847


Localiza(on of E-cadherin and Vimen(n in Mucosal Ulcer Healing Treated by Vi(s 
Vinifera Seeds Oil in Rat Model 

Vol 13 No 1 (2025)    DOI 10.5195/d3000.2025.847 

 h#p://den*stry3000.pi#.edu 

Localization of E-cadherin and Vimentin in Mucosal Ulcer 
Healing Treated by Vitis Vinifera Seeds Oil in Rat Model 

Russol Faik, Nada M.H. Al-Ghaban 

College of Dentistry, University of Baghdad, Baghdad, Iraq

Abstract 

Objec&ve: The an(-inflammatory components generated by Vi(s vinifera (Grape) seeds oil (GSO) help 
reduce inflamma(on and accelerate the healing process when applied topically to an ulcer. The current 
study aimed to assess the expression of E-cadherin and Vimen(n during oral ulcer healing treated by 
GSO. 

Materials and Methods: Twenty-four albino male rats (350–450 g) were used for this study. The rats 
were slaughtered on the 5th and 10th days aKer an ulcer induc(on on either their leK or right cheek 
mucosa. The rats in the control group received sterile dis(lled water, whereas those in the experimental 
group received GSO for ulcers treatment. The (ssue samples were subsequently u(lized for histological 
and immunohistochemical inves(ga(ons of E-cadherin and Vimen(n. 

Results: Compared with the control group, the GSO-treated ulcer group presented significantly higher 
expression of E-cadherin and Vimen(n at days 5 and 10 than the control group, with some evidence of 
epithelial-mesenchymal transi(on (EMT) at 5 days in both groups. 

Conclusion: With the limita(on of this study, GS may accelerate the healing of mucosal ulcers, as 
demonstrated by increased expression of E-cadherin and Vimen(n. 

Clinical relevance: GSO can be used as a 
topical herbal modality for mucosal ulcer 
healing. 

Keywords: Vi(s vinifera seed oil (GSO), 
Mucosal ulcer, Vimen(n, E-cadherin, Rats, 
Healing, EMT. 

Cita;on: Faik R, et al. (2025) Localiza;on of E-cadherin 
and Vimen;n in Mucosal Ulcer Healing Treated by Vi;s 
Vinifera Seeds Oil in Rat Model. Den;stry 3000. 1:a001 
doi:10.5195/d3000.2025.847. 
Received: February 12, 2025  
Accepted: March 31, 2025 
Published: April 18, 2025 
Copyright: ©2025 Falk R, et al. This is an open access 
ar;cle licensed under a Crea;ve Commons A[ribu;on 
Work 4.0 United States License. 
Email: rusul.Abd2206@codental.uobaghdad.edu.iq  

 

 

Introduction 

The development of the 
extracellular matrix (ECM), 
migration, adhesion, proliferation, 
and differentiation are all steps in 
the multicellular process that 
constitutes wound healing [1]. The 
complex connections among many 
cell types, cytokines, and the 
circulatory system are involved in 
the wound-healing process. The 
initial cascade of vasoconstriction 
and platelet aggregation stops 
bleeding, and an influx of 
inflammatory cells, led by 
neutrophils in the initial stages, 
occurs. To encourage angiogenesis 

and re-epithelialization, fibroblasts 
then construct a framework by 
laying down extracellular 
components [2]. 

Phenolic compounds are plant 
secondary metabolites found in 
fruits, vegetables and beverages, 
including grapes, The beneficial 
health effects of grape and grape 
products and the anti-
inflammatory and protective 
effects of traditional grape 
preparations on the cardiovascular 
system are related to their 
bioactive phenolic compounds. 
The biological activities of grape 
phenolic compounds include 

among others anti-inflammatory, 
antioxidant and cardioprotective 
effects [3].  

