Exploring the Role of Vitamin D, Vitamin D-Dependent Proteins, and Vitamin D Receptor Gene Variation in Lung Cancer Risk.

Lung cancer has an unfavorable prognosis with a rate of low overall survival, caused by the difficulty of diagnosis in the early stages and resistance to therapy. In recent years, there have been new therapies that use specific molecular targets and are effective in increasing the survival chances of advanced cancer. Therefore, it is necessary to find more specific biomarkers that can identify early changes in carcinogenesis and allow the earliest possible treatment. Vitamin D (VD) plays an important role in immunity and carcinogenesis. Furthermore, the vitamin D receptor (VDR) regulates the expression of various genes involved in the physiological functions of the human organism. The genes encoding the VDR are extremely polymorphic and vary greatly between human populations. To date, there are significant associations between VDR polymorphism and several types of cancer, but the data on the involvement of VDR polymorphism in lung cancer are still conflicting. Therefore, in this review, our aim was to investigate the relationship between VDR single-nucleotide polymorphisms in humans and the degree of risk for developing lung cancer. The studies showcased different gene polymorphisms to be associated with an increased risk of lung cancer: TaqI, ApaI, BsmI, FokI, and Cdx2. In addition, there is a strong positive correlation between VD deficiency and lung cancer development. Still, due to a lack of awareness, the assessment of VD status and VDR polymorphism is rarely considered for the prediction of lung cancer evolution and their clinical applicability, despite the fact that studies have shown the highest risk for lung cancer given by TaqI gene polymorphisms and that VDR polymorphisms are associated with more aggressive cancer evolution.

Human Periapical Odontogenic Granulomas: Aspects of Microvessel Density (MVD), Heterogeneity of Blood Vessels and Mast Cells Density (MCD).

Periapical odontogenic granulomas are among the most encountered pathology that involve the alveolar bone, with severe consequences such as bone resorption, the presence of inflammatory infiltrate and the formation of abnormal vascularization. The present study aimed to quantify the existence of the microvessel density (MVD), mast cell density (MCD) and heterogeneity of the encountered blood vessels. A total of 37 patients diagnosed with odontogenic periapical granulomas were included, and the gender distribution, age and localization of the pathological lesions was assessed. After the surgical removal of the periapical odontogenic granuloma, the collected tissue was fixed in 10% buffered formalin. Primary processing, morphological analysis and immunohistochemical staining was performed in order to characterize the altered tissue. The results outlined the presence of a high number of mast cells, especially in the area of the inflamed tissue; the high heterogeneity of the blood vessels; and increased MVD with positive CD34. The conclusions of the study focus on the key role of the mast cells and their implication in the initiation and development of the angiogenesis process, triggering the inflammatory response of the host. Nevertheless, periapical odontogenic granulomas develop as an inflammatory response to the interaction between the host's immune system and microbial invasion.

Associated Bacterial Coinfections in COVID-19-Positive Patients.

Background and Objectives: The aim of this study was to identify specific rhino- and oropharyngeal microbiological pathogens as well as associated comorbidities that favor SARS-CoV-2 infection and corelate them. Materials and Methods: This prospective clinical study enrolled 61 patients (28 COVID-19-positive and 33 controls) who were tested for other comorbidities and co-existence of associated oral pathogenic microbiota. Results: A total of 247 bacterial isolates were identified in the bacterial cultures in both groups. Viral hepatitis type A was more prevalent in the COVID-19-positive group (p = 0.026), as was the presence of oral candidiasis (p = 0.006). In the control group, a moderate direct relationship was observed between the Beta hemolytic streptococcus group G and dermatitis, and strong direct relationships were observed between the Beta hemolytic streptococcus group G and external otitis, Streptococcus pyogenes and dental alveolitis, and Streptococcus pyogenes and chronic lymphocytic leukemia. In the test group, strong direct relationships were observed between Hemophilus influenzae and pulmonary thromboembolism; Staphylococcus aureus and autoimmune thyroiditis; post-viral immunosuppression, chronic coronary syndrome, and hypernatremia; Beta hemolytic streptococcus group C and rheumatoid polyneuropathy; Beta hemolytic streptococcus group G and hyperkalemia, hypothyroidism, secondary anemia, and splenomegaly; and active oral candidiasis and SARS-CoV-2 viral pneumonia. The following relationships were strong, but inverse: Beta hemolytic streptococcus group G and acute respiratory failure, and active oral candidiasis and SARS-CoV-2 viral bronchopneumonia. Conclusions: Briefly, COVID-19-positive patients have the predisposition to build up associated comorbidities and coinfections, which can be the expression of the immune burden that this virus generates to the host.

