Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using “OCSCC” as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment.

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.

The present study evaluated the effects of low-level laser therapy (LLLT) by means of a diode laser in accelerating orthodontic tooth movement (OTM). After extraction of the first upper premolars for orthodontic purpose, 82 maxillary canines which needed distalization were analyzed in 41 enrolled patients (21 males, 20 females, mean age 13.4 ± 2.1 years). On all experimental sites, an orthodontic force of 50/N was applied by a nickel-titanium (NiTi) closed coil spring (G&H, Franklin, IN, USA) in order to obtain the space closure. Using a split mouth randomized design, the test side was treated using a diode laser (Wiser Laser Doctor Smile, Brendola, Italy) operating at 810 nm wavelength in continuous wave mode at both the buccal and palatal side on three points/side (distal, medial and mesial) (1 W output power, continuous wave of 66.7 J/cm², energy density of 8 J) at baseline and at 3, 7, and 14 days and every 15 days until the space closed. On the control side, the opposite selected canine was treated only using orthodontic traction. The primary outcome chosen was the overall time needed to complete the levelling and closing space, measured on a study cast. The secondary outcome chosen was the evaluation of pain levels related to tooth traction, using a Visual Analogue Scale (VAS), recorded at 3, 7, and 14 days after treatments. The mean space closures of the maxillary canines were comparable between groups [Test, 4.56 mm (95% CI 3.9–4.8); Control, 4.49 mm (95% CI 3.8–4.7), p = 0.456]. The laser group yielded less mean time [84.35 ± 12.34 days (95% CI 79.3–86)] to accomplish space closure compared to the control group [97.49 ± 11.44 days (91.7–102.3)] (p < 0.001). The test side showed a significant reduction in the average range of dental pain at 3 [Test, 5.41 (95% CI 5.1–5.6); Control, 7.23 (95% CI 6.9–7.6), p < 0.001], 7 [Test, 4.12 (95% CI 3.8–4.7); Control, 5.79 (95% CI 5.4–5.8), p < 0.001], and at 14 days [Test, 2.31 (95% CI 1.8–2.3); Control, 3.84 (95% CI 3.3–4.2), p < 0.001] after treatment (p < 0.001). This study demonstrates that the use of LLLT therapy was effective in accelerating tooth movement and reducing pain levels related to OTM.

Introduction: Drug combination is widely used to treat chronic inflammatory diseases. A similar strategy might be worth of interest to design plant-derived natural products to treat inflammatory conditions. Curcumin is a natural phenolic compound which shares anti-inflammatory activity with both flavocoxid, a flavonoid mixture of baicalin and catechin, and β-caryophyllene, a bicyclic sesquiterpene. The aim of this study was to investigate the synergy potential of curcumin with both flavocoxid and β-caryophyllene in human articular chondrocytes triggered with lipopolysaccharide (LPS), in an experimental in vitro model of osteoarthritis.Materials and Methods: Human articular chondrocytes were stimulated with LPS alone or in combination with different treatments. Total RNA was extracted 4 h after treatment to study interleukin 1β (IL-1β), NF-κB, and STAT3 mRNA expression. A drug combination study was designed choosing 5 doses to demonstrate a synergistic effect of compounds, according to Chou and Talalay method. A median-effect equation was applied and finally, the combination index (CI) was used to clarify the nature of the compounds interaction (synergistic versus additive versus antagonistic inhibitory effects); CI < 1, CI = 1, and CI > 1 indicated synergistic, additive, and antagonistic effects, respectively.Results: LPS prompted IL-1β expression. Curcumin, flavocoxid and β-caryophyllene suppressed IL-1β expression with different IC₅₀. A synergistic action for the reduction of the inflammatory phenotype in human chondrocytes was observed for the combination curcumin-flavocoxid with a percentage from 10% to 90%, and for the combination curcumin-β-caryophyllene from 50% to 90%. IC₅₀ doses of either flavocoxid, β-caryophyllene and curcumin alone or in combination were safe and did not affect cell vitality. Moreover, the same IC₅₀ doses reduced the transcription factors NF-κB and STAT3 mRNA expression and interestingly the effects of the combinations were greater than the natural products alone, thus suggesting that the site where the synergy takes place could be at the signal transduction level.Discussion: The results suggest that curcumin synergizes with either flavocoxid or β-caryophyllene, exerting an anti-inflammatory activity and thus strongly suggesting the potential of a dual combination of these compounds for the management of osteoarthritis and unmasking a new feature of these natural products.

Obesity is a worldwide growing problem for the health care systems and its treatment is strongly recommended. Orlistat, naltrexone/bupropion, and liraglutide are approved for weight loss in Italy in patients with a Body Mass Index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 with concomitant diseases. However, the prescription of these drugs is significantly low worldwide. General practitioners (GPs) play a key role in the early diagnosis and appropriate management of obesity. The aim of the study was to investigate the management of obesity and the prescriptive attitude of anti-obesity drugs in a general practice setting. All patients registered in lists of 8 GPs with a recorded diagnosis of obesity or BMI values ≥ 30 kg/m2 in the period 2017-2018, were recruited. A descriptive analysis of demographic and clinical characteristic was carried out. The Spearman's correlation rank test was applied to identify correlations between BMI and all the variables of interest. Among 1301 obese patients, only 66.1 % had been diagnosed and 29.4 % had no registered BMI value. Patients with recorded BMI, were overweight (7.8 %) or in the obesity class I (38.8 %), class II (14.1 %), and class III (7.1 %), respectively. The obese patients (class 1-3) were older [66 (55-76) vs 49 (32-59); p < 0.01], and had more concurrent diseases [5 (3-8) vs 4 (2-6); p < 0.01] than patients who reached a BMI < 30 Kg/m2. Moreover, most of obese were high cardiovascular risk (HCVr) patients (67.0 % vs 31.9 %; p < 0.01). The BMI was directly related to age (rs 0.14; p < 0.01), diabetes (rs 0.19; p < 0.01), hypertension (rs 0.14; p < 0.01), heart failure (rs 0.09; p < 0.01), HCVr (rs 0. 12; p < 0.01) and number of comorbidities (rs 0.08; p = 0.01). No prescriptions of orlistat or naltrexone/bupropion were found. Liraglutide was prescribed only in 7 patients because of the concomitant presence of diabetes. Our results suggest a low adherence to guide line recommendations for obesity management and confirm an under-prescription of anti-obesity drugs in Italy.

The extracellular matrix of the articular disc in a temporomandibular joint (TMJ) is composed mainly of collagen I and elastin. The collagen is important for resisting tensile forces, while the elastin is responsible to maintain the shape after deformation. We studied the orientation of collagen and elastin in a normal human temporomandibular joint disc by light microscopy, immunofluorescence and scanning electron microscopy. Our results demonstrated that collagen and elastin run parallel to each other in the intermediate zone with an anteroposterior orientation. From here, the orientation of two fibers groups changes into a disordered arrangement in the transition zone. Numerous elastic fibers cross with the collagen fibers, defining an interwoven knitted arrangement. The evaluation of the disc–condyle relationship shows that the medial margin of the articular disc is inserted directly at the superficial layer of the mandibular condylar cartilage. Therefore, the tensile properties of the TMJ disc are expressed in the directions corresponding to the orientation of the collagen fibers, and the complex orientation of elastin with the collagen determines the maintaining of the shape after the stresses by the joint movements. Moreover, the direct anatomical relationship between the articular disc and the mandibular condyle makes a decisive contribution to the understanding of TMJ movements.