Effect of Ferulic Acid Loaded in Nanoparticle on Tissue Transglutaminase Expression Levels in Human Glioblastoma Cell Line.

Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.

Regeneration and Long-Term Stability of a Low-Power Eco-Friendly Temperature Sensor Based on a Hydrogel Nanocomposite.

A water-processable and low-cost nanocomposite material, based on gelatin and graphene, has been used to fabricate an environmentally friendly temperature sensor. Demonstrating a temperature-dependent open-circuit voltage between 260 and 310 K, the sensor effectively detects subzero ice formation. Notably, it maintains a constant temperature sensitivity of approximately -19 mV/K over two years, showcasing long-term stability. Experimental evidence demonstrates the efficient regeneration of aged sensors by injecting a few drops of water at a temperature higher than the gelation point of the hydrogel nanocomposite. The real-time monitoring of the electrical characteristics during the hydration reveals the initiation of the regeneration process at the gelation point (~306 K), resulting in a more conductive nanocomposite. These findings, together with a fast response and low power consumption in the range of microwatts, underscore the potential of the eco-friendly sensor for diverse practical applications in temperature monitoring and environmental sensing. Furthermore, the successful regeneration process significantly enhances its sustainability and reusability, making a valuable contribution to environmentally conscious technologies.

Electrochemical Performance of Biopolymer-Based Hydrogel Electrolyte for Supercapacitors with Eco-Friendly Binders.

An environmentally friendly hydrogel based on gelatin has been investigated as a gel polymer electrolyte in a symmetric carbon-based supercapacitor. To guarantee the complete sustainability of the devices, biomaterials from renewable resources (such as chitosan, casein and carboxymethyl cellulose) and activated carbon (from coconut shells) have been used as a binder and filler within the electrode, respectively. The electrochemical properties of the devices have been compared by using cyclic voltammetry, galvanostatic charge/discharge curves and impedance spectroscopy. Compared to the liquid electrolyte, the hydrogel supercapacitors show similar energy performance with an enhancement of stability up to 12,000 cycles (e.g., chitosan as a binder). The most performant device can deliver ca. 5.2 Wh/kg of energy at a high power density of 1256 W/kg. A correlation between the electrochemical performances and charge storage mechanisms (involving faradaic and non-faradaic processes) at the interface electrode/hydrogel has been discussed.

The Face Deepfake Detection Challenge.

Multimedia data manipulation and forgery has never been easier than today, thanks to the power of Artificial Intelligence (AI). AI-generated fake content, commonly called Deepfakes, have been raising new issues and concerns, but also new challenges for the research community. The Deepfake detection task has become widely addressed, but unfortunately, approaches in the literature suffer from generalization issues. In this paper, the Face Deepfake Detection and Reconstruction Challenge is described. Two different tasks were proposed to the participants: (i) creating a Deepfake detector capable of working in an "in the wild" scenario; (ii) creating a method capable of reconstructing original images from Deepfakes. Real images from CelebA and FFHQ and Deepfake images created by StarGAN, StarGAN-v2, StyleGAN, StyleGAN2, AttGAN and GDWCT were collected for the competition. The winning teams were chosen with respect to the highest classification accuracy value (Task I) and "minimum average distance to Manhattan" (Task II). Deep Learning algorithms, particularly those based on the EfficientNet architecture, achieved the best results in Task I. No winners were proclaimed for Task II. A detailed discussion of teams' proposed methods with corresponding ranking is presented in this paper.