Mesenchymal Stem Cells Derived from Human Periapical Cysts and Their Implications in Regenerative Medicine.

Mesenchymal stem cells currently play an important role in the tissue engineering field in developing new regenerative approaches. The oral cavity is a rich source of mesenchymal stem cells, and introducing the use of dental stem cells, characterized by a multilineage differentiation potential, immunomodulatory activity and repair capacity, offers a good perspective for clinical dentistry. Human periapical cyst mesenchymal stem cells (hPCy-MSCs) represent a new category of dental stem cells, being collected from pathological tissue and exhibiting MSCs-like properties. As studies have described, these new identified cells possess the same characteristics as those described in MSCs, exhibiting plasticity, a high proliferation rate and the potential to differentiate into osteogenic, adipogenic and neural lineages. Reusing the biological tissue that is considered pathologic offers a new perspective for the development of further clinical applications. The identification and characterization of MSCs in the human periapical cysts allows for a better understanding of the molecular interactions, the potential healing capacity and the mechanisms of inducing the local osteogenic process, integrated in the microenvironment. Although their involvement in regenerative medicine research is recent, they exhibit important properties that refer them for the development of clinical applications in dentistry.

Retromolar Triangle Anesthesia Technique: A Feasible Alternative to Classic?

Anesthetic techniques play an important role in the outcome of the therapeutic procedures in dentistry. Although inferior alveolar nerve block (IANB) anesthesia is currently the most often used, there are situations that imply the need of an alternative anesthesia technique to overcome the potential risks and complications. The aim of the study was to evaluate the efficacy of the retromolar triangle anesthesia technique in achieving the desired nerve block, while evaluating the duration of the anesthesia for the included cases. METHODS: The present prospective study included 50 subjects that had indication of inferior molar extraction. The performed anesthesia technique for these cases was the retromolar triangle approach, and the analyzed parameters for evaluating the efficacy of this anesthesia technique were the positive nerve block of the branches involved in the area (inferior alveolar, buccal, and lingual nerves) and the duration of the anesthesia. RESULTS: The efficiency of the retromolar triangle anesthesia technique was positive in 64% of the cases for the inferior alveolar nerve, 46% of the cases for the lingual nerve, and 22% of the cases for the buccal nerve. The duration of the anesthesia revealed a mean value of 72.4 min, suggesting that the duration is an essential factor in its effectiveness. CONCLUSIONS: Retromolar triangle anesthesia can be a viable option for clinicians, offering a simple and easy approach for the management of clinical cases.

Impact of Treatment on Systemic Immune-Inflammatory Index and Other Inflammatory Markers in Odontogenic Cervicofacial Phlegmon Cases: A Retrospective Study.

Cervicofacial odontogenic infections can have an aggressive evolution with life-threatening complications. Management in many cases can be a challenge for clinicians, implying an extra focus on individual inflammatory parameters. The aim of this study is to evaluate the evolution of inflammatory markers for the included diagnosed odontogenic cervicofacial phlegmon cases at the moment of hospitalization and after receiving surgical and pharmaceutical treatment. MATERIALS AND METHODS: A total of 39 patients diagnosed with odontogenic cervicofacial phlegmons that were admitted to the Maxillofacial Surgery Department of the Emergency Hospital from Timisoara were included in the study. The main focus was the parameters represented by the systemic immune-inflammatory index (SII) based on neutrophil, platelet, and lymphocytes count; the neutrophil-lymphocyte ratio (NLR); C-reactive protein level (CRP); and white blood cell count (WBC) before and after the treatment as potential prognosis factors. RESULTS: The results of the study after analyzing the included parameters revealed a significant difference between the calculated values of the SII, NLR, CRP, and WBC at admission and at time of discharge, being directly influenced by the treatment. CONCLUSIONS: SII, NLR, CRP, and WBC dynamic changes in severe cervicofacial odontogenic infections can be influenced by receiving accurate surgical and pharmacological treatment, with the potential to become future severity prognosis indexes.

