Targeted therapy using nanocomposite delivery systems in cancer treatment: highlighting miR34a regulation for clinical applications.

The clinical application of microRNAs in modern therapeutics holds great promise to uncover molecular limitations and conquer the unbeatable castle of cancer metastasis. miRNAs play a decisive role that regulating gene expression at the post-transcription level while controlling both the stability and translation capacity of mRNAs. Specifically, miR34a is a master regulator of the tumor suppressor gene, cancer progression, stemness, and drug resistance at the cell level in p53-dependent and independent signaling. With changing, trends in nanotechnology, in particular with the revolution in the field of nanomedicine, nano drug delivery systems have emerged as a prominent strategy in clinical practices coupled with miR34a delivery. Recently, it has been observed that forced miR34a expression in human cancer cell lines and model organisms limits cell proliferation and metastasis by targeting several signaling cascades, with various studies endorsing that miR34a deregulation in cancer cells modulates apoptosis and thus requires targeted nano-delivery systems for cancer treatment. In this sense, the present review aims to provide an overview of the clinical applications of miR34a regulation in targeted therapy of cancer.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. METHODS: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. RESULTS: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. CONCLUSIONS: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. METHODS: 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). CONCLUSIONS: Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP.

Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk.

While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a "three-way relationship" linking diabetes, periodontitis, and physical activity.

Antibiotics to prevent complications following tooth extractions.

BACKGROUND: The most frequent indications for tooth extractions, generally performed by general dental practitioners, are dental caries and periodontal infections. Systemic antibiotics may be prescribed to patients undergoing extractions to prevent complications due to infection. This is an update of a review first published in 2012. OBJECTIVES: To determine the effect of systemic antibiotic prophylaxis on the prevention of infectious complications following tooth extractions. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health Trials Register (to 16 April 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 3), MEDLINE Ovid (1946 to 16 April 2020), Embase Ovid (1980 to 16 April 2020), and LILACS (1982 to 16 April 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials of systemic antibiotic prophylaxis in patients undergoing tooth extraction(s) for any indication. DATA COLLECTION AND ANALYSIS: At least two review authors independently performed data extraction and 'Risk of bias' assessment for the included studies. We contacted trial authors for further details where these were unclear. For dichotomous outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. For continuous outcomes, we used mean differences (MD) with 95% CI using random-effects models. We examined potential sources of heterogeneity. We assessed the certainty of the body of evidence for key outcomes as high, moderate, low, or very low, using the GRADE approach. MAIN RESULTS: We included 23 trials that randomised approximately 3206 participants (2583 analysed) to prophylactic antibiotics or placebo. Although general dentists perform dental extractions because of severe dental caries or periodontal infection, only one of the trials evaluated the role of antibiotic prophylaxis in groups of patients affected by those clinical conditions. We assessed 16 trials as being at high risk of bias, three at low risk, and four as unclear.  Compared to placebo, antibiotics may reduce the risk of postsurgical infectious complications in patients undergoing third molar extractions by approximately 66% (RR 0.34, 95% CI 0.19 to 0.64; 1728 participants; 12 studies; low-certainty evidence), which means that 19 people (95% CI 15 to 34) need to be treated with antibiotics to prevent one infection following extraction of impacted wisdom teeth. Antibiotics may also reduce the risk of dry socket by 34% (RR 0.66, 95% CI 0.45 to 0.97; 1882 participants; 13 studies; low-certainty evidence), which means that 46 people (95% CI 29 to 62) need to take antibiotics to prevent one case of dry socket following extraction of impacted wisdom teeth. The evidence for our other outcomes is uncertain: pain, whether measured dichotomously as presence or absence (RR 0.59, 95% CI 0.31 to 1.12; 675 participants; 3 studies) or continuously using a visual analogue scale (0-to-10-centimetre scale, where 0 is no pain) (MD -0.26, 95% CI -0.59 to 0.07; 422 participants; 4 studies); fever (RR 0.66, 95% CI 0.24 to 1.79; 475 participants; 4 studies); and adverse effects, which were mild and transient (RR 1.46, 95% CI 0.81 to 2.64; 1277 participants; 8 studies) (very low-certainty evidence).  We found no clear evidence that the timing of antibiotic administration (preoperative, postoperative, or both) was important. The included studies enrolled a subset of patients undergoing dental extractions, that is healthy people who had surgical extraction of third molars. Consequently, the results of this review may not be generalisable to all people undergoing tooth extractions. AUTHORS' CONCLUSIONS: The vast majority (21 out of 23) of the trials included in this review included only healthy patients undergoing extraction of impacted third molars, often performed by oral surgeons. None of the studies evaluated tooth extraction in immunocompromised patients. We found low-certainty evidence that prophylactic antibiotics may reduce the risk of infection and dry socket following third molar extraction when compared to placebo, and very low-certainty evidence of no increase in the risk of adverse effects. On average, treating 19 healthy patients with prophylactic antibiotics may stop one person from getting an infection. It is unclear whether the evidence in this review is generalisable to patients with concomitant illnesses or patients at a higher risk of infection. Due to the increasing prevalence of bacteria that are resistant to antibiotic treatment, clinicians should evaluate if and when to prescribe prophylactic antibiotic therapy before a dental extraction for each patient on the basis of the patient's clinical conditions (healthy or affected by systemic pathology) and level of risk from infective complications. Immunocompromised patients, in particular, need an individualised approach in consultation with their treating medical specialist.

