The Effect of Acetyl-L-Carnitine (ALCAR) on Peripheral Nerve Regeneration in Animal Models: A Systematic Review.

Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness, autonomic symptoms, and debilitating pain syndrome with a wide range of clinical signs. Acetyl-L-Carnitine (ALCAR) is a biological compound with essential roles in mitochondrial oxidative metabolism and anti-oxidant effects that protects mitochondria from oxidative damage and inhibits apoptosis caused by mitochondrial damage. This study is a systematic review and meta-analysis of the effects of ALCAR on peripheral nerve injuries. This review examines studies on treating traumatic peripheral neuropathies in which ALCAR is administered to rats with sciatic nerve injury with an appropriate control group. The articles were divided based on the mode of ALCAR administration. If one method was used in more than one article, their results were entered in the "Revman5.4" software and were meta-analyzed. Studies were selected from 1994 to 2018 on rats with varying physical injuries to their sciatic nerves. In one study, ALCAR was provided to rats in their drinking water, while in other studies, ALCAR was injected intra-peritoneally. Different mechanisms of ALCAR actions have been suggested in this study, but the underpinnings of the neuroprotective effects of ALCAR are still unclear. Further studies are mandatory to clarify the actual mechanisms of the neuroprotective activity of ALCAR. Based on the results of existing studies, ALCAR effectively increases the tolerance threshold of thermal and mechanical stimuli, reduces latency, and reduces apoptosis; finally, adjusting the dose and duration of administration may increase the dose and duration axon diameter.

Assessment of the association of OCT3/4 with GLUT1 and CD105 in oral squamous cell carcinoma using dual immunohistochemistry.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer affecting the oral and maxillofacial region. This study aimed to investigate the role of cancer stem cells (CSCs) in angiogenesis and hypoxic response in OSCC. METHODS: This retrospective observational study evaluated 56 cases of OSCC using dual immunohistochemistry. Octamer-binding transcription factor 3/4 (OCT3/4) marker was used to evaluate CSC activity. Glucose transporter 1 (GLUT1) marker was used to evaluate the hypoxic response and angiogenesis, while endoglin (CD105) was used to evaluate the late stage of angiogenesis and blood vessel formation. RESULTS: Co-expression of OCT3/4 and GLUT1 was noted in 11 of 12 patients with grade III OSCC. However, we did not observe co-expression of these markers in 13 of 22 patients with grade I OSCC. Although we observed a significant correlation between co-expression of GLUT1 and OCT3/4 and tumor grade, there was no significant correlation between co-expression of OCT3/4 and CD105 and different grades of OSCC. CONCLUSIONS: CSCs could play important roles in the initial stages of hypoxic response and angiogenesis. Our result reported that in higher grades of OSCC, GLUT1 as a first response to hypoxic situations might be a result of CSCs. Further studies are required to discover other biomarkers, their roles, and associated pathways of CSCs in OSCC.

The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma.

BACKGROUND: Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. METHODS: A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. RESULTS: A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. DISCUSSION: The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

The effect of aflibercept and arsenic trioxide on the proliferation, migration and apoptosis of oral squamous cell carcinoma in vitro.

Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs, especially arsenic trioxide, on oral squamous cell carcinoma (OCC). We used three OCC lines as a model to show the effect of these drugs on the genetically complex disease and investigate its targeted therapy. In this study, three human OCC cell lines were used from different patients. We treated cell lines with both medications to detect the effect and relevant molecular basis. First, methyl thiazolyl tetrazolium (MTT) assay was performed to detect the cytotoxicity effect and cell growth. Second, flow cytometry, gene and protein expression were performed to evaluate the anti-angiogenic effect on OCC lines. Next apoptosis was analyzed by flow cytometry. Finally, clonogenesis capacity and cell migration were assessed by colony formation assay and wound healing, respectively. Aflibercept had no cytotoxic effect on the three OCC cell lines but decreased cell growth rate. Arsenic trioxide had a significant cytotoxic effect on three cell lines. Our results demonstrated that both drugs significantly decreased endoglin, VEGFA, and VEGFB expression. In addition, Migration and colony formation assays confirmed that these drugs have significant anti-proliferative and anti-migration effect on oral carcinoma cells. These results revealed that both medications might be a potential drug for the management of oral cancer patients.