Circulating miRNA as a Biomarker in Oral Cancer Liquid Biopsy.

Oral cancer is currently challenging the healthcare system, with a high incidence among the population and a poor survival rate. One of the main focuses related to this malignancy is the urge to implement a viable approach for improving its early diagnosis. By introducing the use of liquid biopsy and the identification of potential biomarkers, aiming for a noninvasive approach, new advancements offer promising perspectives in the diagnosis of oral cancer. The present review discusses the potential of circulating miRNAs as oral cancer biomarkers identified in body fluids such as serum, plasma, and saliva samples of oral cancer patients. Existing results reveal an important implication of different miRNA expressions involved in the initiation, development, progression, and metastasis rate of oral malignancy. Liquid biomarkers can play a crucial role in the development of the concept of personalized medicine, providing a wide range of clinical applications and future targeted therapies.

Heterogeneity of Blood Vessels and Assessment of Microvessel Density-MVD in Gingivitis.

Gingivitis is a very common oral disease highly prevalent in adults that, if left untreated, can progress to periodontitis. It involves a complex and slow interaction between the host response and the oral microbiome represented by the dental plaque. The inflammation of the gingiva is associated with the activation of pathological angiogenesis and the existence of a high number of newly formed blood vessels quantified as microvessel density (MVD). The present study includes a number of 51 gingival biopsies from patients with different gingival indexes (GI): GI = 0, n = 12; GI = 1, n = 15; GI = 2, n = 16; and GI = 3, n = 8, processed and stained with the routine hematoxylin-eosin method. The inflammatory infiltrate was scored, the blood vessels were detected with anti-CD34 antibody, and MVD was determined. Inflammatory changes were observed in 39 of the 51 cases included in our study. CD34 + vessels with normal morphological appearance were observed in all 12 cases of health gingiva. In cases of inflammatory lesions, the morphology of the blood vessels showed changes with the evolution of gingival lesions. In severe inflammation, a particular aspect was observed in the vessels, such as the presence of the phenomenon of intussusception. MVD increases with the severity of gingival lesions, with the highest density being observed in severe inflammation.

Complementarity of Photo-Biomodulation, Surgical Treatment, and Antibiotherapy for Medication-Related Osteonecrosis of the Jaws (MRONJ).

Background and Objectives: Antiresorptive or anti-angiogenic agents may induce medication-related osteonecrosis of the jaws (MRONJ), which represents a challenge for clinicians. The aim of this study is to design and apply a composed and stage-approach therapy combining antibiotherapy, surgical treatment, and photo-biomodulation (PBM) for the prevention or treatment of MRONJ lesions. Materials and Methods: The proposed treatment protocol was carried out in the Department of Oral & Maxillofacial Surgery of the "Victor Babes" University of Medicine and Farmacy of Timisoara, in 2018-2020. A total of 241 patients who were previously exposed to antiresorptive or anti-angiogenic therapy, as well as patients already diagnosed with MRONJ at different stages of the disease were treated. A preventive protocol was applied for patients in an "at risk" stage. Patients in more advanced stages received a complex treatment. Results: The healing proved to be complete, with spontaneous bone coverage in all the n = 84 cases placed in an "at risk" stage. For the n = 49 patients belonging to stage 0, pain reductions and decreases of mucosal inflammations were also obtained in all cases. For the n = 108 patients proposed for surgery (i.e., in stages 1, 2, or 3 of MRONJ), a total healing rate of 91.66% was obtained after the first surgery, while considering the downscaling to stage 1 as a treatment "success", only one "failure" was reported. This brings the overall "success" rate to 96.68% for a complete healing, and to 99.59% when downscaling to stage 1 is included in the healing rate. Conclusions: Therefore, the clinical outcome of the present study indicates that patients with MRONJ in almost all stages of the disease can benefit from such a proposed association of methods, with superior clinical results compared to classical therapies.

