T3 cells. Note: n = 3; *, <span class="html-italic">p</span> &lt; 0.05; ***, <span class="html-italic">p</span> &lt; 0.001; ****, and <span class="html-italic">p</span> &lt; 0.0001 (scale bar = 100 μm).</p>
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<p>Experimental study on the healing of aphthous ulcers in rats treated with different concentrations of rhFN3C. (<b>A</b>) Schematic illustration of the experimental procedure. (<b>B</b>) Condition of the wound in rats with aphthous ulcers on days 1, 3, 5, 7, and 9 (scale bar = 0.5 mm). Note: The black circle = Unhealed areas. (<b>C</b>) The healing rate of the wound in rats with aphthous ulcers. n = 6, means ± SD.</p>
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<p>Histological observations. (<b>A</b>) Transmission light of H&amp;E-stained images of defect sites treated with rhFN3C on Day 9 after surgery (40×: scale bar = 200 μm; 200×: scale bar = 100 μm). (<b>B</b>) Transmitted light pictures of the Masson’s trichrome-stained parts of the defects treated with rhFN3C at 9 days post-surgery, indicating collagen deposition (40×: scale bar = 200 μm; 200×: scale bar = 100 μm).</p>
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11 pages, 1182 KiB  
Hypothesis
A New Hypothesis Describing the Pathogenesis of Oral Mucosal Injury Associated with the Mammalian Target of Rapamycin (mTOR) Inhibitors
by Stephen T. Sonis and Alessandro Villa
Cancers 2024, 16(1), 68; https://doi.org/10.3390/cancers16010068 - 22 Dec 2023
Viewed by 1709
Abstract
It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so [...] Read more.
It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from those of other anti-cancer agents, occur with regularity, and impact patient outcomes. mIAS’ pathogenesis has been the subject of speculation, and its similar presentation to recurrent aphthous stomatitis (RAS) has led to the hypothesis that it might serve as a surrogate to better understand RAS. Based on a review of the literature, the current manuscript provides a hypothesis regarding the mechanisms by which mTORis uniquely initiate mucosal injury and an explanation for the observation that steroids (also an immunosuppressive) are effective in its treatment through a non-immunologic mechanism. Unexplained unique features of mIAS are discussed in this review in the context of future investigation. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Treatment Resistance)
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<p>Similarity in clinical presentation of mIAS ((<b>right</b>) panel) and recurrent aphthous stomatitis ((<b>left</b>) panel).</p>
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<p>Levels of IL-6 in organotypic human oral mucosal tissue treated with everolimus without or with TFF 1. IL-6 was measured in supernatants from oral mucosal tissue collected 24 h after everolimus stimulation. Supernatants were analyzed for levels of human IL-6 using a MagPix multiplex analyzer. Data are graphed as Mean ± SEM for each group (n = 4) and data were analyzed via One-way ANOVA and Dunnett’s multiple comparison’s test, * <span class="html-italic">p</span> &lt; 0.05 compared to Everolimus (+) Control group. From Sonis S, Andreotta PW, Lyng G. On the pathogenesis of mTOR inhibitor-associated stomatitis (mIAS)—studies using an organotypic model of the oral mucosa. Oral Dis 2017; 23:247–52 [<a href="#B19-cancers-16-00068" class="html-bibr">19</a>].</p>
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<p>Quantification of PCNA and TUNEL staining in an organotypic model of human oral mucosal tissues. PCNA staining was used to assess cell proliferation. Data are expressed as an average number of PCNA–positive cells across four fields at 20× magnification, averaged per group; data graphed are mean ± SEM per group where n = 3. Data were analyzed via one-way ANOVA and Dunnett’s multiple comparisons. ***: <span class="html-italic">p</span> ≤ 0.005 compared to Everolimus (+) group. TUNEL staining was used to assess apoptotic cells and data are expressed as an average number of TUNEL-positive cells across four fields at 40× magnification, averaged per group; data graphed are mean ± SEM per group where n = 3. Data were analyzed via one-way ANOVA and Dunnett’s multiple comparisons. * <span class="html-italic">p</span> &lt; 0.05 compared to Everolimus (+) group. From Sonis S, Andreotta PW, Lyng G. On the pathogenesis of mTOR inhibitor-associated stomatitis (mIAS)—studies using an organotypic model of the oral mucosa. Oral Dis 2017; 23:247–52 [<a href="#B19-cancers-16-00068" class="html-bibr">19</a>].</p>
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46 pages, 1743 KiB  
Review
Medicinal Plants for Dermatological Diseases: Ethnopharmacological Significance of Botanicals from West Africa in Skin Care
by Mokgadi Ursula Makgobole, Nomakhosi Mpofana and Abdulwakeel Ayokun-nun Ajao
Cosmetics 2023, 10(6), 167; https://doi.org/10.3390/cosmetics10060167 - 7 Dec 2023
Cited by 2 | Viewed by 4783
Abstract
Skin disease is a severe health issue that affects a lot of people in Africa and is vastly underreported. Because of their availability, affordability, and safety, medicinal plants represent a major source of treatment for various skin diseases in West Africa. This review [...] Read more.