Evaluation of circulating serum 3 types of microRNA as biomarkers of oral squamous cell carcinoma; A pilot study.

INTRODUCTION: The microRNAs are molecules which have important biologic role and play key point in cancers. The aim of present study was to determine the miR-21, miR-24, and miR-29a expression in serum of patients with oral squamous cell carcinoma. MATERIALS AND METHODS: Blood samples were obtained from 40 patients (20 in cases and 20 in control group) to determine the miR-21, miR-24, and miR-29a expressions by using real-time PCR and ΔCT. RESULTS: Mean miR-29a was -2.28 ± 2.15 and 5.61 ± 2.38 in case and control groups, respectively. The miR-21 was 6.90 ± 3.86 and -0.88 ± 2.31 in case and control groups, respectively. According to the results, miR-24 was 2.13 ± 2.89 and -0.35 ± 2.44 in case and control, respectively. A significant difference was observed on miR-21, miR-24, and miR-29a between two groups (P < .05). The results obtained by t test showed miR-21 and miR-24 were higher and miR-29a was lower in plasma of oral squamous cell carcinoma patients and this differences were significant (P < .05). CONCLUSION: These results suggested miR-21, miR-24, and miR-29a in serum of patients with oral squamous cell carcinoma comparing with normal group can be used as potent markers for carcinoma detection and also may be a potentially therapeutic approach in the future. More longitudinal studies with larger samples are necessary to confirm these findings.

Benign Cementoblastoma Involving Deciduous and Permanent Mandibular Molars: A Case Report.

Cementoblastomas are rare benign odontogenic tumors. Diagnosis of these lesions must be made by an association of clinical, radiographic, and histopathological findings. Cementoblastomas rarely occur in both primary and permanent dentitions. We describe the sixth case of cementoblastoma in the literature with the involvement of both deciduous and permanent teeth. The aim of this case report is to present the clinicoradiopathologic features of a cementoblastoma in a 4.5-year-old boy with an unusual recurrence. The first clinical and radiographic features appeared on the deciduous mandibular second molar. The second lesion occurred 1 year after treatment at 5.5 years old, involving the permanent mandibular first molar, and a subsequent lesion was seen at age 8 years in the edentulous region of the extracted mandibular first molar. After the last surgery, there was no recurrence of the lesion at 6 months' follow-up. Follow-ups of patients with cementoblastomas are highly recommended for an early detection of recurrences.

Human Papillomavirus-Associated Oral Epithelial Dysplasia: A Practical Approach to Make the Diagnosis.

Background: High-risk Human Papillomavirus (HPV) genotypes are found in malignant oral epithelial lesions, and HPV infection is proposed as a risk factor for initiating Squamous cell carcinoma (SCC) in the head and neck region. This study suggests a practical approach to detect HPV in HPV-associated oral epithelial dysplasia (HAOED). Methods: Fifty-four oral epithelial dysplasia specimens were examined, comprising twenty-seven cases diagnosed with high-grade dysplasia and twenty-seven cases diagnosed with low-grade dysplasia using a binary grading system. To assess the cases for HPV, the specimens were examined for p16 protein using an immunohistochemical (IHC) study, and then, the Chromatin In Situ Hybridization (CISH) test was performed for all positive cases. Chromatin Immunoprecipitation-Polymerase Chain Reaction (ChIP-PCR) was performed on CISH-positive specimens to assess the outcome. This cross-sectional study was conducted in 2020 at Tehran University of Medical Science. SPSS software version 22.0 was used to perform the Chi square or Fisher's exact test to examine the relationship between variables (statistically significant level P<0.05). Results: The expression of p16 protein was not associated with the severity of epithelial dysplasia (81.5% in low-grade and 59.2% in high-grade cases) (P=0.16). Moreover, according to the CISH test result, 9.25% of all specimens were positive (P>0.99), and in the nine cases, undergone the ChIP-PCR study, two cases (22.2%) showed positivity for HPV-16, while one case (11.1%) demonstrated positivity for HPV-51. Conclusion: Regarding HAOED, here, we proposed a step-by-step combination approach using different diagnostic methods, including IHC for p16 protein, CISH, and ChIP-PCR based on a complementary algorithm.