Development of lung metastases in mouse models of tongue squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) represents 3%-4% of all cancers. Despite the increasing incidence of OSCC distant metastasis and poor prognosis, few animal models of OSCC distant metastasis have been reported. In this study, we established mouse models of OSCC lung metastasis by orthotopic and tail vein injection of new OSCC cell lines. METHODS: For the tail vein model, we used a novel cell line isolated from lung metastases reproduced in vivo after intravenous injection of HSC-3 GFP/luciferase cells and sorted for GFP expression (HSC-3 M1 GFP/luciferase). Lung metastases were assessed by imaging techniques and further confirmed by histology. For the orthotopic model, HSC-3 GFP/luciferase cells were injected into the tongue of athymic nude mice. The primary tumor and metastases were assessed by in vivo imaging, histology, and immunohistochemistry. RESULTS: The orthotopic model presented spontaneous lung metastases in 50% of the animals and lymph node metastases were present in 83% of cases. In the tail vein model, a lung metastasis rate of 60% was observed. CONCLUSIONS: Lung metastases were successfully reproduced by orthotopic and tail vein injection. Since lymph node metastases were present, the orthotopic model with HSC-3 GFP/luciferase cells may be suitable to investigate metastatic dissemination in OSCC.

Posture Assessment in Dentistry for Different Visual Aids Using 2D Markers.

Attention and awareness towards musculoskeletal disorders (MSDs) in the dental profession has increased considerably in the last few years. From recent literature reviews, it appears that the prevalence of MSDs in dentists concerns between 64 and 93%. In our clinical trial, we have assessed the dentist posture during the extraction of 90 third lower molars depending on whether the operator performs the intervention by the use of the operating microscope, surgical loupes, or with the naked eye. In particular, we analyzed the evolution of the body posture during different interventions evaluating the impact of visual aids with respect to naked eye interventions. The presented posture assessment approach is based on 3D acquisitions of the upper body, based on planar markers, which allows us to discriminate spatial displacements up to 2 mm in translation and 1 degree in rotation. We found a significant reduction of neck bending in interventions using visual aids, in particular for those performed with the microscope. We further investigated the impact of different postures on MSD risk using a widely adopted evaluation tool for ergonomic investigations of workplaces, named (RULA) Rapid Upper Limb Assessment. The analysis performed in this clinical trial is based on a 3D marker tracker that is able to follow a surgeon's upper limbs during interventions. The method highlighted pros and cons of different approaches.

Patient attitude and habits regarding removable denture home hygiene and correlation with prosthesis cleanliness: A cross-sectional study of elderly Italians.

STATEMENT OF PROBLEM: With the aging population, an increasing number of patients will require removable dental prostheses. Despite the recent public efforts to improve oral healthcare, knowledge of hygiene procedures for removable dental prostheses is sparse. PURPOSE: The purpose of this cross-sectional study was to determine, through questionnaires, the level of awareness and education of home hygiene procedures among elderly Italian individuals wearing removable dental prostheses and to correlate self-reported hygiene habits and prosthesis cleanliness, as determined by a clinical examination. MATERIAL AND METHODS: A cross-sectional study was performed by questionnaires administered by a dental hygienist to patients attending the dental clinics (prosthodontic and periodontology clinical units) at San Paolo Hospital of Milan from January 2014 to October 2015 and who volunteered to participate. The questionnaire included demographic data and oral hygiene habits. Each participant received an intraoral and prosthesis examination performed by the same dental hygienist. The cleanliness of the removable dental prosthesis was classified according to a 3-point scoring system. Categorical variables were expressed as a percentage of study participants and compared by using the χ2 test, while, for the statistical correlations between continuous and categorical variables, the point-biserial correlation calculator was used (α=.05). RESULTS: Questionnaires were collected from 161 study participants: 92 women (mean ±standard deviation age: 76 ±7.59 years; range: 65-93 years) and 69 men (mean ±standard deviation age: 74 ±6.31 years; range: 65-86 years). A total of 239 prostheses were considered. A significant correlation was found between older participants, older removable dental prostheses, and reduced prosthesis cleanliness, correlating age ranges of participants as well as of removable dental prostheses with the degrees of prosthesis cleanliness (P=.001 and P=.004, respectively). Half the study participants (n=81; 50.3%) reported prosthesis removal during the night, while the others reported sleeping with the prosthesis in place. Some study participants (n=32; 19.9%) reported that they had never received instructions about how to clean the prosthesis. Mechanical brushing with toothbrush and toothpaste was the most common cleaning method (n=47; 29.2%), while the recommended combined cleaning method based on both mechanical brushing and immersion in dental cleanser was applied by 34 (21.1%) study participants. A similar number (n=25; 15.5%) reported at least 1 episode of denture-related stomatitis. CONCLUSIONS: In the analyzed cohort, patient attitude and habits toward home procedures for denture hygiene resulted in poor prosthesis cleanliness. Most individuals used a toothbrush and toothpaste to clean their device, although combining mechanical and chemical cleaning is typically reported to be the optimal method.