Intranasal Administration of a TRAIL Neutralizing Monoclonal Antibody Adsorbed in PLGA Nanoparticles and NLC Nanosystems: An In Vivo Study on a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that progressively compromises cognitive functions. Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL), a proinflammatory cytokine belonging to the TNF superfamily, appears to be a key player in the inflammatory/immune orchestra of the AD brain. Despite the ability of an anti-TRAIL monoclonal antibody to reach the brain producing beneficial effects in AD mice, we attempted to develop such a TRAIL-neutralizing monoclonal antibody adsorbed on lipid and polymeric nanocarriers, for intranasal administration, in a valid approach to overcome issues related to both high dose and drug transport across the blood-brain barrier. The two types of nanomedicines produced showed physico-chemical characteristics appropriate for intranasal administration. As confirmed by enzyme-linked immunosorbent assay (ELISA), both nanomedicines were able to form a complex with the antibody with an encapsulation efficiency of ≈99%. After testing in vitro the immunoneutralizing properties of the nanomedicines, the latter were intranasally administered in AD mice. The antibody-nanocarrier complexes were detectable in the brain in substantial amounts at concentrations significantly higher compared to the free form of the anti-TRAIL antibody. These data support the use of nanomedicine as an optimal method for the delivery of the TRAIL neutralizing antibody to the brain through the nose-to-brain route, aiming to improve the biological attributes of anti-TRAIL-based therapy for AD treatment.

Sorafenib Repurposing for Ophthalmic Delivery by Lipid Nanoparticles: A Preliminary Study.

Uveal melanoma is the second most common melanoma and the most common intraocular malignant tumour of the eye. Among various treatments currently studied, Sorafenib was also proposed as a promising drug, often administered with other compounds in order to avoid resistance mechanisms. Despite its promising cellular activities, the use of Sorafenib by oral administration is limited by its severe side effects and the difficulty to reach the target. The encapsulation into drug delivery systems represents an interesting strategy to overcome these limits. In this study, different lipid nanoparticulate formulations were prepared and compared in order to select the most suitable for the encapsulation of Sorafenib. In particular, two solid lipids (Softisan or Suppocire) at different concentrations were used to produce solid lipid nanoparticles, demonstrating that higher amounts were able to achieve smaller particle sizes, higher homogeneity, and longer physical stability. The selected formulations, which demonstrated to be biocompatible on Statens Seruminstitut Rabbit Cornea cells, were modified to improve their mucoadhesion, evaluating the effect of two monovalent cationic lipids with two lipophilic chains. Sorafenib encapsulation allowed obtaining a sustained and prolonged drug release, thus confirming the potential use of the developed strategy to topically administer Sorafenib in the treatment of uveal melanoma.

Quality by design tools reducing the gap from bench to bedside for nanomedicine.

Pharmaceutical nanotechnology research is focused on smart nano-vehicles, which can deliver active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most varied therapeutical application. The design and development of new nanopharmaceuticals can be very laborious. In recent years, the application of mathematics, statistics and computational tools is emerging as a convenient strategy for this purpose. The application of Quality by Design (QbD) tools has been introduced to guarantee quality for pharmaceutical products and improve translational research from the laboratory bench into applicable therapeutics. In this review, a collection of basic-concept, historical overview and application of QbD in nanomedicine are discussed. A specific focus has been put on Response Surface Methodology and Artificial Neural Network approaches in general terms and their application in the development of nanomedicine to monitor the process parameters obtaining optimized system ensuring its quality profile.

Essential Oil-Loaded NLC for Potential Intranasal Administration.

Complementary and alternative medicines represent an interesting field of research on which worldwide academics are focusing many efforts. In particular, the possibility to exploit pharmaceutical technology strategies, such as the nanoencapsulation, for the delivery of essential oils is emerging as a promising strategy not only in Italy but also all over the world. The aim of this work was the development of nanostructured lipid carriers (NLC) for the delivery of essential oils (Lavandula, Mentha, and Rosmarinus) by intranasal administration, an interesting topic in which Italian contributions have recently increased. Essential oil-loaded NLC, projected as a possible add-on strategy in the treatment of neurodegenerative diseases, were characterized in comparison to control formulations prepared with Tegosoft CT and Neem oil. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size (<200 nm) and good stability were obtained. Morphological and physical-chemical studies showed the formation of different structures depending on the nature of the liquid oil component. In particular, NLC prepared with Lavandula or Rosmarinus showed the formation of a more ordered structure with higher cytocompatibility on two cell lines, murine and human fibroblasts. Taken together, our preliminary results show that optimized positively charged NLC containing Lavandula or Rosmarinus can be proposed as a potential add-on strategy in the treatment of neurodegenerative diseases through intranasal administration, due to the well-known beneficial effects of essential oils and the mucoadhesive properties of NLC.