Skin disease is a severe health issue that affects a lot of people in Africa and is vastly underreported. Because of their availability, affordability, and safety, medicinal plants represent a major source of treatment for various skin diseases in West Africa. This review presents the medicinal plants used in treating skin diseases in West Africa and their available biological activities that have lent credence to their skin care usage. A total of 211 plant species from 56 families are implicated to be used in West Africa for several skin conditions such as aphthous ulcers, burns, eczema, scabies, sores, and wounds. Fabaceae is the most-implicated family (30 species) for the treatment of skin diseases, followed by Combretaceae (14 species) and Asteraceae (13 species). Most of the medicinal plants used are trees (93); leaves (107) were the most-used plant part, and decoction (73) was the preferred preparation method for the medicinal plants. The biological activities related to the pathology of skin diseases, such as antimicrobial and anti-inflammatory properties of 82 plants, have been evaluated. Based on their minimum inhibitory concentration, the most active antimicrobial plant is Brillantaisia lamium. Among the isolated phytochemicals, betulenic acid and lespedin were the most active, while plants such as Kigelia africana and Strophanthus hispidus showed significant wound-healing activities. This review highlights research gaps in the ethnobotanical studies of many West African countries, the biological activities of plants used to treat skin diseases, and the cosmetic potential of these plants. Full article
(This article belongs to the Special Issue Application of Plant-Based Molecules and Materials in Cosmetics)
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<p>PRISMA flow chart showing total studies identified, removed, excluded, and included in the review.</p>
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<p>Most cited plant families.</p>
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<p>Life forms of the reported plants.</p>
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<p>Parts of plants used to make herbal remedies.</p>
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<p>Mode of preparation.</p>
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<p>Number of plants used in treating different skin diseases.</p>
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19 pages, 1009 KiB  
Review
Otorhinolaryngological Manifestations and Esophageal Disorders in Celiac Disease: A Narrative Review
by Herbert Wieser, Carolina Ciacci, Carolina Gizzi and Antonella Santonicola
J. Clin. Med. 2023, 12(22), 7036; https://doi.org/10.3390/jcm12227036 - 10 Nov 2023
Cited by 2 | Viewed by 1421
Abstract
Celiac disease (CeD) is a chronic gluten-sensitive immune-mediated enteropathy characterized by numerous intestinal and extra-intestinal signs and symptoms. Among extra-intestinal manifestations, otorhinolaryngological (ORL) complaints in CeD are relatively rare and their relation to CeD is frequently overlooked by physicians. Recent studies underlined that [...] Read more.
Celiac disease (CeD) is a chronic gluten-sensitive immune-mediated enteropathy characterized by numerous intestinal and extra-intestinal signs and symptoms. Among extra-intestinal manifestations, otorhinolaryngological (ORL) complaints in CeD are relatively rare and their relation to CeD is frequently overlooked by physicians. Recent studies underlined that the prevalence of recurrent aphthous stomatitis, aphthous ulcers, geographic tongue, and xerostomia was significantly increased in CeD patients compared with healthy individuals. However, data about the other oral manifestations of CeD, such as atrophic glossitis, glossodynia, angular cheilitis, and salivary abnormalities, are scanty. Further ORL conditions associated with CeD include sensorineural hearing loss, nasal abnormalities, and obstructive sleep apnea. Moreover, several esophageal disorders such as gastroesophageal reflux disease and eosinophilic esophagitis have been associated with CeD. The pathophysiological link between both ORL and esophageal manifestations and CeD might be further investigated. In addition, also the role of gluten-free diet in improving these conditions is largely unclear. Certainly, otorhinolaryngologists can play an important role in identifying people with unrecognized CeD and may help prevent its long-term complications. The aim of this narrative review is to analyze the latest evidence on the association between CeD and ORL and esophageal manifestations. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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<p>PRISMA flow diagram of search procedure.</p>
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<p>An aphthous ulcer in the oral cavity.</p>
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<p>Some of the endoscopic findings of EoE: longitudinal furrows, white exudates (<b>A</b>); esophageal rings (<b>B</b>).</p>
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16 pages, 2568 KiB  
Review
The Power of Licorice (Radix glycyrrhizae) to Improve Oral Health: A Comprehensive Review of Its Pharmacological Properties and Clinical Implications
by Hebah AlDehlawi and Ahoud Jazzar
Healthcare 2023, 11(21), 2887; https://doi.org/10.3390/healthcare11212887 - 2 Nov 2023
Cited by 2 | Viewed by 5010
Abstract
Licorice (Radix glycyrrhizae) is a plant root extract widely used in various applications, including cosmetics, food supplements, and traditional medicine. It has a long history of medicinal use in different cultures due to its diverse pharmacological properties. Licorice has traditionally been [...] Read more.
