Dysregulation of miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p in Oral Squamous Cell Carcinoma: A Potential Biomarkers Panel?

Oral squamous cell carcinoma (OSCC) is considered the sixth most common cancer worldwide. To reduce the high mortality of the disease, sensitive and specific diagnostic and prognostic biomarkers are urgently needed. Non-coding RNA, microRNAs (miRNAs), which are short length non-coding transcripts, or long non-coding RNA (lncRNA) seem to be potential biomarkers, considering that they have an important role in regulation of cell fate being involved in a wide range of biological processes. Literature data emphasized the important role of these transcripts as a biomarker for diagnosis and prognosis in oral squamous cell carcinoma. Therefore, we have evaluated the expression levels of a panel of four miRNAs (miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p) and H19, MALAT1 by quantitative real-time PCR (qRT-PCR) from 33 fresh frozen tissues and 33 normal adjacent tissues. Our date revealed miR-21-5p and miR-93-5p to be upregulated, while miR-200c-3p and miR-205-5p to be downregulated. Regarding the long non-coding RNAs, H19 and MALAT1, were also downregulated. We also investigated the expression of BCL2, which is another important gene correlated to non-coding RNAs investigated by as, and it was also under-expressed. Additional validation step at protein level was done for KI67, TP53 and BCL2. In our patient cohort no correlation with clinical stage and smoking status was observed. The results of the present study indicated the important role of miR-21-5p, miR-93-5p, miR-200c-3p, miR-205-5p and H19 in OSCC. Differential expression of these transcripts at sub-sites, may serve as a diagnostic marker with further elaboration on a larger sample size. Additional studies should be conducted to confirm the results, particularly the interconnection with coding and non-coding genes.

In quest of a new therapeutic approach in COVID-19: the endocannabinoid system.

The SARS-Cov-2 virus caused a high morbidity and mortality rate disease, that is the COVID-19 pandemic. Despite the unprecedented research interest in this field, the lack of specific treatments leads to severe complications in a high number of cases. Current treatment includes antivirals, corticosteroids, immunoglobulins, antimalarials, interleukin-6 inhibitors, anti-GM-CSF, convalescent plasma, immunotherapy, antibiotics, circulation support, oxygen therapy, and circulation support. Due to the limited results, until specific treatments are available, other therapeutic approaches need to be considered. The endocannabinoid system is found in multiple systems within the human body, including the immune system. Its activation can lead to beneficial results such as decreased viral entry, decreased viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-γ. Moreover, endocannabinoid system activation can lead to an increase in anti-inflammatory cytokines, mainly represented by IL-10. Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immunomodulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the 'cytokine storm'. Although the cannabinoid system has many mechanisms to provide certain benefits in the treatment of SARS-CoV-2 infected patients, research in this field is needed for a better understanding of the cannabinoid impact in this situation.

In Vivo Validation of a Nanostructured Electrospun Polycaprolactone Membrane Loaded with Gentamicin and Nano-Hydroxyapatite for the Treatment of Periodontitis.

The aim of this research was to validate the use of a gentamicin (GEN) and nano-hydroxiapatite (nHAP)-loaded polycaprolactone nanostructured membrane (NM) as an innovative, highly efficient, low-cost treatment for periodontitis. We conducted an in vivo study on Wistar rats, in which we induced periodontitis by placing silk ligatures around the first right and left upper molars. The subjects were divided into three groups; the first group received no periodontal treatment, the second group received open flap debridement, and the third group received open flap debridement, together with the positioning of the GEN and nHAP-loaded nanostructured membrane as a treatment. The extent of periodontal regeneration was assessed by the periodontal pocket depth, bleeding on probing, tooth mobility, dental plaque, microbiological analysis, concentration of MMP-8 in saliva, plasma levels of CRP, and histological analysis. The results showed that using open flap debridement with the NM is more efficient, and it significantly reduces the probing depth, extent of bleeding on probing, dental mobility, bacterial plaque, and pathogenic flora. The concentrations of MMP-8 and CRP decrease. The histological analysis demonstrated that NM leads to bone regeneration. Our study indicates that gentamicin and nano-hydroxyapatite embedded in the fiber of the biodegradable membranes might be a promising therapeutic option for periodontitis treatment.

Epigenetic methylation changes: implication as biomarkers in oral and maxillofacial area cancers.

Background/Aim: Squamous cell carcinoma (SCC) is the most frequent cancer of the head and neck area in the oral cavity. Epigenetic alterations in oral and maxillofacial area cancers are urgently needed to be investigated, as the observed changes might have crucial diagnostic value for personalized medicine. Methods: Our study aimed to identify the most frequently hypermethylated tumor suppressor gene promoters in OSCC, followed by correlation analysis with the patients' survival. We evaluated the methylation status of the promoters in a panel of 22 tumor suppressor genes in Romanian (n=9) and Bulgarian (n=12) patient groups suffering from oral and maxillofacial area cancers. The extracted DNA was further digested through EpiTect Methyl II PCR Array System containing methylation-sensitive and methylation-dependent restriction enzymes, followed by specific amplification of the products obtained by qPCR and data analysis using the online platform provided by the producer. Results: Different methylation patterns were observed in the tumor suppressor genes' promoters. Among them, the methylation profile of Cccnd2, Chd1, Cdh13, Cdkn1c, Neurog1, Gstp1, and Runx3 genes further correlated with overall survival rates. Conclusions: Our data emphasize that epigenetic alterations are responsible for the clinical heterogeneity of oral and maxillofacial area cancers and significantly impact on patient survival. Additional investigation on a larger patient cohort should validate these potential biomarkers.