Ferulic Acid-Loaded Polymeric Nanoparticles for Potential Ocular Delivery.

Ferulic acid (FA) is an antioxidant compound that can prevent ROS-related diseases, but due to its poor solubility, therapeutic efficacy is limited. One strategy to improve the bioavailability is nanomedicine. In the following study, FA delivery through polymeric nanoparticles (NPs) consisting of polylactic acid (NPA) and poly(lactic-co-glycolic acid) (NPB) is proposed. To verify the absence of cytotoxicity of blank carriers, a preliminary in vitro assay was performed on retinal pericytes and endothelial cells. FA-loaded NPs were subjected to purification studies and the physico-hemical properties were analyzed by photon correlation spectroscopy. Encapsulation efficiency and in vitro release studies were assessed through high performance liquid chromatography. To maintain the integrity of the systems, nanoformulations were cryoprotected and freeze-dried. Morphology was evaluated by a scanning electron microscope. Physico-chemical stability of resuspended nanosystems was monitored during 28 days of storage at 5 °C. Thermal analysis and Fourier-transform infrared spectroscopy were performed to characterize drug state in the systems. Results showed homogeneous particle populations, a suitable mean size for ocular delivery, drug loading ranging from 64.86 to 75.16%, and a controlled release profile. The obtained systems could be promising carriers for ocular drug delivery, legitimating further studies on FA-loaded NPs to confirm efficacy and safety in vitro.

A Comparative Evaluation of Sustainable Binders for Environmentally Friendly Carbon-Based Supercapacitors.

Environmentally friendly energy storage devices have been fabricated by using functional materials obtained from completely renewable resources. Gelatin, chitosan, casein, guar gum and carboxymethyl cellulose have been investigated as sustainable and low-cost binders within the electrode active material of water-processable symmetric carbon-based supercapacitors. Such binders are selected from natural-derived materials and industrial by-products to obtain economic and environmental benefits. The electrochemical properties of the devices based on the different binders are compared by using cyclic voltammetry, galvanostatic charge/discharge curves and impedance spectroscopy. The fabricated supercapacitors exhibit series resistance lower than a few ohms and values of the specific capacitance ranged between 30 F/g and 80 F/g. The most performant device can deliver ca. 3.6 Wh/kg of energy at a high power density of 3925 W/kg. Gelatin, casein and carboxymethyl cellulose-based devices have shown device stability up to 1000 cycles. Detailed analysis on the charge storage mechanisms (e.g., involving faradaic and non-faradaic processes) at the electrode/electrolyte interface reveals a pseudocapacitance behavior within the supercapacitors. A clear correlation between the electrochemical performances (e.g., cycle stability, capacitance retention, series resistance value, coulombic efficiency) ageing phenomena and charge storage mechanisms within the porous carbon-based electrode have been discussed.

Hyaluronan/Poly-L-lysine/Berberine Nanogels for Impaired Wound Healing.

Physiological wound healing process can be delayed in the presence of certain pathologies, such as diabetes or cancer. In this perspective, the aim of this study was to design a new nanogel platform of hyaluronan, poly-L-lysine and berberine suitable for wound treatment. Two different nanogel formulations were selected after a first formulation screening. They were prepared by adding dropwise 2 mg/mL hyaluronan aqueous solution (200 or 700 kDa) to 1.25 mg/mL poly-L-lysine aqueous solution. Blank nanogels formulated with 200 kDa HA resulted stable after freeze-drying with dimensions, polydispersity index and zeta potential of 263.6 ± 13.1 nm, 0.323 ± 0.029 and 32.7 ± 3.5 mV, respectively. Both blank and berberine-loaded nanogels showed rounded-shape structures. Loaded nanogels released nearly 50% of loaded berberine within 45 min, whereas the remaining 50% was released up to 24 h in vitro. Both, blank and berberine-loaded nanogels were able to completely close the fibroblasts gap in 42 h.