Licorice (Radix glycyrrhizae) is a plant root extract widely used in various applications, including cosmetics, food supplements, and traditional medicine. It has a long history of medicinal use in different cultures due to its diverse pharmacological properties. Licorice has traditionally been used for treating gastrointestinal problems, respiratory infections, cough, bronchitis, arthritis, and skin conditions. In recent years, the potential therapeutic benefits of licorice for oral health have gained significant interest. This paper aims to provide a comprehensive review of the effects of licorice extracts and their bioactive components on common oral diseases such as dental caries, periodontitis, halitosis, candidiasis, and recurrent aphthous ulcers. The chemical composition of licorice has shown the presence of several bioactive compounds such as glycyrrhizin, glabridin, isoliquiritigenin (ISL), and licochalcone exhibiting various pharmacological activities, including anti-inflammatory, antimicrobial, antioxidative, and immunomodulatory effects. Interestingly, in certain patients, licorice has shown a promising potential to inhibit the spread of viruses, prevent biofilm formation, reduce inflammation, boost immune responses, alleviate pain, and exert antioxidative effects. In this review, we provide a brief overview of the current understanding of licorice’s therapeutic benefits in the treatment of oral ailments, emphasising its potential as an alternative treatment option for oral diseases. Further research is warranted to explore its efficacy, safety, and clinical applications using placebo-controlled clinical trials. Full article
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<p>Effect of licorice (<span class="html-italic">Radix glycyrrhizae</span>) on oral health.</p>
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13 pages, 3361 KiB  
Article
Measuring the Whole Wall Thickness of the Common Femoral Vein as a Distinctive Diagnostic Tool to Distinguish Behçet’s Disease Presenting with Oral Ulcers from Recurrent Aphthous Stomatitis
by Adem Erturk, Yasin Sarıkaya, Hüseyin Coşkun and Çağrı Turan
Diagnostics 2023, 13(16), 2705; https://doi.org/10.3390/diagnostics13162705 - 19 Aug 2023
Cited by 1 | Viewed by 1262
Abstract
Recurrent oral ulcers, which are the first and most common manifestation of Behçet’s disease (BD), have several etiological causes but are often idiopathic and known as recurrent aphthous stomatitis (RAS). In recent years, publications have drawn attention to the fact that whole-wall thickness [...] Read more.
Recurrent oral ulcers, which are the first and most common manifestation of Behçet’s disease (BD), have several etiological causes but are often idiopathic and known as recurrent aphthous stomatitis (RAS). In recent years, publications have drawn attention to the fact that whole-wall thickness (WWT) and intima–media thickness (IMT) measurements of the common femoral vein (CFV) may be useful in the diagnosis of BD, which are independent of organ involvement. In this study, the usefulness of the WWT and IMT of the CFV measured by venous Doppler ultrasound (US) was investigated in differentiating BD presenting with oral ulcers from RAS. Patients with BD (n = 84), patients with RAS (n = 85), and healthy controls (HCs) (n = 70) were the three groups included. Both the right and left WWT of the CFV were significantly higher in the BD compared with the HCs and RAS groups (p < 0.001). The diagnostic cutoff values of ≥0.58 mm for the WWT of the CFV performed well against both the patients with RAS and HCs for the discrimination of BD (sensitivity = 79.8%, specificity = 64.7%). In patients with recurrent oral ulcers, the WWT of the CFV measurement may be a distinctive new diagnostic tool for the differential diagnosis of BD and RAS. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Inclusion and exclusion criteria of the study.</p>
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<p>The patient inclusion and exclusion flowchart.</p>
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<p>The measurement of the common femoral vein whole-wall (1) and intima–media thickness (2) in a patient with Behçet’s Disease.</p>
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<p>Evaluation of the WWT of CFV measurement with receiver operating characteristic curve graph in the distinction of RAS and BD.</p>
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21 pages, 5668 KiB  
Article
Formulation and Evaluation of Prednisolone Sodium Metazoate-Loaded Mucoadhesive Quatsomal Gel for Local Treatment of Recurrent Aphthous Ulcers: Optimization, In Vitro, Ex Vivo, and In Vivo Studies
by Ashraf Kassem, Hanan Refai, Mohamed A. El-Nabarawi and Menna M. Abdellatif
Pharmaceutics 2023, 15(7), 1947; https://doi.org/10.3390/pharmaceutics15071947 - 14 Jul 2023
Cited by 3 | Viewed by 1850
Abstract
This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was [...] Read more.
This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was conducted to address the impact of independent variables QAS type (X1), QAS to CHO molar ratio (X2), and sonication time (X3). The dependent variables were particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3), entrapment efficiency percent (EE%; Y4) and percent of drug released after 6 h (Q6%: Y5). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases. Full article
(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)
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<p>(<b>a</b>) 3D plot for the effect of (QAS) type (A), (QAS), and (CHO) molar ratio (B) on PS, (<b>b</b>) 3D plot for the effect of (QAS) type (A) and sonication time (C) on PS. Abbreviation: QAS—quaternary ammonium surfactants; CHO—cholesterol; PS—particle size.</p>
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<p>(<b>a</b>) 3D plot for the effect of (QAS) type (A), (QAS), and (CHO) molar ratio (B) on PDI, (<b>b</b>) 3D plot for the effect of (QAS) type (A) and sonication time (C) on PDI. Abbreviation: QAS—quaternary ammonium surfactants; CHO—cholesterol; PDI—polydispersity index.</p>
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<p>(<b>a</b>) 3D plot for the effect of (QAS) type (A), (QAS), and (CHO) molar ratio (B) on ZP, (<b>b</b>) 3D plot for the effect of (QAS) type (A) and sonication time (C) on ZP. Abbreviation: QAS—quaternary ammonium surfactants; CHO—cholesterol; ZP—zeta potential.</p>
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<p>(<b>a</b>) 3D plot for the effect of (QAS) type (A), (QAS), and (CHO) molar ratio (B) on EE, (<b>b</b>) 3D plot for the effect of (QAS) type (A) and sonication time (C) on EE. Abbreviation: QAS—quaternary ammonium surfactants; CHO—cholesterol; EE—entrapment efficiency.</p>
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<p>In vitro drug release profiles from different quatsomal formulae.</p>
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<p>(<b>a</b>) 3D plot for the effect of (QAS) type (A), (QAS), and (CHO) molar ratio (B) on Q6%, (<b>b</b>) 3D plot for the effect of (QAS) type (A) and sonication time (C) on Q6%. Abbreviation: QAS—quaternary ammonium surfactants; CHO—cholesterol; Q6%—percent of drug released after 6 h.</p>
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<p>Morphology of the optimized quatsomal formula (F4).</p>
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<p>FTIR spectrum of (<b>a</b>) prednisolone sodium metazoate, (<b>b</b>) cholesterol, (<b>c</b>) lyophilized quatsomal formula, (<b>d</b>) dimethyldidodecylammonium bromide.</p>
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<p>Chemical structure of (<b>a</b>) prednisolone sodium metazoate, (<b>b</b>) dimethyldidodecylammonium bromide, and (<b>c</b>) cholesterol [<a href="#B57-pharmaceutics-15-01947" class="html-bibr">57</a>].</p>
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<p>In vitro drug release profiles from different quatsomal gel formulae.</p>
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<p>Photographs showing ulcer diameters in different groups after 4 and 8 days, GP2—positive control group, GP3—free drug gel group, GP4—quatsomal gel group; the circles in the photographs point to the site of ulceration in the buccal mucosa.</p>
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<p>Diameter of ulcers in different groups after 4 and 8 days; ns—not-significant; *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Photomicrographs represented the histopathological differences in buccal tissues among examined groups in 4 and 8 days (Hematoxylin and Eosin stain, magnification power 400×, and scale bar 200 µm and 50 µm), GP1—negative control group, GP2—positive control group, GP3—free drug gel group, GP4—quatsomal gel group.</p>
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<p>Assessment of serum interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha of different animal groups, GP1—negative control group, GP2—positive control group, GP3—free drug gel group, GP4—quatsomal gel group—ns, not significant; **** <span class="html-italic">p</span> &lt; 0.0001; *** <span class="html-italic">p</span> &lt; 0.001; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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15 pages, 692 KiB  
Article
Association of Surfactant Protein D Single Nucleotide Polymorphisms rs721917, rs2243639, rs3088308 with Recurrent Aphthous Stomatitis in Pakistani Population
by Zainab Rizvi, Nakhshab Choudhry, Aamir Jamal Gondal and Nighat Yasmin
Genes 2023, 14(5), 1119; https://doi.org/10.3390/genes14051119 - 22 May 2023
Viewed by 1736
Abstract
Recurrent aphthous stomatitis (RAS) is a benign ulcerative condition, defined by the recurrent formation of non-contagious mucosal ulcers. Surfactant protein D (SP-D) is secreted frequently at surfaces exposed directly to body fluids. This study aims to investigate the association of SP-D single nucleotide [...] Read more.