Primordial Odontogenic Tumor; Archival Review of 19380 Cases in a 55-Year Retrospective Study.

BACKGROUND AND OBJECTIVE: Primordial odontogenic tumor is a rare odontogenic tumor reported for the first time in 2014. It was included in the latest edition of World Health Organization classification of Head and Neck Tumors as a new benign mixed epithelial-mesenchymal neoplasm. To date, 26 cases has been reported in literature. The aim of this study was to determine the possible presence of primordial odontogenic tumor in the previously diagnosed cases with myxoid stroma. MATERIALS AND METHODS: This study was a retrospective descriptive study that was concluded in Oral and Maxillofacial Pathology Department, School of Dentistry, Tehran University of Medical Sciences. We reviewed all 19,380 cases from 19,66 to find the lesions with myxoid stroma which were in differential diagnosis with primordial odontogenic tumor. These cases should be associated with an impacted or unerupted tooth and belong to the patients under 20 years old. RESULTS: We find 503 pericoronal lesions with myxoid stroma. Three cases were isolated after recut and reevaluation for finding fulfill histologic features. After immunohistochemical analysis, we find a new case of developing primordial odontogenic tumor associated with odontoma. DISCUSSION: Primordial odontogenic tumor a recently described odontogenic tumor has a well-defined clinicopathological and immunohistochemical profile and should be differentiated from the others pericoronal lesions. It is the first time that this archival review has been done to find probable cases of primordial odontogenic tumor.

Fibrous dysplasia associated with peripheral giant cell granoluma in maxilla in a young patient, a case report of rare hybrid lesion.

Benign fibro-osseous lesions are a diverse range of entities that have distinct clinical and radiographic features. They can occur as solitary lesions or concomitant with other pathologies as hybrid lesions. Fibrous dysplasia (FD) accompanied by central giant cell granuloma (CGCG), peripheral giant cell granuloma (PGCG) or peripheral ossifying fibroma (POF) as hybrid lesions, is reported very rarely in the literature. Although we were unable to find any reports of FD with PGCG as a hybrid lesion. Fibro-osseous lesions have certain histopathological features in common with PGCG including multinucleated giant cells. Here we report a 28 year old female with a painless, slow growing and pedunculated swelling of the maxilla for 18 months. Differential diagnosis consisted of FD, cemento-ossifying fibroma (COF), chondrosarcoma and probable PGCG considering radiographic and clinical investigations. Histopathologic findings revealed PGCG and FD as a hybrid lesion. The combination of PGCG and FD has not been reported in the literature so far.

Solitary amyloid tumor of the palate: A case report and literature review.

Amyloidosis is often caused by the abnormal extracellular accumulation of amyloid in organs and tissues. This condition, affecting the head and neck region, is typically localized, and may also involve the oral cavity, particularly the tongue and buccal mucosa. As a solitary manifestation, the localized amyloidosis occurring intraosseous is highly infrequent. In addition, localized amyloidosis has a great rate of recurrence. In this paper, a 50-year-old female patient with the chief complaint of pain in the anterior of the maxilla is reported. According to clinical examination, no significant pathologic lesion was seen. The radiographic image showed a radiolucent lesion around teeth four and five. The treatment of choice for the patient was an excisional biopsy. As amyloidosis diagnosis is clinically challenging, biopsy and histologic examination of lesions are necessary in this regard. Accordingly, it is concluded that long-term follow-up is mandatory in case of localized amyloidosis because late recurrence can occur in some cases.

Mucoepidermoid carcinoma of the palate in a patient with a history of neuroblastoma: A case report and a review of the literature.