The Challenges of OSCC Diagnosis: Salivary Cytokines as Potential Biomarkers.

Fast, economic, and noninvasive, molecular analysis of saliva has the potential to become a diagnostic tool of reference for several local and systemic diseases, oral cancer included. The diagnosis of Oral Squamous Cell Carcinoma (OSCC) can be performed using high specificity and sensibility biomarkers that can be encountered in the biological fluids. Recent advances in salivary proteomics have underlined the potential use of salivary biomarkers as early diagnosis screening tools for oral neoplasia. In this respect, over 100 salivary molecules have been described and proposed as oral cancer biomarkers, out of which cytokines are among the most promising. Besides being directly involved in inflammation and immune response, the role of salivary cytokines in tumor growth and progression linked them to the incidence of oral malignant lesions. This review summarizes the existing studies based on the use of salivary cytokines as potential oral cancer biomarkers, their involvement in the malignant process based on their type, and ther influence upon prognostic and metastatic rates.

Oral cancer histopathological subtypes in association with risk factors: a 5-year retrospective study.

BACKGROUND: Oral cancer is a worldwide public health problem, being the sixth most common neoplasm. The high mortality rate of this type of cancer is due to a delayed diagnosis, a fast evolution and metastasis, no primary symptomatology, the multitude of risk factors and the lack of awareness among the population concerning oral malignancy. AIM: The aim of this 5-year retrospective study was to evaluate the incidence of oral cancer patients in the Clinic of Maxillo-Facial Surgery, Emergency County Hospital, Timisoara, Romania and quantify the histopathological (HP) subtypes, localization, age, gender, tumor staging and differentiation, positive loco-regional lymph nodes and risk factors. PATIENTS, MATERIALS AND METHODS: A number of 129 patients diagnosed with oral cancer were included in the study and their medical records were analyzed. A statistical analysis was performed that included the variables gender, age, tumor staging, differentiation grade, HP subtype, lymph nodes, localization, and risk factors. RESULTS: Our results outlined a high prevalence of oral cancer among males (65.9%), squamous cell carcinoma (SCC) being the most common HP subtype. Tumor staging revealed the fact that the majority of were T3 and T4 tumors with dissemination in the loco-regional lymph nodes. In 52% of the cases, tobacco was identified as a risk factor, and the association of tobacco and alcohol was present in 28.3% of the cases. CONCLUSIONS: The early diagnosis is crucial for the improvement of oral cancer survival rate. The oral cavity is permanently exposed to carcinogenic substances that associated with other risk factors have an influence upon the incidence of oral malignancies.

Contribution of the cyto-histopathological diagnosis and ultrastructural parameters to the evaluation of maxillary cysts - a 10-year multidisciplinary approach.

Diagnostic and treatment plans in cystic jawbone tumors are often difficult to address. The etiopathogenic links involved in cell-matrix differentiation disorders are complex. Quantification of the inflammatory process in the evolution of cystic odontogenic lesions highlights a particular reactivity of the host, especially age-dependent and the endodontic-periodontal space interrelation, drawing attention to the difficulties of etiopathogenic, evolution, prognostic and treatment of these lesions. Difficulties in histopathological (HP) diagnosis are reported by the lack of morphofunctional integration of dental tissues, both topographically and evolutionarily, especially when odontogenic epithelial remains in the cystic wall, reactive bone condition, appearance and condition of the reactive epithelium are overlooked. In this study, we developed an interdisciplinary approach for the dynamics of tissue morphology found in the walls of maxillary cysts. Failure to recognize the tissues that form the cystic lesion leads to misinterpretations of pathology and to the wrong classification in the group of maxillary cysts. We analyzed by different techniques 564 biopsy fragments from maxillary cystic lesions, most of which are clinically classified as inflammatory or odontogenic ones. From our experience, we reevaluated the lesions with cystic changes and completed the diagnosis in 10-12% of cases. The most common maxillary cystic lesion encountered by us was the root cyst, an inflammatory dental cyst, which has been over diagnosed clinically, radiologically and histopathologically. Recognition and selection of embryonic remnants from odontogenesis is crucial for the HP diagnosis of maxillary cysts, allowing the clinician to monitor treatment or to develop evolutionary-prognostic perspectives of odontogenic cystic lesions.