Evidence-Based Phytoiatry, a New Approach in Crop Protection.

In the past decades, the scientific quality of biomedical studies has been hierarchically depicted in the well-known pyramid of evidence-based medicine (EBM), with higher and higher levels of evidence moving from the base to the top. Such an approach is missing in the modern crop protection and, therefore, we introduce, for the first time, this novel concept of evidence-based phytoiatry in this field. This editorial is not a guideline on plant protection products (PPP) registration, but rather a scientific and technical support for researchers involved in the general area of plant pathology, providing them with evidence-based information useful to design critically new studies.

Anti-inflammatory and wound healing effects of an essential oils-based bioadhesive gel after oral mucosa biopsies: preliminary results.

Post-operative management of patients receiving oral biopsy includes the control of edema, pain, infection, and re-epithelization at the surgical site. This clinical study investigates the topical use of a bioadhesive gel, containing essential oils, to promote wound healing and prevent post-operative pain and infection, avoiding the need for surgical suture and chlorhexidine applications. Ten patients, who needed to receive oral biopsies (≤6 mm in diameter) for the diagnosis of mucosal oral lesions, were enrolled. The bioadhesive gel successfully controlled the post-surgical pain; at 1-week follow-up visit, no signs of infection nor side effects were reported and the surgical sites were completely healed. The bioadhesive gel resulted in a very promising agent for the post-operative management of oral biopsy site, without the need for surgical suture and chlorhexidine applications.

Phytotherapeutics in cancer invasion and metastasis.

Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities.

Carvacrol and human health: A comprehensive review.

Carvacrol (CV) is a phenolic monoterpenoid found in essential oils of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperwort (Lepidium flavum), wild bergamot (Citrus aurantium bergamia), and other plants. Carvacrol possesses a wide range of bioactivities putatively useful for clinical applications such antimicrobial, antioxidant, and anticancer activities. Carvacrol antimicrobial activity is higher than that of other volatile compounds present in essential oils due to the presence of the free hydroxyl group, hydrophobicity, and the phenol moiety. The present review illustrates the state-of-the-art studies on the antimicrobial, antioxidant, and anticancer properties of CV. It is particularly effective against food-borne pathogens, including Escherichia coli, Salmonella, and Bacillus cereus. Carvacrol has high antioxidant activity and has been successfully used, mainly associated with thymol, as dietary phytoadditive to improve animal antioxidant status. The anticancer properties of CV have been reported in preclinical models of breast, liver, and lung carcinomas, acting on proapoptotic processes. Besides the interesting properties of CV and the toxicological profile becoming definite, to date, human trials on CV are still lacking, and this largely impedes any conclusions of clinical relevance.

Ethnobotany of the genus Taraxacum-Phytochemicals and antimicrobial activity.

Plants belonging to the genus Taraxacum have been used in traditional healthcare to treat infectious diseases including food-borne infections. This review aims to summarize the available information on Taraxacum spp., focusing on plant cultivation, ethnomedicinal uses, bioactive phytochemicals, and antimicrobial properties. Phytochemicals present in Taraxacum spp. include sesquiterpene lactones, such as taraxacin, mongolicumin B, and taraxinic acid derivatives; triterpenoids, such as taraxasterol, taraxerol, and officinatrione; and phenolic derivatives, such as hydroxycinnamic acids (chlorogenic, chicoric, and caffeoyltartaric acids), coumarins (aesculin and cichoriin), lignans (mongolicumin A), and taraxacosides. Aqueous and organic extracts of different plant parts exhibit promising in vitro antimicrobial activity relevant for controlling fungi and Gram-positive and Gram-negative bacteria. Therefore, this genus represents a potential source of bioactive phytochemicals with broad-spectrum antimicrobial activity. However, so far, preclinical evidence for these activities has not been fully substantiated by clinical studies. Indeed, clinical evidence for the activity of Taraxacum bioactive compounds is still scant, at least for infectious diseases, and there is limited information on oral bioavailability, pharmacological activities, and safety of Taraxacum products in humans, though their traditional uses would suggest that these plants are safe.

Aloe Genus Plants: From Farm to Food Applications and Phytopharmacotherapy.

Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among the most economically important medicinal plants and are commonly used in primary health treatment, where they play a pivotal role in the treatment of various types of diseases via the modulation of biochemical and molecular pathways, besides being a rich source of valuable phytochemicals. In the present review, we summarized the recent advances in botany, phytochemical composition, ethnobotanical uses, food preservation, and the preclinical and clinical efficacy of Aloe plants. These data will be helpful to provide future directions for the industrial and medicinal use of Aloe plants.

Plants of the Melaleuca Genus as Antimicrobial Agents: From Farm to Pharmacy.

Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80-90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd.