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A high protein walnut flour (HPWF) was obtained by defatting walnut flour (WF), which is a by-product of the oil industry. The objective of this study was the chemical and techno-functional characterization of HPWF. Composition, amino acid content, protein secondary structure, protein solubility and thermal transitions were measured. Besides, the techno-functional properties, emulsion activity and stability, and water holding and oil absorption capacities, of HPWF were evaluated. Also, the molecular mass of proteins under denaturing conditions and the microstructure of HPWF were evaluated by electrophoresis and confocal scanning laser microscopy, respectively. HPWF had 55.4% protein content and 21.5% total dietary fibre. In terms of HPWF amino acid composition, the limiting amino acids were the sulphurated cysteine and methionine. By FTIR analysis, the main secondary structures were ß-sheet (49%) followed by α-helix (24%); both structures are considered to be ordered. Likewise, HPWF soluble proteins increased at basic pH and HPWF proteins were separated in 11 bands with molecular masses ranging from 97 kDa to 18 kDa by electrophoresis. With respect to techno-functional properties, HPWF presented good emulsion activity (51%) and high thermal emulsion stability (46%). In addition, HPWF retained 571% and 242% of water and oil by weight, respectively. Finally, the micrograph showed the predominance of protein structures and fibre fragments, and the presence of few lipids mostly trapped. These results showed that HPWF is an interesting source of plant-based proteins and walnut flour can be used to obtain high protein ingredients from non-traditional sources.
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Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).
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Bacterial communication, Quorum Sensing (QS), is a target against virulence and prevention of antibiotic-resistant infections. 16 derivatives of Piperlongumine (PL), an amide alkaloid from Piper longum L., were screened for QS inhibition. PL-18 had the best QSI activity. PL-18 inhibited the lasR-lasI, rhlR-rhlI, and pqs QS systems of Pseudomonas aeruginosa. PL-18 inhibited pyocyanin and rhamnolipids that are QS-controlled virulence elements. Iron is an essential element for pathogenicity, biofilm formation and resilience in harsh environments, its uptake was inhibited by PL-18. Pl-18 significantly reduced the biofilm biovolume including in established biofilms. PL-18-coated silicon tubes significantly inhibited biofilm formation. The transcriptome study of treated P. aeruginosa showed that PL-18 indeed reduced the expression of QS and iron homeostasis related genes, and up regulated sulfur metabolism related genes. Altogether, PL-18 inhibits QS, virulence, iron uptake, and biofilm formation. Thus, PL-18 should be further developed against bacterial infection, antibiotic resistance, and biofilm formation.
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The quantitative analysis of pulsed-chemical exchange saturation transfer (CEST) using a full model-based method is computationally challenging, as it involves dealing with varying RF values in pulsed saturation. A power equivalent continuous approximation of B1 power was usually applied to accelerate the analysis. In line with recent consensus recommendations from the CEST community for pulsed-CEST at 3T, particularly recommending a high RF saturation power (B1 = 2.0 µT) for the clinical application in brain tumors, this technical note investigated the feasibility of using average power (AP) as the continuous approximation. The simulated results revealed excellent performance of the AP continuous approximation in low saturation power scenarios, but discrepancies were observed in the z-spectra for the high saturation power cases. Cautions should be taken, or it may lead to inaccurate fitted parameters, and the difference can be more than 10% in the high saturation power cases.
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Background: Parametrial infiltration (PMI) is an important indicator for staging and treatment of cervical cancer (CC). The potential of amide proton transfer-weighted (APTw) parameters of peritumor tissue in predicting PMI is still uncertain. This study aims to explore whether the APTw parameters of peritumor tissue can improve diagnostic value of diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI). Methods: Eighty-one patients with pathologic analysis-confirmed CC were enrolled in this retrospective study. All patients underwent APTw MRI and DWI. The APTw values of tumor (APTw-t), APTw values in peritumor tissues (APTw-p) and apparent diffusion coefficient (ADC) values were independently reviewed by two radiologists to map the regions of interest and measure the corresponding values. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results: The study patients were divided into the PMI group (n=22) and non-PMI group (n=59). The APTw-t and APTw-p values (%) of PMI group were higher than those of the non-PMI group [3.71 (interquartile range, IQR, 3.60-3.98) and 2.75 (IQR, 2.68-2.77) vs. 3.33 (IQR, 3.24-3.60) and 1.98 (IQR, 1.82-2.36); P<0.001]. The ADC values of PMI group were lower than those of non-PMI group [0.88 (IQR, 0.83-0.94) ×10-3 vs. 0.95 (IQR, 0.88-1.04)×10-3 mm2/sec; P<0.001]. The area under the curve (AUC) of APTw-t, APTw-p and ADC value for PMI diagnosis were 0.810, 0.831 and 0.806 respectively. In addition, the AUC value (0.918) of APTw-p + ADC was optimal, with a sensitivity and specificity of 91.20% and 87.20% respectively. Conclusions: APTw in peritumor tissues, combined with ADC value can be used to efficiently distinguish PMI of CC.
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Herein, we report the inaugural instance of NHSi-coordinated copper amide emitters (2-5). These complexes exhibit thermally activated delayed fluorescence (TADF) and singlet-triplet dual emission in anaerobic conditions. The NHSi-Cu-diphenylamide (2) complex demonstrates TADF with a very small ΔEST gap (0.01 eV), an absolute quantum yield of 11%, a radiative rate of 2.55×105 s-1, and a short τTADF of 0.45 µs in the solid state. The dual emissive complexes (3-5) achieve an absolute quantum yield of up to 20% in the solid state with a kISC rate of 1.82×108 s-1 and exhibit room temperature phosphorescence (RTP) with lifetimes up to 9 ms. The gradual decrease in the intensity of the triplet state of complex 3 under controlled oxygen exposure demonstrates its potential for future oxygen-sensing applications. Complexes 2 and 3 have been further utilized to fabricate converted LEDs, paving the way for future OLED production using newly synthesized NHSi-Cu-amides.
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Determining the reliability of nanofiltration (NF) membranes for the removal of contaminants of emerging concern, including polyfluoroalkyl substances (PFASs), pharmaceuticals, and personal care products (PPCPs), is important for ensuring drinking water safety. This study aimed to clarify the factors that influence the removal of nine major PFASs during submerged NF treatment via extrapolation based on the factors that influence PPCP removal. The rejection of nine PFASs in ultra-filtered dam water by a polypiperazine-amide (NF270) membrane increased from 71 % to 94 % at a low permeate flux of 5 L/m2 h as the PFAS molecular dimensions increased. PFASs with a carboxylic acid (-CO2H) were rejected to a greater extent than PFASs with a sulfo group (-SO3H). Further, negatively charged PFASs or PPCPs were rejected to a greater extent than uncharged and positively charged PPCPs. Our findings suggest that the rejection of PFASs can vary because of the (i) clearance distance between the PFASs' molecular dimensions and NF membrane pore diameter and (ii) intensity of electrostatic repulsion between the PFASs' functional groups and NF membrane surface. Our study indicates that submerged NF can achieve high PFAS rejection; however, variations in rejection among PFASs can become more prominent owing to a low permeate flux.
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Residual chlorine from widespread disinfection processes forms byproducts in water that are harmful to humans and ecosystems. Portable sensors are essential tools for the on-site monitoring of residual chlorine in environmental samples. Here, an inexpensive colorimetric sensor was developed by grafting via amidation the chromogen orthotolidine (OTO) to the surface of a TEMPO-oxidized cellulose filter paper (O-TOFP). A thorough characterization of the sensor strip demonstrated that it was highly stable and that it could be stored for a long period before usage. O-TOFP had a fast response time of 30 s, was highly selective for residual chlorine ions (ClO-) with an accuracy of at least 95 %, and exhibited an excellent limit of detection of only 0.045 mg/L when combined with smartphone image acquisition. With its many positive features, the easy-to-use and robust O-TOFP sensor described here could become a useful tool for the determination of residual chlorine in different water samples.
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Treating the amide acetanilide (N-phenylacetamide, C8H9NO) with aqueous strong acids allowed the structures of five hemi-protonated salt forms of acetanilide to be elucidated. N-(1-Hydroxyethylidene)anilinium chloride-N-phenylacetamide (1/1), [(C8H9NO)2H][Cl], and the bromide, [(C8H9NO)2H][Br], triiodide, [(C8H9NO)2H][I3], tetrafluoroborate, [(C8H9NO)2H][BF4], and diiodobromide hemi(diiodine), [(C8H9NO)2H][I2Br]·0.5I2, analogues all feature centrosymmetric dimeric units linked by O-H...O hydrogen bonds that extend into one-dimensional hydrogen-bonded chains through N-H...X interactions, where X is the halide atom of the anion. Protonation occurs at the amide O atom and results in systematic lengthening of the C=O bond and a corresponding shortening of the C-N bond. The size of these geometric changes is similar to those found for hemi-protonated paracetamol structures, but less than those in fully protonated paracetamol structures. The bond angles of the amide fragments are also found to change on protonation, but these angular changes are also influenced by conformation, namely, whether the amide group is coplanar with the phenyl ring or twisted out of plane.
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Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.
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A critical consideration in the application of phytoremediation to remediate sludge soil contaminated with heavy metals is the potential for leaching risks that prevail prior to the efficient uptake of these metals by plants. The most cost-effective method is to use heavy metal stabilizers with selective adsorption. A novel amide-based COF material (COF-TH) has been synthesized as a heavy metal stabilizer for Pb. COF-TH exhibits significant selectivity for Pb in five-metal-mixed solutions, with a distribution coefficient KD as high as 3279 mL·g-1, which was more than 7.3 times that of other heavy metals. The maximum adsorption capacity of COF-TH for Pb was 189 mg·g-1. The adsorption fitted Langmuir model and intra-particle diffusion model, and satisfied pseudo-second-order kinetic model. The excellent selectivity and adsorption performance originate from the complexation between abundant amide groups and Pb ions. Pot experiments and leaching assays confirm that COF-TH decreased Pb leachate concentrations by 77.8 % without significantly decreasing total phytoextracted amounts of other heavy metals, due to the high selectivity of COF-TH to Pb. Additionally, its positive impact on plant growth and microbial diversity makes it a promising soil remediation agent. This investigation offers a novel approach to mitigate the leaching risk of a specific heavy metal Pb during sludge land application by integrating soil phytoremediation with stabilization techniques.
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We report the MRI findings of a patient with an atypical meningioma who presented with spontaneous infarction. A 67-year-old man with histories of recurrent meningioma complained of left ocular protrusion and a subsequent biopsy revealed atypical meningioma. Contrast-enhanced CT showed a uniformly enhancing tumour in the left ethmoid sinus, but MRI 2 days later showed no enhancement on Gd-T1WI and severe diffusion restriction on DWI, indicating spontaneous infarction. APT-CEST imaging showed slight hypointensity in comparison to the normal brain with a mean MTR asymmetry value of 0.48%. Tumour regrowth was confirmed on MRI after 2 months. The recurrent tumour showed moderate diffusion restriction on DWI and hyperintensity with a mean MTR asymmetry value of 2.59% on APT-CEST imaging. The decreased signal on APT-CEST at the time of spontaneous infarction may have been attributed to intratumoral acidosis and loss of viable tumour. APT-CEST imaging is useful for evaluating the intratumoral condition and tumour viability of the infarcted or ischemic tumour.
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BACKGROUND: Differentiation of glioma and solitary brain metastasis (SBM), which requires biopsy or multi-disciplinary diagnosis, remains sophisticated clinically. Histogram analysis of MR diffusion or molecular imaging hasn't been fully investigated for the differentiation and may have the potential to improve it. METHODS: A total of 65 patients with newly diagnosed glioma or metastases were enrolled. All patients underwent DWI, IVIM, and APTW, as well as the T1W, T2W, T2FLAIR, and contrast-enhanced T1W imaging. The histogram features of apparent diffusion coefficient (ADC) from DWI, slow diffusion coefficient (Dslow), perfusion fraction (frac), fast diffusion coefficient (Dfast) from IVIM, and MTRasym@3.5ppm from APTWI were extracted from the tumor parenchyma and compared between glioma and SBM. Parameters with significant differences were analyzed with the logistics regression and receiver operator curves to explore the optimal model and compare the differentiation performance. RESULTS: Higher ADCkurtosis (P = 0.022), frackurtosis (P<0.001),and fracskewness (P<0.001) were found for glioma, while higher (MTRasym@3.5ppm)10 (P = 0.045), frac10 (P<0.001),frac90 (P = 0.001), fracmean (P<0.001), and fracentropy (P<0.001) were observed for SBM. frackurtosis (OR = 0.431, 95%CI 0.256-0.723, P = 0.002) was independent factor for SBM differentiation. The model combining (MTRasym@3.5ppm)10, frac10, and frackurtosis showed an AUC of 0.857 (sensitivity: 0.857, specificity: 0.750), while the model combined with frac10 and frackurtosis had an AUC of 0.824 (sensitivity: 0.952, specificity: 0.591). There was no statistically significant difference between AUCs from the two models. (Z = -1.14, P = 0.25). CONCLUSIONS: The frac10 and frackurtosis in enhanced tumor region could be used to differentiate glioma and SBM and (MTRasym@3.5ppm)10 helps improving the differentiation specificity.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/patología , Glioma/diagnóstico por imagen , Glioma/patología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Diagnóstico Diferencial , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Curva ROC , Imagen por Resonancia Magnética/métodosRESUMEN
The one-step synthesis of tetra-substituted benzenes was accomplished via gold-catalyzed diyne-ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co-catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold-catalyzed alkyne activation processes.
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Benzophenone skeletons containing a carbonyl unit (O=C) have been widely used as electron acceptors in the thermally activated delayed fluorescence (TADF) materials. Herein, we present a novel molecular design concept for TADF materials by transitioning from a carbonyl to an amide (O=C-N) skeleton as the acceptor. The amide unit, compared to its carbonyl counterpart, offers a more stable electronic configuration. Leveraging this insight, we have developed a series of high-performance TADF molecules based on benzoyl carbazole and carbazoline acceptors. These molecules exhibit exceptionally small singlet-triplet energy gaps and pronounced aggregation-enhanced emission properties, achieving photoluminescence quantum yields in neat films as high as 99%. Consequently, these materials serve as efficient emitters in non-doped organic light-eimtting diodes (OLEDs), reaching a maximum quantum efficiency (EQEmax) of up to 26.0%, significantly higher than the 17.0% obtained with benzophenone acceptor-based TADF molecules. Additionally, they have been used as TADF hosts in narrowband red fluorescent OLEDs, setting a record-high EQEmax of 22.4%.
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In small clinical studies, the application of transcranial photobiomodulation (PBM), which typically delivers low-intensity near-infrared (NIR) to treat the brain, has led to some remarkable results in the treatment of dementia and several neurodegenerative diseases. However, despite the extensive literature detailing the mechanisms of action underlying PBM outcomes, the specific mechanisms affecting neurodegenerative diseases are not entirely clear. While large clinical trials are warranted to validate these findings, evidence of the mechanisms can explain and thus provide credible support for PBM as a potential treatment for these diseases. Tubulin and its polymerized state of microtubules have been known to play important roles in the pathology of Alzheimer's and other neurodegenerative diseases. Thus, we investigated the effects of PBM on these cellular structures in the quest for insights into the underlying therapeutic mechanisms. In this study, we employed a Raman spectroscopic analysis of the amide I band of polymerized samples of tubulin exposed to pulsed low-intensity NIR radiation (810 nm, 10 Hz, 22.5 J/cm2 dose). Peaks in the Raman fingerprint region (300-1900 cm-1)-in particular, in the amide I band (1600-1700 cm-1)-were used to quantify the percentage of protein secondary structures. Under this band, hidden signals of C=O stretching, belonging to different structures, are superimposed, producing a complex signal as a result. An accurate decomposition of the amide I band is therefore required for the reliable analysis of the conformation of proteins, which we achieved through a straightforward method employing a Voigt profile. This approach was validated through secondary structure analyses of unexposed control samples, for which comparisons with other values available in the literature could be conducted. Subsequently, using this validated method, we present novel findings of statistically significant alterations in the secondary structures of polymerized NIR-exposed tubulin, characterized by a notable decrease in α-helix content and a concurrent increase in ß-sheets compared to the control samples. This PBM-induced α-helix to ß-sheet transition connects to reduced microtubule stability and the introduction of dynamism to allow for the remodeling and, consequently, refreshing of microtubule structures. This newly discovered mechanism could have implications for reducing the risks associated with brain aging, including neurodegenerative diseases like Alzheimer's disease, through the introduction of an intervention following this transition.
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Surface modification of drug-loaded particles with polyethylene glycol (PEG) chains is a powerful tool that promotes better transport of therapeutic agents, provides stability, and avoids their detection by the immune system. In this study, we used a new approach to synthesize a biodegradable poly(ester amide) (PEA) and PEGylating surfactant. These were employed to fabricate micro/nanoparticles with a core-shell structure. Nanoparticle (NP)-protein interactions and self-assembling were subsequently studied by synchrotron radiation-based FTIR microspectroscopy (SR-FTIRM) and transmission electron microscopy (TEM) techniques. The core-shell structure was identified using IR absorption bands of characteristic chemical groups. Specifically, the stretching absorption band of the secondary amino group (3300 cm-1) allowed us to identify the poly(ester amide) core, while the band at 1105 cm-1 (C-O-C vibration) was useful to demonstrate the shell structure based on PEG chains. By integration of absorption bands, a 2D intensity map of the particle was built to show a core-shell structure, which was further supported by TEM images.
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Nanopartículas , Poliésteres , Polietilenglicoles , Sincrotrones , Polietilenglicoles/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Nanopartículas/química , Poliésteres/química , Microscopía Electrónica de Transmisión/métodos , Amidas/químicaRESUMEN
The endocannabinoid system, known for its regulatory role in various physiological processes, relies on the activities of several hydrolytic enzymes, such as fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), monoacylglycerol lipase (MAGL), and α/ß-hydrolase domains 6 (ABHD6) and 12 (ABHD12), to maintain homeostasis. Accurate measurement of these enzymes' activities is crucial for understanding their function and for the development of potential therapeutic agents. Fluorometric assays, which offer high sensitivity, specificity, and real-time monitoring capabilities, have become essential tools in enzymatic studies. This review provides a comprehensive overview of the principles behind these assays, the various substrates and fluorophores used, and advances in assay techniques used not only for the determination of the kinetic mechanisms of enzyme reactions but also for setting up kinetic assays for the high-throughput screening of each critical enzyme involved in endocannabinoid degradation. Through this comprehensive review, we aim to highlight the strengths and limitations of current fluorometric assays and suggest future directions for improving the measurement of enzyme activity in the endocannabinoid system.
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Amidohidrolasas , Endocannabinoides , Pruebas de Enzimas , Endocannabinoides/metabolismo , Humanos , Pruebas de Enzimas/métodos , Amidohidrolasas/metabolismo , Amidohidrolasas/antagonistas & inhibidores , Hidrólisis , Monoacilglicerol Lipasas/metabolismo , Monoacilglicerol Lipasas/antagonistas & inhibidores , Animales , Fluorometría/métodos , Fluorescencia , Cinética , Colorantes Fluorescentes/química , Inhibidores Enzimáticos/farmacologíaRESUMEN
α-Glucosidase inhibitory activity of galbanic acid and its new amide derivatives 3a-n were investigated. Galbanic acid and compounds 3a-n showed excellent anti-α-glucosidase activity with IC50 values ranging from 0.3 ± 0.3 µM to 416.0 ± 0.2 µM in comparison to positive control acarbose with IC50 value of = 750.0 ± 5.6. In the kinetic study, the most potent compound 3h demonstrated a competitive mode of inhibition with Ki = 0.57 µM. The interaction of the most potent compound 3h with the α-glucosidase was further elaborated by in vitro Circular dichroism assessment and in silico molecular docking and Molecular dynamics studies. Compound 3h was also non-cytotoxic on human normal cells. In silico study on pharmacokinetics and toxicity profile of the most potent galbanic acid derivatives demonstrated that these compounds are valuable lead compounds for further study in order to achieve new anti-diabetic agents.
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Amidas , Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/síntesis química , alfa-Glucosidasas/metabolismo , Humanos , Relación Estructura-Actividad , Estructura Molecular , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Relación Dosis-Respuesta a Droga , Saccharomyces cerevisiae/enzimologíaRESUMEN
According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.