Proanthocyanidin in grape seeds 
can target human keratinocytes 
and cause them to produce the 
vascular endothelial growth factor 
VEFG [4]. Owing to the high 
concentrations of vitamins, fatty 
acids, and phenolic compounds, 
grape seed oil (GSO) is beneficial 
to the food, pharmaceutical, and 
esthetic sectors. Grape seed oil 
may interact with cellular and 
molecular pathways; it has anti- 
inflammatory, antibacterial, and 
anticancer properties [5]. It is 



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composed of polyunsaturated 
fatty acids (PUFAs), with linoleic 
acid (C18:2) accounting for 58–
78% of the total [6]. This may 
inhibit oxidative stress by 
preventing the release of 
proinflammatory mediators by 
oxidized low-density lipoprotein-
stimulated macrophages [5]. The 
adhesion of cells in human 
epithelial tissues relies on 
adherent junctions, which are 
enhanced by the cell adhesion 
protein E-cadherin (E-cad) [7]. E-
cadherin is crucial in the wound 
healing process, including mitosis, 
maturation, and migration. In vitro 
research revealed that the 
upregulation of keratinocyte 
migration leads to the 
downregulation of E-cadherin 
expression [8]. 

Vimentin is an intermediate 
filament protein that contributes 
to cellular processes such as 
migration, morphology, plasticity, 
and organelle anchoring. In 
addition to its structural and 
cytoskeletal functions. 
Lymphocytes, fibroblasts, 
endothelial cells, macrophages, 
and melanocytes are 
mesenchymal cells that express 
vimentin [9]. Vimentin located on 
the cell surface has several 
functions in cell‒cell interactions, 
wound healing, migration, and 
immune system activation [10]. 

The epithelial‒mesenchymal 
transition (EMT) is caused by 
metabolic alterations that enable 
polarized epithelial cells to adopt a 
phenotype like that of 
mesenchymal cells. During this 
process, the cell's basal surface 
interacts with the basement 
membrane [11]. Typically, studies 
related to EMT have investigated 
the expression of epithelial 
markers (e.g., E-cadherin) and 
mesenchymal markers (e.g., N-
cadherin or vimentin) to 
characterize the process; 
however, conclusive experimental 
evidence for a real mesenchymal 
state as the endpoint is absent in 
several cases where the term EMT 
is employed [12]. The benefits of 
grape seed oil on the healing of 
oral ulcers have not been widely 
researched. Therefore, the 
purpose of this study is to 
investigate the curative process of 
an experimentally induced oral 
ulcer treated with grape seed oil in 
a rat by assessing the expression 
of E-cadherin and Vimentin 
monoclonal antibodies. 

Material and Methods 

The current study was approved 
by the Institutional Ethical 
Committee of Animal 
Experimentation of the (Blinded 
for review). The animals were kept 
under nursing and supervision 
from the staff of the animal house 

of the Medical Research Institute, 
City, for approximately 3 months, 
starting in November 2023 and 
ending in February 2024. In this 
study, the authors followed the 
Animal Research: Reporting in 
Vivo Experiments (ARRIVE) 
guidelines [13]. Grape seed extract 
has been approved as generally 
recognized as safe (GRAS) by the 
Food and Drug Administration 
(FDA) and is sold commercially as 
a dietary supplement listed in the 
Everything Added to Food in the 
United States (EAFUS) database. 
Bentivegna and Whitney reported 
that the no-observed- adverse-
effect level (NOAEL) of grape seed 
extracts determined in rats was 
1.78 g/kg body weight/day, and 
the normal amount of grape seed 
extract used in food applications 
was 0.01–1% [14]. 

The rats were housed in 
polypropylene enclosures within 
the experimental animal facility, 
maintaining consistent 
environmental conditions such as 
12-hour light‒dark cycles and a 
temperature of 24 ± 2 °C. The 
animals were given a rat chow 
pellet meal and were allowed free 
access to tap water. Before ulcer 
induction, the rats were allowed a 
one-week acclimation period to 
adjust to the laboratory 
environment. 



Localiza(on of E-cadherin and Vimen(n in Mucosal Ulcer Healing Treated by Vi(s Vinifera Seeds Oil in Rat 
Model 

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A total of twenty-four male albino 
rats, weighing between 250 and 
300 grams and aged two to three 
months, were used as 
experimental models. Twelve rats 
were allocated for each study 
duration (five and ten days). The 
rats were then randomly divided 
into two groups, a control group 
and a group treated with GSO. 
Female rats were specifically 
excluded because of cyclic 
hormonal variations and the 
potential for pregnancy 
throughout the experimental 
study. 