Recurrent aphthous stomatitis (RAS) is a benign ulcerative condition, defined by the recurrent formation of non-contagious mucosal ulcers. Surfactant protein D (SP-D) is secreted frequently at surfaces exposed directly to body fluids. This study aims to investigate the association of SP-D single nucleotide polymorphisms (SNPs) with the onset of RAS. Blood samples from 212 subjects (106 cases/controls each) were collected during 2019 and genotyped for SP-D SNPs (rs721917, rs2243639, rs3088308) by polymerase chain reaction and restriction fragment length polymorphism followed by 12% polyacrylamide gel electrophoresis. Minor aphthous (75.5%) was the commonly observed ulcer type as compared to herpetiform (21.7%) and major aphthous ulcers (2.8%). A family history of RAS was reported in 70% of cases. RAS was found significantly associated with rs3088308 genotypes T/A (95% (Cl): 1.57–5.03, p = 0.0005), A/A (95% (Cl): 1.8–6.7, p = 0.0002), T-allele (95% (Cl): 1.09–2.36, p = 0.01), A-allele (95% (Cl): 1.42–3.91, p = 0.01), rs721917 genotype T/T (95% (Cl): 1.15–25.35, p = 0.03), and T-allele (95% (Cl): 1.28–3.10, p = 0.002). Female gender and obese body mass index (BMI) were significantly associated with rs3088308 genotypes T/A (95% (CI): 1.89–15.7, p = 0.001), T/T (95% (Cl): 1.52–11.9, p = 0.005), A-allele (95% (Cl): 1.65–7.58, p < 0.001), and T-allele (95% (Cl): 1.4–10.1, p <0.001) and rs721917 genotype T/T (95% (CI) = 1.3–33, p = 0.02), respectively. This study describes the association of SP-D SNPs (rs721917, rs3088308) with RAS in the Pakistani population. Full article
(This article belongs to the Special Issue Molecular Genetic Mechanisms of Oral Diseases)
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<p>PAGE (12%) for detection of SP-D SNPs. L represents DNA ladder 50 bp, P represents patient number. (<bold>A</bold>) SP-D SNP rs721917, (<bold>B</bold>) SP-D SNP rs2243639, (<bold>C</bold>) SP-D SNP rs3088308.</p>
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11 pages, 1517 KiB  
Article
Healing of Recurrent Aphthous Stomatitis by Non-Thermal Plasma: Pilot Study
by Norma Guadalupe Ibáñez-Mancera, Régulo López-Callejas, Víctor Hugo Toral-Rizo, Benjamín Gonzalo Rodríguez-Méndez, Edith Lara-Carrillo, Rosendo Peña-Eguiluz, Regiane Cristina do Amaral, Antonio Mercado-Cabrera and Raúl Valencia-Alvarado
Biomedicines 2023, 11(1), 167; https://doi.org/10.3390/biomedicines11010167 - 9 Jan 2023
Cited by 6 | Viewed by 2281
Abstract
Recurrent aphthous stomatitis (RAS) is a common disease in the oral cavity characterized by recurrent ulcers (RU). Usually, these cause acute pain without definitive treatment. The present study determines the efficacy of non-thermal plasma (NTP) for treating RU. NTP is applied to the [...] Read more.
Recurrent aphthous stomatitis (RAS) is a common disease in the oral cavity characterized by recurrent ulcers (RU). Usually, these cause acute pain without definitive treatment. The present study determines the efficacy of non-thermal plasma (NTP) for treating RU. NTP is applied to the patient’s RU using a radiofrequency generator connected to a point reactor. The power density applied to the ulcer is 0.50 W/cm2, less than 4 W/cm2, which is the maximum value without biological risk. Each patient received two treatments of three minutes each and spaced 60 min apart at a distance of 5 mm from the RU. From a sample of 30 ulcers in patients treated for RU with an average age of 37 years, they stated that the pain decreased considerably and without the need for ingestion of analgesics and antibiotics. Regeneration took place in an average of three days. The NTP proved to be an excellent therapeutic alternative for the treatment of RU since it has a rapid effect of reducing pain and inflammation, as well as adequate tissue regeneration. Full article
(This article belongs to the Special Issue Plasma Applications in Biomedicine)
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<p>Clinical characteristics of: (<b>A</b>) minor RAS, (<b>B</b>) major RAS, (<b>C</b>) herpetiform RAS.</p>
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<p>Plasma reactor and non-thermal plasma application in the patient.</p>
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<p>RU in the buccal mucosa, horizontally showing the evolution of the ulcers in three patients; (<b>a</b>,<b>d</b>,<b>g</b>) correspond to the initial state of the RU; (<b>b</b>,<b>e</b>,<b>h</b>) show regeneration after the first application of NTP; finally, (<b>c</b>,<b>f</b>,<b>i</b>) show the healthy tissue 24 h after starting the treatment.</p>
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<p>RU is located in different parts of the oral cavity (indicated with arrows): (<b>a</b>,<b>d</b>,<b>g</b>) at patient admission. (<b>b</b>,<b>e</b>,<b>h</b>) after the first application of the NTP. Finally, (<b>c</b>,<b>f</b>,<b>i</b>) show follow-up when the wound has healed (indicated with arrows).</p>
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10 pages, 945 KiB  
Article
Analysis of the Risk of Oral Squamous Cell Carcinoma in Patients with and without Recurrent Aphthous Stomatitis: A Retrospective Evaluation of Real-World Data of about 150,000 Patients
by Moritz Hertel, Senem Birinci, Max Heiland, Robert Preissner, Susanne Nahles, Andrea-Maria Schmidt-Westhausen and Saskia Preissner
Cancers 2022, 14(23), 6011; https://doi.org/10.3390/cancers14236011 - 6 Dec 2022
Cited by 2 | Viewed by 2029
Abstract
Background: Recurrent aphthous stomatitis (RAS) is found among the most frequent diseases of the oral cavity. It is characterized by repeated formation of painful ulcers. The question has risen if due to potential tumor-promoting inflammation and sustaining proliferative signaling RAS may contribute to [...] Read more.