Secondary neoplasms were reported as one of the complicated complications of childhood cancer treatment. Salivary gland carcinoma is rare, and mucoepidermoid carcinoma (MEC) is the most prevalent subtype. Secondary neoplasms following neuroblastoma are not often described due to poor long-term survival. The exact cause of these tumors in children, and adults is not clearly known, but they are often observed after head, and neck radiotherapy and mainly involve main salivary glands, especially the parotid. Hence, we report a case of MEC with telangiectasia in the salivary glands of a 20-year-old girl with complaint of a palatal swelling who was treated with chemotherapy (etoposide, G-CSF, cyclophosphamide) without radiotherapy since childhood (18 months) in terms of neuroblastoma. Based on our knowledge, only three cases of MEC following neuroblastoma have been reported before, all of which involved the major salivary glands. Survivors of primary neoplasms who were treated are at risk of secondary malignant neoplasms, which usually occur at a long interval from the primary neoplasm (5-15 years), which necessitates long and close follow-up.

High levels of histone H3 K27 acetylation and tri-methylation are associated with shorter survival in oral squamous cell carcinoma patients.

Background: Acetylation and trimethylation of histone H3 lysine 27 (H3K27ac and H3K27me3) generally activate and repress transcription, respectively. Concurrent activation of H3K27ac and H3K27me3 has been reported to correlate with poor prognosis in hepatocellular carcinoma. A high level of H3K27me3 has been shown to be associated with advanced oral squamous cell carcinoma (OSCC) tumour stage, but prognostic impact of H3K27ac level alone/or in combination with H3K27me3 in OSCC patients had not yet been reported. Material and methods: In this study, immunohistochemistry using specific antibodies against H3K27ac and H3K27me3 was performed on a series of 72 OSCC samples to investigate the association between H3K27ac and H3K27me3 levels and OSCC patient's survival. For each mark, the proportion of labelled cells (percentage) and the intensity of the labelling were measured, and a score of percentage x intensity was calculated. Results: A high percentage of H3K27me3 positive cells was significantly associated with survival in univariate and multivariate analyses (logrank p-value < 0.05). Patients with high total scores of H3K27ac and H3K27me3 labelling also showed significantly shorter survival probabilities (logrank p-value < 0.05) compared to patients with low total scores of labelling for these histone posttranslational modifications (PTMs). Conclusion: Our findings suggest that the detection of both H3K27ac and H3k27me3 could help evaluating prognosis in OSCC patients.

Central oral pulse granuloma: a case report of huge mandibular jaw lesion.

Oral pulse granuloma is a rare lesion of the oral cavity with unclear etiology. Some authors believe this lesion is a foreign body reaction to implanted food particles. In the oral cavity, most cases are found in the posterior regions of the mandible. The edentulous mandible was involved in 20 cases with oral pulse granuloma. In these cases, the premolar-molar site was the most common region. Here we present a case of a 70-year-old male with huge unilateral swelling of the mandible on the left side. This paper aims to present a case of oral pulse granuloma with wide extension, detailed clinicohistopathologic features with 2-year follow-up and a short review of reported cases.

A rare case of maxillary osteoblastoma in a 10-month-old infant.

Osteoblastoma (OSB) is an uncommon (3% of benign and 1% of all) primary bone neoplasm with extremely rare occurrence in head and neck, especially the maxillary bone region. OSB of the jaw mainly involves the mandible bone. We report a 10-month-old male who was admitted to the hospital because of a mass in the right maxillary jaw region. Clinicoradiopathologic features of the patient have been described. The histological examinations revealed OSB of the maxillary bone. Total surgical resection of the tumor was performed with 10 months of follow-up and there is no evidence of recurrence. To the best of our knowledge, it is the first report of maxillary OSB in an infant.

Oral focal mucinosis in an adolescent: A rare entity.

Oral focal mucinosis (OFM) is an extremely rare benign lesion of the oral cavity with unknown etiology, considered the oral counterpart of cutaneous focal mucinosis. It occurs mainly in women in the fourth and fifth decades of life. It has no characteristic features, and diagnosis depends on histological evaluation. Its pathogenesis is related to the excessive production of hyaluronic acid by fibroblasts during collagen production, which leads to focal myxoid degeneration. To date, ten documented cases have been reported in the literature in adolescents. This paper reports a rare case of OFM with a narrative review of the available literature.