To determine the precise dosage 
of general anesthesia, the rats 
were weighed. Then, general 
anesthesia was induced via 
intraperitoneal injection of 
xylazine (5 mg/kg) and ketamine 
(50 mg/kg) [15]. After disinfection 
with 70% alcohol, ulcers were 
induced on both the right and left 
buccal mucosa via sterile round 
diamond burs, creating lesions 5 
mm in diameter and 1 mm deep 
(Figure 1), which were measured 
via a digital Vernier caliper [16].  

 

 

Figure 1. A photograph showing 
traumatic ulcer induction in the 
buccal mucosa. 

The treatment involved daily 
application of 30 µl of GSO (US 
ORGANIC, Amazon)" USDA 
Certified Organic & 100% Pure: 
Cold-pressed for maximum purity 
and nutrient retention, sourced 
from premium quality grapes, 
antioxidant-Rich: Rich in essential 
fatty acids like Oleic and Linoleic" 
(Figure 2) on the right side via a 
micropipette, whereas the left 
side received distilled water as a 
control. 

 

Figure 2. Vitis vinifera seed oil 
(GSO). 

The animals were euthanized on 
days 5 and 10 through the 
administration of an excessive 
amount of anesthetic solution 
[17]. The ulcerated regions were 
excised and extended 5 mm 
beyond the ulcer edge. After 
fixation in 10% neutral buffered 
formalin for 24 hours, the samples 
were washed [18]. The samples 

were dehydrated by placing them 
in increasing alcohol 
concentrations, then clarified in 
xylene, and finally embedded in 
paraffin wax. Sections (4 µm) were 
then subjected to hematoxylin and 
eosin (H&E) staining (Figure 3) and 
immunohistochemical analysis, 
which was performed under a light 
microscope, to evaluate mucosal 
ulcer healing. 

 

Figure 3. Histological progression 
of oral ulcers at two time points 
(day 5 and day 10) under 10X 
magnification. A) Control group on 
Day 5, B) GSO-treated group on 
Day 5, C) control group on Day 10, 
D) GSO-treated group on Day 10. 

Immunohistochemical analysis of 
E-cadherin and vimentin was 
carried out via monoclonal mouse 
anti-human E-cadherin, clone 
NCH-38 (Dako Company), England, 
and monoclonal mouse anti- 
vimentin, clone Vim 3B4 (Daco 
Company), England. 



Localiza(on of E-cadherin and Vimen(n in Mucosal Ulcer Healing Treated by Vi(s Vinifera Seeds Oil in Rat 
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Under a light microscope at x40, 
five fields were chosen from the 
epithelium area, and another five 
fields from the lamina propria 
from each tissue section were 
captured by a digital camera (5 
pixels), and the images evaluated 
were imported to a computer. 

The evaluation of the staining 
results was achieved by applying 
the Aperio positive pixel count 
algorithms program (from Aperio 
Image Scope software v11.1.2.760 
developed by Aperio Technologies 
Inc., USA), and we neglected the 
yellow color, which represents a 
weak positive reading [1,19,20]. 
The average mean positive 
percentages for each of the five 
areas from the epithelium and 
lamina propria were obtained and 
considered the value of the 
expression of both E-cadherin and 
vimentin. 

The data obtained from the 
immunohistochemical 
examination were assessed for 
normality via the Shapiro‒Wilk 
test. Numeric values are 
presented as a range 
encompassing the minimum and 
maximum values, along with the 
mean, standard deviation, and 
median. When the variables 
exhibited a normal distribution, 
Student’s t test was used to 
compare two distinct groups. The 
predetermined level of 

significance for the findings was 
established at P=0.05. The data 
were analyzed via the IBM SPSS 
software package version 20.0. 

Results 

The control group on days 5 and 
10 presented mild to moderate 
membranous morphology with 
positive expression of E-cadherin 
in the newly formed basal, 
spinosum, and granulosum cells of 
the epithelium and negative 
expression in the keratinized layer. 
On the other hand, the endothelial 
cells and fibroblasts weakly 
positively expressed E-cadherin 
(Figure 4, A and B). The study 
group at both time points 
presented moderate to strong 
positive expression in all layers of 
the newly regenerated epithelium 
around the ulcer margin except 
the keratinized layer (Figure 3, C 
and D). In lamina propria, 
endothelial and fibroblasts 
presented moderate positive 
expression of E-cadherin, 
especially on day 5, in the control 
group (Figure 5). The expression 
levels of E-cadherin in the examine 
tissue samples are summarized in 
(Table 1). 