Background: Recurrent aphthous stomatitis (RAS) is found among the most frequent diseases of the oral cavity. It is characterized by repeated formation of painful ulcers. The question has risen if due to potential tumor-promoting inflammation and sustaining proliferative signaling RAS may contribute to oral cancer. Accordingly, the aim of the study was to assess if an association of RAS and the development oral squamous cell carcinoma (OSCC) could be found in a larger cohort. As recurrent aphthous stomatitis is not classified as an oral potentially malignant disorder, it was assumed that the risk of OSCC did not differ between patients with (cohort I) and without RAS (cohort II). Methods: Retrospective clinical data of patients diagnosed with and without RAS (International Classification of Diseases (ICD)-10 code K12) within the past 20 years and a body mass index of 19–30 kg/m2 were retrieved from the TriNetX database to gain initial cohort 0. Subjects suffering from RAS were assigned to cohort I, whereby cohort II was obtained from the remaining individuals, and by matching for age, gender, as well as (history of) nicotine and alcohol dependence. After defining the primary outcome as “OSCC” (ICD-10 codes C00-C14), a Kaplan–Meier analysis was performed, and risk and odds ratios were calculated. Results: Of a total of 24,550,479 individuals in cohort 0, 72,845 subjects were each assigned to cohort I (females: 44,031 (60.44%); males: 28,814 (39.56%); mean current age (±standard deviation) = 35.51 ± 23.55 years) and II (females: 44,032 (60.45%); males: 28,813 (39.55%); mean current age (±standard deviation) = 35.51 ± 23.56 years). Among the cohorts I and II, 470 and 135 patients were diagnosed with OSCC within five years. The according risk of developing oral cancer was 0.65% and 0.18%, whereby the risk difference of 0.47% was highly significant (p < 0.0001; Log-Rank test). The RR and OR were calculated as 3.48 (95% confidence interval (CI) lower: 2.88 and upper: 4.21) and 3.50 (95% CI lower: 2.89 and upper: 4.24). Conclusions: Among the patients suffering from RAS, a significantly augmented risk of developing OSCC was found. However, it has to be emphasized that the recent literature does not provide any confirmatory evidence that supports the retrieved results. Furthermore, the findings need to be interpreted cautiously due to specific limitations that come along with the applied methods. It should thus far only be concluded that further research is necessary to evaluate hypotheses that may be retrieved from the obtained results. Despite this controversy, oral ulcers suspicious of OSCC should undergo biopsy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary. Full article
(This article belongs to the Special Issue Bioinformatics in Cancer Diagnostics and Screening)
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<p>Modified CONSORT flow chart. Note: the number of eligible subjects was ≥40,000,000, which is above the analysis capacity of TriNetX. As a consequence, additional inclusion criteria were necessary to restrict the enclosure of patients.</p>
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<p>Number of patients with and without recurrent aphthous stomatitis (RAS; ICD-10 code K12), and risk of oral squamous cell carcinoma.</p>
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<p>Kaplan–Meier diagram of the cohorts I (patients with recurrent aphthous stomatitis (RAS; ICD-10 code K12) and II (subjects without RAS). cohort I = purple; cohort II = green.</p>
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12 pages, 751 KiB  
Review
Oral Mucosal Lesions in Childhood
by Lorena Horvat Aleksijević, Jelena Prpić, Miranda Muhvić Urek, Sonja Pezelj-Ribarić, Nataša Ivančić-Jokić, Romana Peršić Bukmir, Marko Aleksijević and Irena Glažar
Dent. J. 2022, 10(11), 214; https://doi.org/10.3390/dj10110214 - 9 Nov 2022
Cited by 5 | Viewed by 8347
Abstract
Childhood diseases are a continuous source of interest in all areas of general and dental medicine. Congenital, developmental, and hereditary diseases may either be present upon birth or appear in early childhood. Developmental anomalies, although often asymptomatic, may become grounds for different infections. [...] Read more.
Childhood diseases are a continuous source of interest in all areas of general and dental medicine. Congenital, developmental, and hereditary diseases may either be present upon birth or appear in early childhood. Developmental anomalies, although often asymptomatic, may become grounds for different infections. Furthermore, they can indicate certain systemic disorders. Childhood age frequently brings about benign tumors and different types of traumatic lesions to the oral mucosa. Traumatic lesions can be caused by chemical, mechanical, or thermal injury. Mucocele and ranula are, by definition, traumatic injuries of the salivary glands or their ducts. Recurrent aphthous lesions are the most common type of ulcerations in childhood, and their etiology is considered multifactorial. Oral mucosal lesions in children require different treatment approaches depending on etiological factors and clinical presentation. Clinicians should have adequate knowledge of oral anatomy in order to diagnose and treat pathological conditions. Full article
(This article belongs to the Special Issue Dentistry Journal: 10th Anniversary)
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<p>Geographic tongue.</p>
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<p>Aphtae minor.</p>
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1 pages, 185 KiB  
Abstract
Development of In Situ Gel Containing Phytoconstituents for the Treatment of Mouth Ulcers
by Kevinkumar Garala and Parag Rabara
Med. Sci. Forum 2022, 14(1), 135; https://doi.org/10.3390/ECMC2022-13438 - 1 Nov 2022
Viewed by 702
Abstract
An ulcer that develops on the mucosal surface of the oral cavity is known as a mouth ulcer, also known as an oral ulcer or a mucosal ulcer. A mucus membrane ulcer is an open sore that is distinguished by the removal of [...] Read more.