Combination of Binary System with Ki67 Immunohistochemical Staining: a Reliable Grading Method for Oral Epithelial Dysplasia.

Statement of the Problem: Oral epithelial dysplasia (OED) is a common potentially malignant lesion of oral cavity that should be managed to prevent likely malignant transformation. Purpose: Here, we present a combination of binary grading system with complementary immunohistochemical (IHC) staining for Ki67 biomarker to provide a reproducible OED grading system. Materials and Method: In this cross-sectional study, seventy out of one hundred OED specimens, which were accompanied by IHC stained microscopic slides for Ki67 antigen were evaluated by four independent oral pathologists. Both three-tier and binary grading systems based on WHO microscopic criteria were employed , blindly in a four-step method with at least two-week interval between each observation. Intra- and inter-observational reliability was assessed using Kappa statistical analysis. Results: OED diagnosis based on binary system showed significant intra-observer reliability comparing to three-tier system without biomarker. Moreover, OED diagnosis based on binary system using Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis in three tier system and based on binary system without Ki67 biomarker showed significant inter-observer reliability comparing to diagnosis based on three-tier system without Ki67. Conclusion: Here, we found that application of IHC staining for Ki67 biomarker in binary system might provide a more reliable grading method for oral pathologist form different educational background.

The expression of ACAT1 in oral squamous cell carcinoma and the adjacent pre-tumour tissue.

Background: Altered acetyl CoA acetyltransferase 1 (ACAT1) expression has been reported in diverse cancers. However, the expression of ACAT1 and its prognostic value in oral squamous cell carcinoma (OSCC) has remained unexplored. Materials and methods: In this study, the expression of ACAT1 was analysed by immunohistochemistry (IHC) in 61 OSCC patients and compared between OSCC and adjacent pre-tumour tissue of 21 patients. Results: The expression of ACAT1 in OSCC tumours is heterogeneous between patients. More specifically, 52.38% of the patients show low expression of ACAT1 in both tumour and adjacent pre-tumour tissues, 9.52% of the patients show high expression of ACAT1 in both tumour and adjacent pre-tumour, 19.05% of the patients have high expression of ACAT1 in tumour tissue and low expression of ACAT1 in adjacent pre-tumour tissue and another 19.05% of the patients have low expression of ACAT1 in tumour tissue and high expression of ACAT1 in adjacent pre-tumour tissue. Conclusion: Comparison of ACAT1 expression, one of the key enzymes in the ketone body metabolic pathway, divided OSCC patients into two groups: 1) similar expression and 2) different expression of ACAT1 in tumour and adjacent pre-tumour tissue. No significant association between ACAT1 levels and overall survival was observed.

Orthokeratinized odontogenic cyst: Report of eight cases and review of literature regarding its malignant transformation.

Orthokeratinized odontogenic cyst (OOC) is an uncommon odontogenic cyst. It has been categorized as a subtype of odontogenic keratocyst (OKC). In 2005, it was classified as a distinct entity. OOC should be histopathologically differentiated from OKC, which has a higher recurrence rate and lower malignant potential. In addition, OOC should be examined for malignant transformation. The epithelium of odontogenic cysts may rarely show malignant transformation. However, malignant transformation has been reported in inflammatory cysts such as the residual cyst and periapical cyst. The number of carcinomas arising from an OOC is low. This paper describes eight cases of OOC; out of which, two showed the development of squamous cell carcinoma from their epithelial lining.

Conventional osteosarcoma of the mandible: Report of a rare case.

Osteosarcoma of the jaw can be successfully treated by a single aggressive surgical operation with good prognosis. Timely diagnosis, with a complete surgical removal of the tumor with clear margins, can fulfill favorable clinical results.

Mandibular sporadic Burkitt lymphoma in an adult patient: A case report and review of the literature.

Only a minor percent of lymphomas arise in the oral cavity. Although rare, dentists and clinicians should not neglect them as a possible consideration in the differential diagnosis of oral lesions.