The control group at two time 
points (day 5 and day 10) after 
ulcer induction presented 
moderate cytoplasmic expression 
of vimentin in fibroblasts, 
endothelial cells, and 

inflammatory cells (Figure 6, A and 
B). However, the study group 
exhibited strong cytoplasmic 
expression of vimentin in 
fibroblasts, endothelial cells, and 
inflammatory cells at both time 
points (Figure 6, C and D). On the 
other hand, moderate positive 
expression was detected in the 
cytoplasm of the granulosum 
epithelial cell layer, especially in 
both groups, on day 5 (Figure 7). 
The distribution and intensity of 
vimentin expression in the studied 
samples are presented in (Table 
2). 

A comparative analysis of E-
cadherin and vimentin expression 
patterns is provided in (Table 3) 
demonstrate an inverse 
relationship between these 
markers. 

The correlation analysis between 
E-cadherin and vimentin 
expression levels is summarized in 
(Table 4). 

 

 



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Figure 4. A: Photomicrograph 
showing membranous positive 
expression of E-cadherin in the 
epithelial layer, DAB stain (40x), A) 
Control Day 5 B) Control day 10, C) 
Study day 5, D) Study day 10. 

Figure 5. Photomicrograph of the 
lamina propria of the rat oral 
mucosa showing moderate 
positive expression of E-cadherin 
in A and weak positive expression 
in B, C, and D. DAB staining at 40x. 

A) Control day 5. B) Control 
day 10. C) Study day 5. D) Study 
day 10. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A B 

C D 

D C 

B A 



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Figure 6. Immunohistochemical 
image showing strong positive 
cytoplasmic expression of 
vimentin in inflammatory cells, 
fibroblasts, and blood vessels in 
the lamina propria; vimentin DAB 
stain (40x). A) Control day 5, B) 
control day 10, C) study day 5, D) 
study day 10. 

Figure 7. Photomicrograph 
showing weakly positive 
expression of Vimentin in the 
granulosa layer of the epithelium 
in A, B, and C and strongly positive 
expression in D. DAB staining 
(40x): A) Control Day 5 B) Control 
Day 10 C) Study Day 5 D) Study 
day 10. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

D C 

A B 

D C 

B A 



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Table 1. Comparison of E-cadherin expression in the epithelium and lamina propria between the studied groups.

 

 

 

 

 

 

 

 

 

 

 

 

Table 2. Comparison of the expression of vimentin in the epithelium and lamina properties

between the studied groups. 

day site control  study  T test P-value 

Mean SD Mean SD 

5th Epithelium 27.29 3.5 49.05 4.32 -13.56 0.000*1 

Lamina 
properia 

41.09 2.93 71.09 3.17 -24.059 0.000*1 

10th Epithelium 36.70 1.83 56.51 3.55 -4.158 0.000*2 

Lamina 

properia 

54.93 3.27 82.77 1.67 -26.233 0.000*2 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

day site control study T test P value 

Mean SD Mean SD 

5th Epithelium 56.95 3.26 71.31 3.57 -10.291 0.000*2 

Lamina properia 26.71 4.73 19.10 4.53 3.292 0.000*1 

10th Epithelium 60.74 2.28 80.37 1.79 -23.434 0.000*2 

Lamina properia 12.36 1.66 13.63 2.22 -1.585 0.127*2 



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Table 3. Comparison of E-cadherin and vimentin markers. 

Day Group Layer Mean differnce±SE T test P value 

 
Day 5 

Control 
Epithelium 29.66±1.38 21.495 0.000*1 

Lamina properia -14.38±1.61 -3.927 0.000*2 

Study 
Epithelium 22.27±1.62 13.768 0.000*1 

Lamina properia -51.99±1.60 -32.569 0.000*1 

 
Day 10 

Control 
Epithelium 24.04±0.85 28.446 0.000*1 

Lamina properia -42.57±1.06 -40.187 0.000*1 

Study 
Epithelium 23.86±1.15 4.158 0.000*2 

Lamina properia -69.15±0.8 -86.141 0.000*1 
 

Table 4. Correlations between E-cadherin and vimentin marker. 