The World of Oral Cancer and Its Risk Factors Viewed from the Aspect of MicroRNA Expression Patterns.

Oral cancer is one of the leading causes of death worldwide, with a reported 5-year survival rate of around 50% after treatment. Epigenetic modifications are considered to have a key role in oral carcinogenesis due to histone modifications, aberrant DNA methylation, and altered expression of miRNAs. MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in cancer development by regulating signaling pathways involved in carcinogenesis. MiRNA deregulation identified in oral cancer has led to the idea of using them as potential biomarkers for early diagnosis, prognosis, and the development of novel therapeutic strategies. In recent years, a key role has been observed for risk factors in preventing and treating this malignancy. The purpose of this review is to summarize the recent knowledge about the altered mechanisms of oral cancer due to risk factors and the role of miRNAs in these mechanisms.

Gradual Drug Release Membranes and Films Used for the Treatment of Periodontal Disease.

Periodontitis is an inflammatory disease that, if not treated, can cause a lot of harm to the oral cavity, to the patients' quality of life, and to the entire community. There is no predictable standardized treatment for periodontitis, but there have been many attempts, using antibiotics, tissue regeneration techniques, dental scaling, or root planning. Due to the limits of the above-mentioned treatment, the future seems to be local drug delivery systems, which could gradually release antibiotics and tissue regeneration inducers at the same time. Local gradual release of antibiotics proved to be more efficient than systemic administration. In this review, we have made a literature search to identify the articles related to this topic and to find out which carriers have been tested for drug release as an adjuvant in the treatment of periodontitis. Considering the inclusion and exclusion criteria, 12 articles were chosen to be part of this review. The selected articles indicated that the drug-releasing carriers in periodontitis treatment were membranes and films fabricated from different types of materials and through various methods. Some of the drugs released by the films and membranes in the selected articles include doxycycline, tetracycline, metronidazole, levofloxacin, and minocycline, all used with good outcome regarding their bactericide effect; BMP-2, Zinc-hydroxyapatite nanoparticles with regenerative effect. The conclusion derived from the selected studies was that gradual drug release in the periodontal pockets is a promising strategy as an adjuvant for the treatment of periodontal disease.

Assessing SARS-CoV-2 Infection Rate among Romanian Dental Practitioners.

Due to the impact of the Covid-19 pandemic on dental treatments, the present research aimed to assess the infection rate among dental practitioners from Romania and to analyze the economic impact of Covid-19 on dental offices. We designed a web-based survey distributed to dental practitioners from Romania. The survey included questions that assessed demographic data from the dentists who completed the questionnaire, along with economic aspects and epidemiological aspects related to the impact of the COVID-19 pandemic on dental practitioners. Five hundred and seven dentists completed the survey. Three-quarters of the assessed dental offices reported a decrease in the income and patient volume compared to 2019. More than half of the patients visiting the dental office paid more attention to the risk of infection and to prevention methods. Most dental offices implemented specific protective equipment for doctors. Three thousand seven hundred thirty-five dental practitioners were working in the 507 assessed dental offices, and among them, 238 COVID-19 cases of contamination were recorded. High contamination rates were registered in October (48, 20.1%), November (66, 27.7%), and December 2020 (52, 21.85%). Contamination mostly took place at home (114 cases, 47.8%) or resulted from event attendance. This study underlines an overall greater level of safety and an increased patient addressability in dental offices.

Impact of COVID-19 on Dental Emergency Services in Cluj-Napoca Metropolitan Area: A Cross-Sectional Study.

This study aimed to assess dental care needs in Cluj region during the State of Emergency, declared due to the COVID-19 pandemic, compared to the same period of the year 2019. A descriptive retrospective analysis was conducted, which retrieved patients seeking emergency dental services at the Emergency Department of County General Hospital and "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania, the only dental service available in April 2020. Recorded data cover the month of April 2020 and is compared with the same period of 2019. During April 2020, 724 patients received dental care, whereas only 160 patients were treated in April 2019 in the same facility. The number of patients with acute apical periodontitis, abscess, and acute pulpitis was significantly higher in 2020. The percentage of patients receiving sedative filling for the treatment of acute pulpitis in 2020 was significantly higher than in 2019, while the proportion of patients receiving pulpectomy was higher in 2019. The percentage of patients receiving endodontic drainage for the treatment of acute periapical periodontitis in 2020 was higher. This study demonstrates that the COVID-19 pandemic impacted the use of medical care services and could further impact the oral health and quality of life of patients.