Recycling of Almond By-Products for Intestinal Inflammation: Improvement of Physical-Chemical, Technological and Biological Characteristics of a Dried Almond Skins Extract.

BACKGROUND: Almond skins are rich in bioactive compounds that undergo oxidation/degradation phenomena and are poorly soluble in water, reducing in vivo absorption and bioavailability, factors that influence the pharmacological activity of an active product. We developed a dried acetonic almond skins extract/cyclodextrin complex to improve extract solubility, dissolution rate and biological activity. METHODS: A lyophilized acetonic almond skin extract was produced. To optimize complex formulation, phase solubility studies and complex characterization (absorption studies, differential scanning calorimetry (DSC), morphology, solubility studies) were performed. To evaluate a possible use in healthy products, tumor necrosis factor-α levels and reactive oxygen species release, as well as cicloxygenase-2 and inducible nitric oxide synthase expression in intestinal epithelial cells, were also evaluated. RESULTS: Phase solubility studies showed a Bs-type profile. A 1:1 dried acetonic almond skins extract/cyclodextrin ratio was able to improve extract water solubility and dissolution rate (100% in 45 min). The UV-Vis spectra of complex revealed a hypsochromic and hyperchromic effect, probably due to a partial inclusion of extract in cyclodextrin cavity through weak bonds, confirmed by DSC and morphology studies. The technological improvement in the extract characteristics also led to better biological activity. In fact, the complex effectively reduces tumor necrosis factor-α levels with respect to the pure extract and significantly inhibits the reactive oxygen species release, even if only at the lower concentration of 5 µg/mL. CONCLUSION: The complex was able to overcome solubility problems and could be used in inflammatory disease.

Optimization of Curcumin Nanocrystals as Promising Strategy for Nose-to-Brain Delivery Application.

Intranasal (IN) drug delivery is recognized to be an innovative strategy to deliver drugs to the Central Nervous System. One of the main limitations of IN dosing is the low volume of drug that can be administered. Accordingly, two requirements are necessary: the drug should be active at a low dosage, and the drug solubility in water must be high enough to accommodate the required dose. Drug nanocrystals may overcome these limitations; thus, curcumin was selected as a model drug to prepare nanocrystals for potential IN administration. With this aim, we designed curcumin nanocrystals (NCs) by using Box Behnken design. A total of 51 formulations were prepared by the sonoprecipitation method. Once we assessed the influence of the independent variables on nanocrystals' mean diameter, the formulation was optimized based on the desirability function. The optimized formulation was characterized from a physico-chemical point of view to evaluate the mean size, zeta potential, polidispersity index, pH, osmolarity, morphology, thermotropic behavior and the degree of crystallinity. Finally, the cellular uptake of curcumin and curcumin NCs was evaluated on Olfactory Ensheathing Cells (OECs). Our results showed that the OECs efficiently took up the NCs compared to the free curcumin, showing that NCs can ameliorate drug permeability.

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies.

Herein, we assessed the effect of Ferulic Acid (FA), a natural antioxidant with anti-cancer effect, on the human glioblastoma cells through molecular and Delayed Luminescence (DL) studies. DL, a phenomenon of ultra-week emission of optical photons, was used to monitor mitochondrial assessment. The effect of FA loaded in nanostructured lipid carriers (NLCs) was also assessed. To validate NLCs as a drug delivery system for glioblastoma treatment, particular attention was focused on their effect. We found that free FA induced a significant decrease in c-Myc and Bcl-2 expression levels accompanied by the apoptotic pathway activation. Blank NLCs, even if they did not induce cytotoxicity and caspase-3 cleavage, decreased Bcl-2, ERK1/2, c-Myc expression levels activating PARP-1 cleavage. The changes in DL intensity and kinetics highlighted a possible effect of nanoparticle matrix on mitochondria, through the involvement of the NADH pool and ROS production that, in turn, activates ERK1/2 pathways. All the effects on protein expression levels and on the activation of apoptotic pathway appeared more evident when the cells were exposed to FA loaded in NLCs. We demonstrated that the observed effects are due to a synergic pro-apoptotic influence exerted by FA, whose bio-availability increases in the glioblastoma cells, and NLCs formulation.