An ulcer that develops on the mucosal surface of the oral cavity is known as a mouth ulcer, also known as an oral ulcer or a mucosal ulcer. A mucus membrane ulcer is an open sore that is distinguished by the removal of inflammatory dead tissue. The most typical type of oral ulcer is aphthous stomatitis. This investigation focuses on temperature-sensitive in situ gel formulations, which change their phase in response to body heat from liquid to semisolid gel. These are easily administered into the buccal cavity at the ulcer site and are a free-flowing liquid at room temperature. Utilizing various polymers, a temperature-sensitive in situ gel comprising phytoconstituents was developed utilising the cold technique. To optimise various types and concentrations of polymers, including carbopol, Poloxamer 188 (P 188), Poloxamer 407 (P 407), and others, preliminary research was conducted. For the formulation, 20% P 188 and 15% P 407 were employed because there is a correlation between the amount of poloxamers and thermogelling transition temperatures (Tsol-gel). A blend of phytoconstituents found in the extracts of Glycyrrhizin glabra and Psidium guava is used in the formulation of mouth ulcers because, as we know, they have fewer negative effects than synthetic chemicals. The outcomes demonstrated improved homogeneity, stability, gelation temperature, and spreadability for the developed product, which was regarded as satisfactory. The created formulation can also lessen dose variation and treat oral ulcers in the most effective way, with improved patient compliance. Full article
(This article belongs to the Proceedings of The 8th International Electronic Conference on Medicinal Chemistry)
27 pages, 12614 KiB  
Article
The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in Human Volunteers
by Nourhan Hisham Shady, Abdullah H. Altemani, Faisal H. Altemani, Sherif A. Maher, Mahmoud A. Elrehany, Entesar Ali Saber, Ahmed M. Badawi, Fatma Mohamed Abd El-Mordy, Nada M. Mohamed, Mohammed A. S. Abourehab, Ahmed M. Sayed, Usama Ramadan Abdelmohsen and Soad A. Mohamad
Molecules 2022, 27(20), 7020; https://doi.org/10.3390/molecules27207020 - 18 Oct 2022
Cited by 10 | Viewed by 2584
Abstract
Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. [...] Read more.
Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1β, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-β levels and significantly downregulated TNF-α and IL-1β in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to diverse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis. Full article
(This article belongs to the Special Issue Novel Natural Compounds as Wound Healing Agents)
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<p>H<sub>2</sub>O<sub>2</sub> radical scavenging activity of <span class="html-italic">Corchorus olitorius</span> seed extract at different concentrations (1000, 500, 250, and 125 µg/mL). Bars represent mean ± standard deviation (SD). Significant difference between groups is analyzed by a two-way ANOVA test after normalization of variables by the Shapiro–Wilk test.</p>
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<p>Superoxide radical scavenging activity of <span class="html-italic">Corchorus olitorius</span> seed extract at different concentrations (1000, 500, 250, and 125 µg/mL). Bars represent mean ± SD (standard deviation). Significant difference between groups is analyzed by a Two-way ANOVA test after normalization of variables by the Shapiro Wilk test.</p>
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<p>The activity of Corchorus olitorius seed extract and Mebo on excisional wounds on days 0, 3, 7, 10, and 14 post-wounding in the wound of adult male New Zealand Dutch strain albino rabbits, group 1: untreated (bare group), group 2: <span class="html-italic">Corchorus olitorius</span> seed extract-treated group and group 3: Mebo-treated group as a positive control group.</p>
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<p>Wound closure rates in all tested groups (group 1: untreated group bare control (<span class="html-italic">n</span> = 8), group 2: <span class="html-italic">Corchorus olitorius seed extract</span>-treated group (<span class="html-italic">n</span> = 8), group 3: Mebo-treated group (<span class="html-italic">n</span> = 8)) over time post-injury (0, 3, 7, 10, and 14 days). Significant difference between groups is analyzed by a two-way ANOVA test after normalization of variables by the Shapiro–Wilk test. Data were expressed as mean ± SD. * <span class="html-italic">p</span> ≤ 0.001 compared with those of the untreated group on the respective day and # <span class="html-italic">p</span> ≤ 0.001 compared with those of the Mebo group on the respective day.</p>
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<p>Gene expression in wound tissues for rabbits of different groups via quantitative RT-PCR. It was used to evaluate the gene expression in wound tissues for rabbits of different groups. Data represent fold change relative to the normal control group expression after normalization to glyceraldehyde 3-phosphate dehydrogenase (<span class="html-italic">GAPDH</span>). Bars represent mean ±SD. Significant difference between groups is analyzed by a two-way ANOVA test, where: * <span class="html-italic">p</span> ≤ 0.001 compared with those of the untreated group on the respective day.</p>
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<p>Gene expression in wound tissues for rabbits of different groups. Quantitative RT-PCR was used to evaluate the gene expression in wound tissues for rabbits of different groups. Data represent fold change relative to the normal control group expression after normalization to glyceraldehyde 3-phosphate dehydrogenase (<span class="html-italic">GAPDH</span>). Bars represent mean ± SD. Significant difference between groups is analyzed by a two-way ANOVA test, where: * <span class="html-italic">p</span> ≤ 0.001 compared with those of the untreated group on the respective days.</p>
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<p>Wounded skin 7 days after incision; [untreated group] (<span class="html-italic">n</span> = 8), showing the wound filled with blood clots (thick arrow) and the underlying sloughed granulation tissue with compact and disorganized collagen bundles (stars). [Mebo-treated group] (<span class="html-italic">n</span>= 8), showing scar tissue blocking the wound (thick arrow), the underlying dermal matrix showing inflammatory cellular infiltration mainly macrophages with acidophilic cytoplasm (black arrows in the inset) and coarse wavy collagen bundles packing the defect resembling that of the adjacent normal dermis (crosses). [<span class="html-italic">C. olitorius</span> seed-treated group] (<span class="html-italic">n</span> = 8), Showing marked re-epithelization and the underlying regenerated papillary dermal tissue showing fine interlacing collagen bundles (stars), and in the reticular dermis appear as coarse wavy bundles with numerous fibroblasts (yellow arrows in the inset). (H &amp; E stain ×200 and 400).</p>
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<p>Wounded skin 14 days after incision; [untreated group] (<span class="html-italic">n</span> = 8), showing the wide wound area (thick arrow) and the dermis underneath showing heavy inflammatory cellular infiltration and the blood vessels appear dilated and congested (arrows). [Mebo-treated group] (<span class="html-italic">n</span> = 8), showing typical epidermis and the underlying dermis with coarse and compact collagen bundles arranged in different directions (asterisks). Newly formed hair follicles (HF). [<span class="html-italic">C. olitorius</span> seed-treated group] (<span class="html-italic">n</span> = 8), showing typical stratified squamous keratinized epithelium and the collagen in the papillary dermis appearing as fine interlacing bundles (stars), and in the reticular layer appearing as coarse and wavy bundles (asterisks). Notice the newly formed hair follicles (HF). (H &amp; E stain ×200 and 400).</p>
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<p>Film dimensions and its adhesion to the buccal mucosal membrane.</p>
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<p>Scanning electron microscopic of the plain film (<b>A</b>), and drug-loaded film (<b>B</b>).</p>
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<p>Daily progress in RAMU healing in (<b>A</b>) intervention group, (<b>B</b>) control group.</p>
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<p>The 2D and 3D molecular docking presentation of the possible binding conformations of <b>19</b> (<b>A</b>,<b>B</b>), <b>20</b> (<b>C</b>,<b>D</b>), and <b>21</b> (<b>E</b>,<b>F</b>) in the <span class="html-italic">TNF-α</span> active site using PDB 2AZ5. The interacting residues are highlighted in the yellow stick model with H-bonds and H-pi interactions are presented as green and red dotted lines, respectively, having their distances illustrated in Å.</p>
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<p>The 2D and 3D molecular docking presentation of the possible binding conformations of <b>19</b> (<b>A</b>,<b>B</b>), <b>20</b> (<b>C</b>,<b>D</b>), and <b>21</b> (<b>E</b>,<b>F</b>) in the <span class="html-italic">TNF-α</span> active site using PDB 2AZ5. The interacting residues are highlighted in the yellow stick model with H-bonds and H-pi interactions are presented as green and red dotted lines, respectively, having their distances illustrated in Å.</p>
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<p>The 2D and 3D molecular docking presentation of the possible binding conformations of <b>19</b> (<b>A</b>,<b>B</b>), <b>20</b> (<b>C</b>,<b>D</b>), and <b>21</b> (<b>E</b>,<b>F</b>) in the <span class="html-italic">IL-1β</span> binding site using PDB 6Y8M. The interacting residues are highlighted in the yellow stick model with H-bonds and H-pi interactions are presented as green and red dotted lines, respectively, having their distances illustrated in Å.</p>
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<p>The 2D and 3D molecular docking presentation of the possible binding conformations of <b>19</b> (<b>A</b>,<b>B</b>), <b>20</b> (<b>C</b>,<b>D</b>), and <b>21</b> (<b>E</b>,<b>F</b>) in the <span class="html-italic">IL-1β</span> binding site using PDB 6Y8M. The interacting residues are highlighted in the yellow stick model with H-bonds and H-pi interactions are presented as green and red dotted lines, respectively, having their distances illustrated in Å.</p>
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<p>The 2D presentations of the molecular interaction of <b>14</b> (<b>A</b>), <b>16</b> (<b>B</b>), <b>19</b> (<b>C</b>), and <b>20</b> (<b>D</b>) with <span class="html-italic">GSK3</span> using PDB 1Q5K.</p>
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<p>The 3D presentations of the molecular interaction of <b>16</b> (<b>A</b>) and <b>20</b> (<b>B</b>) with <span class="html-italic">GSK3</span> using PDB 1Q5K are illustrated as a green stick model. The interacting amino acids of the binding domain are shown in yellow with the formed H-bonds and H-arene appearing as a green and red dotted line, respectively, with their corresponding distance in Å.</p>
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