Day Group Layer r P value 

 
Day 5 

Control 
Epithelium 0.035 0.9151 

Lamina properia -0.165 0.6092 

Study 
Epithelium 0.148 0.6461 

Lamina properia 0.031 0.9251 

 
Day 10 

Control 
Epithelium 0.028 0.9321 

Lamina properia 0.241 0.4511 

Study 
Epithelium 0.329 0.2962 

Lamina properia 0.417 0.1771 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



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Discussion 

The current study chose 
laboratory Albino rats because of 
their physiological similarity to 
humans, making them a practical 
model for evaluating the dynamics 
of the mucosal healing process 
[21]. Traumatic ulcers were 
induced with a diamond bur 5 mm 
in diameter, which reflects the 
common clinical similarity with 
mucosal injury [22]. The 
development of mucosal 
inflammation has frequently been 
suggested to be influenced by a 
loss of epithelial barrier function 
[23]. Currently, herbal medicine 
represents a significant aspect of 
complementary and alternative 
medical practices. The therapeutic 
use of herbs in wound and injury 
management has been well-
established since the dawn of 
ancient civilizations [24]. 

 Previous studies have shown that 
the therapeutic efficacy of the 
GSO accelerates mucosal healing 
by enhancing wound closure, 
reducing inflammation, and 
accelerating the restoration of 
epithelial integrity [25]. This 
finding is consistent with our 
finding that ulcers treated 
topically with GSO accelerated 
wound healing better than that in 
the control one. 

 

Moreover, GSO significantly 
increased the expression of E-
cadherin and vimentin compared 
with the control group. This may 
be because of the phenolic 
compounds, fatty acids, and 
vitamins present in the oil, which 
act as anti-inflammatory and 
antioxidant agents [26]. 

The present study revealed strong 
membranous expression of E-
cadherin in almost all the 
epithelial layers except the 
keratinized layer.  

This finding coincided with 
previously observed moderate to 
strong (2+/3+) membranous E-
cadherin staining observed in the 
epithelial cells of the oral cavity 
[27]. In a previous study [28], E-
cadherin was highly expressed in 
normal mucosal tissue. Intense 
staining of E- cadherin was 
observed in the spinous and basal 
cell layers, this finding correlates 
with our results. 

Vimentin is a type III intermediate 
filament protein exclusively 
expressed in mesenchymal cells. 
Because Vimentin is naturally 
observed in the lamina propria, 
Vimentin facilitates the 
integration, response, and 
perception of microenvironmental 
stimuli by cells [29]. Greater 
expression was observed in the 
GSO group than in the control 
group, which was confirmed 

previously [30]. The immortalized 
keratinocyte cell line exhibited 
significantly elevated levels of 
vimentin when cocultured with 
both normal and keloid-derived 
fibroblasts in the extracellular 
matrix (ECM). 

However, several investigations 
have recorded the temporary 
stimulation of vimentin expression 
in epithelial cells in response to 
certain pathological or 
physiological situations that 
require epithelial cell motility. 
Consequently, vimentin has been 
used as an indicator of the 
migratory state of epithelial cells 
[31]. Our results demonstrate that 
vimentin is expressed in the 
granulosum layer of the 
epithelium, which matches 
previous findings [30], with 
epidermal cells not differentiating 
into fibroblasts but having a 
fibroblast-like phenotype. 
Additionally, abnormal vimentin 
expression in the oral epithelium 
of premalignant lesions and weak 
vimentin immunoreactivity in the 
cytoplasm of suprabasal epithelial 
cells was previously reported [32]. 
The production of vimentin in 
epithelial cells may induce early 
molecular alterations in both the 
epithelial and mesenchymal 
compartments. 

The expression of vimentin in the 
epithelial layer may be linked to 



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the appearance of cells exhibiting 
a mesenchymal phenotype inside 
an epithelial sheet, which is 
generally referred to as epithelial-
to-mesenchymal transition (EMT) 
which results from the 
transformation of endogenous 
epithelial cells [33,34]. 