Oral Bone Tissue Engineering: Advanced Biomaterials for Cell Adhesion, Proliferation and Differentiation.

The advancements made in biomaterials have an important impact on oral tissue engineering, especially on the bone regeneration process. Currently known as the gold standard in bone regeneration, grafting procedures can sometimes be successfully replaced by a biomaterial scaffold with proper characteristics. Whether natural or synthetic polymers, biomaterials can serve as potential scaffolds with major influences on cell adhesion, proliferation and differentiation. Continuous research has enabled the development of scaffolds that can be specifically designed to replace the targeted tissue through changes in their surface characteristics and the addition of growth factors and biomolecules. The progress in tissue engineering is incontestable and research shows promising contributions to the further development of this field. The present review aims to outline the progress in oral tissue engineering, the advantages of biomaterial scaffolds, their direct implication in the osteogenic process and future research directions.

A New Approach for the Diagnosis of Systemic and Oral Diseases Based on Salivary Biomolecules.

Early diagnosis represents the target of contemporary medicine and has an important role in the prognosis and further treatment. Saliva is a biofluid that generated a high interest among researchers due to its multiple advantages over other body fluids. The multitude of components that can act as biomarkers influenced the existing technologies to develop protocols that could allow saliva to become the new noninvasive diagnostic method. Saliva as a diagnostic tool can bring substantial addition to the diagnostic armamentarium, providing important information about oral and general health. The diagnostic applications of saliva extended and had a rapid evolution due to the advancement in salivaomics. The present review summarizes the latest researches in saliva-related studies and explores the information and correlations that saliva can offer regarding the systemic and oral diseases, highlighting its great potential of diagnosis. It is expected that in the future specific guidelines and results regarding the salivary diagnostics are to be available, together with high-sensitivity and specificity tests for multiple systemic and oral diseases.

Craniofacial morphology and its relation to the eruption pattern of permanent teeth in the supporting zone of the dentition in a group of Romanian children in Timisoara.

The purpose of this study is to determine the cephalic and facial morphological typology in prepubertal children from Timisoara (Romania) and to develop a population-specific reference for the dental eruption of permanent teeth in the supporting zone of the dentition, in relation to the facial morphological typology. Using cephalic and facial indexes in a group of 234 preadolescents with mixed dentition, we quantified morphological associations between cephalic and facial types, using a cross-sectional design. The prepubertal children in Timisoara have a dominant mesoprosopic facial type and mesocephalic type. For supporting zone of the dentition, the presence of permanent teeth, the canine, the first premolar and the second premolar was recorded, for all four quadrants. Dental eruption in the supporting zone of the dentition has particularities depending on population group, gender, dental arch, but also facial type. From the data of this study, the following patterns of eruption, specific to each facial type, have resulted: for leptoprosopic facial type - first upper premolar (UP1), second upper premolar (UP2), upper canine (UC)∕first lower premolar (LP1), lower canine (LC), second lower premolar (LP2); for mesoprosopic facial type - UP1, UP2, UC∕LC, LP1, LP2; and for euryprosopic facial type - UP1, UP2, UC∕LC, LP1, LP2. The leptoprosopic and euryprosopic facial types have a delayed and accelerated eruption compared to the mesoprosopic facial type. The euryprosopic facial type has more intense mandibular eruption. The leptoprosopic facial type registers the largest percentage of children requiring orthodontic treatment. Monitoring the sequence of eruption of the permanent teeth is very important to ensure the balanced development of the dental occlusion, mandible and facies as a whole.