The epithelial-mesenchymal 
transition (EMT) is a crucial 
process requiring two key 
proteins, E- cadherin and 
vimentin, known for their varied 
expression and unique roles in this 
transition. The cytoplasm was 
positively stained with vimentin, 
whereas the cell membrane was 
positively stained with E-cadherin. 
During EMT, cellular phenotypes 
change quickly and may be 
reversed. In contrast, epithelial 
cells change their polarity and 
cytoskeleton by losing adhesion 
junctions. E-cadherin is recognized 
for maintaining the integrity of 
epithelial cells and plays a crucial 
role in cell differentiation. 
Vimentin is a cytoskeletal protein 
present in endothelial cells, 
fibroblasts, and leukocytes, among 
other cell types. It is absent in 
normal epithelial cells and 
contributes to EMT [35]. 

In the present study, after re-
epithelization, complete ulcer 
healing, and strong expression of 
Vimentin in the epithelial layers on 
day 10 in the GSO group may be 

due to mesenchymal-to- epithelial 
transition (MET) may occur to help 
in wound healing and restores 
epithelial layers. As an organism's 
body plan develops, the MET plays 
a role in several stages of 
morphogenesis and 
organogenesis. It occurs in 
intermittent alternation with the 
EMT. MET controls epithelial 
creation throughout embryonic 
development, whereas 
mesenchymal cells gradually 
achieve apicobasal polarity [36]. 

 

Conclusion 

The topical application of GSO 
effectively treated experimentally 
induced buccal mucosal ulcers in 
rats by promoting their 
proliferation, as shown by 
alterations in the expression of E-
cadherin and vimentin. 
Continuous treatment for 10 days 
increased the expression of E-
cadherin and vimentin, with 
significant differences observed 
between the control and study 
groups. In the current study, the 
expression of the epithelial marker 
E-cadherin was detected strongly 
in epithelial cells with weak 
intensity in the lamina properia. In 
contrast, the mesenchymal marker 
vimentin was identified in lamina 
properia with weak intensity in 
epithelial cells. EMT and MET may 
explain this; however, this finding 

requires validation via several 
future investigations. 

Conflicts of interest 

The authors declare no competing 
interest. 

References 

1. Abd SS, Al-Ghaban NMH. The 
epidermal growth factor receptor 
expression in leptin-treated 
traumatic oral ulcer in rats. JGPT. 
2020. 
doi:10.13140/RG.2.2.33703.7824. 

2. Ozgok Kangal MK, Regan JP. 
Wound healing. Treasure Island 
(FL): StatPearls Publishing; 2023 
May 1. 

3. Ardid-Ruiz A, Harazin A, Barna L, 
Walter FR, Bladé C, Suárez M, et 
al. The effects of Vitis vinifera L. 
phenolic compounds on a blood-
brain barrier culture model: 
Expression of leptin receptors and 
protection against cytokine-
induced damage. J 
Ethnopharmacol. 
2020;247:112253. 
doi:10.1016/j.jep.2019.112253. 

4. Abd Alrazaq MH, Al-Ghaban 
NMH. Immunohistochemical 
localization of bone morphogenic 
protein-2 in extracted tooth 
socket treated by local application 
of grape seeds oil in rabbits. 
Biochem Cell Arch. 2020;20:581. 
doi:10.35124/bca.2020.20.1.581. 

5. Garavaglia J, Markoski MM, 
Oliveira A, Marcadenti A. Grape 
seed oil compounds: biological 
and chemical actions for health. 



Localiza(on of E-cadherin and Vimen(n in Mucosal Ulcer Healing Treated by Vi(s Vinifera Seeds Oil in Rat 
Model 

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 h#p://den*stry3000.pi#.edu 

Nutr Metab Insights. 2016;9:59–
64. doi:10.4137/NMI.S32910. 

6. Bellili S, Jazi S, Nasr S, et al. 
Grape seed oil: Chemical 
composition, biological properties 
and health benefits. 2018. ISBN: 
978-153613561-9. 

7. Abe-Yutori M, Chikazawa T, 
Shibasaki K, Murakami S. 
Decreased expression of E-
cadherin by Porphyromonas 
gingivalis-lipopolysaccharide 
attenuates epithelial barrier 
function. J Periodontal Res. 
2016;52(1):42–50. 
doi:10.1111/jre.12367. 

8. Grabenstetter A, Mohanty AS, 
Rana S, Zehir A, Brannon AR, 
D'Alfonso TM, et al. E-cadherin 
immunohistochemical expression 
in invasive lobular carcinoma of 
the breast: correlation with 
morphology and CDH1 somatic 
alterations. Hum Pathol. 
2020;102:44–53. 
doi:10.1016/j.humpath.2020.06.0
02. 

9. Arrindell J, Desnues B. Vimentin: 
from a cytoskeletal protein to a 
critical modulator of immune 
response and a target for 
infection. Front Immunol. 
2023;14:1224352. 
doi:10.3389/fimmu.2023.122435. 

10. Ramos I, Stamatakis K, Oeste 
CL, Pérez-Sala D. Vimentin as a 
multifaceted player and potential 
therapeutic target in viral 
infections. Int J Mol Sci. 
2020;21(13):4675. 
doi:10.3390/ijms21134675. 

11. Kalluri R, Weinberg RA. The 
basics of epithelial–mesenchymal 
transition. J Clin Invest. 
2009;119(6):1420–8. 
doi:10.1172/JCI39104. 

12. Haensel D, Dai X. Epithelial-to-
mesenchymal transition in 
cutaneous wound healing: Where 
we are and where we are heading. 
Dev Dyn. 2018;247(3):473–80. 
doi:10.1002/dvdy.24561. 

13. Kilkenny C, Browne W, Cuthill 
IC, Emerson M, Altman DG. Animal 
research: reporting in vivo 
experiments: the ARRIVE 
guidelines. Br J Pharmacol. 
2010;160(7):1577–9. 

14. Ma ZF, Zhang H. 
Phytochemical constituents, 
health benefits, and industrial 
applications of grape seeds: A 
mini-review. Antioxidants. 
2017;6(3):71. 
doi:10.3390/antiox6030071. 

15. Giroux MC, Hélie P, Burns P, 
Vachon P. Anesthetic and 
pathological changes following 
high doses of ketamine and 
xylazine in Sprague Dawley rats. 
Exp Anim. 2015;64(3):253–60. 
doi:10.1538/expanim.14-0088. 

16. Wang X, Yan L, Tang Y, He X, 
Zhao X, Liu W, et al. Anti-
inflammatory effect of HGF 
responses to oral traumatic ulcers 
using an HGF-Tg mouse model. 
Exp Anim. 2022;71(2):204–13. 
doi:10.1538/expanim.21-0141. 

17. Mohamed IF, Ghani BA, Fatalla 
AA. Histological evaluation of the 
effect of local application of 

Punica granatum seed oil on bone 
healing. Int J Biomater. 
2022;2022:426658. 

18. Dantas TS, de Barros Silva PG, 
Verde MEQL, Júnior ALR, Cunha 
MS, Mota MRL, et al. Role of 
inflammatory markers in the 
prognosis of oral squamous cell 
carcinoma. Asian Pac J Cancer 
Prev. 2019;20(12):3635. 

19. Takahiro T, Sushil K, Rohan N, 
Vahid A, Guillaume T, Hwan C, et 
al. Quantitative multiplex 
immunohistochemistry reveals 
myeloid-inflamed tumor immune 
complexity associated with poor 
prognosis. Cell Rep. 2017;19:203–
17. 

20. Rizzardi A, Johnson A, Vogel R, 
Pambuccian S, Henriksen J, Skubitz 
A, et al. Quantitative comparison 
of immunohistochemical staining 
measured by digital image analysis 
versus pathologist visual scoring. 
Diagn Pathol. 2012;7:42. 

21. Al-Ghaban NM, Jasem GH. 
Histomorphometric evaluation of 
the effects of local application of 
red clover oil (Trifolium pratense) 
on bone healing in rats. J Bagh Coll 
Dent. 2020;32(2):26–31. 

22. Abed A, Al-Ghaban NMH. 
Acceleration of ulcer healing by 
local application of myrrh oil: An 
experimental study. Al Anbar Med 
J. 2023. 
doi:10.33091/amj.2023.140046.11
31. 

23. Elsherif NA, Abdelhamid MM, 
Taha A. Histopathological 
Evaluation of Cancer Tendency in 



Localiza(on of E-cadherin and Vimen(n in Mucosal Ulcer Healing Treated by Vi(s Vinifera Seeds Oil in Rat 
Model 

Vol 13 No 1 (2025)    DOI 10.5195/d3000.2025.847 

 h#p://den*stry3000.pi#.edu 

the Buccal Mucosa of Aged Albino 
Rats (Histological and 
Immunohistochemical Study). Ain 
Shams Dental Journal. 2023 Dec 
1;32(4):37-48. 

24. Kamil N, Al-Ghaban N. 
Evaluation of effect of local 
exogenous application of myrrh oil 
on healing of wound incisions of 
facial skin. J Bagh Coll Dent. 
2019;31. 
doi:10.26477/jbcd.v31i4.2724. 

25. Cavalcante GM, Sousa de Paula 
RJ, Souza LP, et al. Experimental 
model of traumatic ulcer in the 
cheek mucosa of rats. Acta Cir 
Bras. 2011;26(3):227–34. 
doi:10.1590/s0102-
86502011000300012. 

26. Youssry G, Sabet NE, Abbas IT, 
Negm IM, Al Boghdady DM. 
Evaluation of Nasolabial Angle 
Changes after Dermal Fillers 
Injection of Skeletal Class III 
Orthodontically Treated Females. 
Ain Shams Dental Journal. 2023 
Dec 1;32(4):1-5.. 

27. Burandt E, Lübbersmeyer F, 
Gorbokon N, et al. E-Cadherin 
expression in human tumors: a 
tissue microarray study on 10,851 
tumors. Biomark Res. 
2021;9(1):44. doi:10.1186/s40364-
021-00299-4. 

28. Sridevi U, Jain A, Nagalami V, 
Kumar UV, Goyal S. Expression of 
E-cadherin in normal oral mucosa, 
in oral precancerous lesions and in 
oral carcinomas. Eur J Dent. 
2015;9:364–72. 

29. Ostrowska-Podhorodecka Z, 
Ding I, Norouzi M, McCulloch CA. 
Impact of vimentin on regulation 
of cell signaling and matrix 
remodeling. Front Cell Dev Biol. 
2022;10:869069. 
doi:10.3389/fcell.2022.869069. 

30. Kuwahara H, Tosa M, Egawa S, 
Murakami M, Mohammad G, 
Ogawa R. Examination of epithelial 
mesenchymal transition in keloid 
tissues and possibility of keloid 
therapy target. Plast Reconstr Surg 
Glob Open. 2016;4(11):e1138. 
doi:10.1097/GOX.0000000000001
138. 

31. Chai J, Norng M, Modak C, et 
al. CCN1 induces a reversible 
epithelial–mesenchymal transition 
in gastric epithelial cells. Lab 
Invest. 2010;90:1140–51. 
doi:10.1038/labinvest.2010.101. 

32. Sawant S, Vaidya M, Chaukar 
D, Alam H, Dmello C, Gangadaran 
P, et al. Clinical significance of 
aberrant vimentin expression in 
oral premalignant lesions and 
carcinomas. Oral Dis. 
2013;20(5):453–65. 
doi:10.1111/odi.1215. 

33. Baum B, Settleman J, Quinlan 
MP. Transitions between epithelial 
and mesenchymal states in 
development and disease. Semin 
Cell Dev Biol. 2008;19:294–308. 

34. Lee JM, Dedhar S, Kalluri R, 
Thompson EW. The epithelial–
mesenchymal transition: New 
insights in signaling, development, 
and disease. J Cell Biol. 
2006;172:973–81. 

35. Tian MY, Li Y. The expression 
of E-cadherin and vimentin in non-
small cell lung cancer and their 
correlation with epithelial–
mesenchymal transition. J Biosci 
Med. 2018;6:1–8. 

36. Yuksel H, Ocalan M, Yilmaz O. 
E-cadherin: An important 
functional molecule at respiratory 
barrier between defense and 
dysfunction. Front Physiol. 
2021;12:720227. 
doi:10.3389/fphys.2021.720227.