Micelle-nanogel platform for ferulic acid ocular delivery.

Corneal wound healing after a trauma or a chemical injury has been shown to correlate with antioxidant levels at the ocular surface. However, ocular bioavailability of efficient antioxidants (e.g. ferulic acid) after topical administration is limited by their poor solubility, low stability and short residence time. The aim of this work was to formulate ferulic acid in a nanocomposite platform composed of nanogels and micelles for efficient delivery to cornea. Solubility enhancement factor of ferulic acid was found to be equal to 1.9 ± 0.3 and 3.4 ± 0.3 for 50 and 100 mg/ml Pluronic® F68 micellar solutions. Hyaluronan was added to blank and ferulic acid loaded micelles, and then cross-linked with ε-polylysine. Hyaluronan nanogels showed dimensions of ~300 nm with positive zeta potential values. The formulations were characterized in terms of rheological behavior, biocompatibility, wound healing properties, ferulic acid release pattern and penetration into excised bovine corneas. In comparison to Pluronic® micelles that released ferulic acid rapidly, micelle-nanogel composites sustained the release up to 2 days. Furthermore, the micelle-nanogel formulation favored in vitro wound closure promoting fibroblasts growth and ex vivo accumulation of ferulic acid into both healthy and damaged corneas (>100 µg/cm2).

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58±42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/ Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview.

Epilepsy is the fourth most common global neurological problem, which can be considered a spectrum disorder because of its various causes, seizure types, its ability to vary in severity and the impact from person to person, as well as its range of co-existing conditions. The approaches to drug therapy of epilepsy are directed at the control of symptoms by chronic administration of antiepileptic drugs (AEDs). These AEDs are administered orally or intravenously but alternative routes of administration are needed to overcome some important limits. Intranasal (IN) administration represents an attractive route because it is possible to reach the brain bypassing the blood brain barrier while the drug avoids first-pass metabolism. It is possible to obtain an increase in patient compliance for the easy and non-invasive route of administration. This route, however, has some drawbacks such as mucociliary clearance and the small volume that can be administered, in fact, only drugs that are efficacious at low doses can be considered. The drug also needs excellent aqueous solubility or must be able to be formulated using solubilizing agents. The use of nanomedicine formulations able to encapsulate active molecules represents a good strategy to overcome several limitations of this route and of conventional drugs. The aim of this review is to discuss the innovative application of nanomedicine for epilepsy treatment using nose-to-brain delivery with particular attention focused on polymeric nanoparticles to load drugs.

Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of Crocin and Crocetin.

Crocin and crocetin are two interesting constituents of saffron (Crocus sativus) that possess important biological activities. Their use as therapeutic agents is strongly compromised by a scarce stability, poor absorption, and low bioavailability. Therefore, to improve these unfavorable features, the aim of the present work has been to apply a nanotechnological approach based on the formulation of solid lipid nanoparticles containing crocin and crocetin. Solid lipid nanoparticles were formulated according to crocin and crocetin chemical properties, using a variation of the quasi-emulsion solvent diffusion method to formulate crocin-solid lipid nanoparticles, while crocetin-solid lipid nanoparticles were prepared following the solvent diffusion method. Morphology and dimensional distribution of solid lipid nanoparticles have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively, while the effect of drug incorporation versus time has been studied by Turbiscan technology. In order to verify the role of the nanotechnological approach on the biological activities of crocin and crocetin, the antioxidant and antiproliferative effects of these carotenoids once incorporated in lipid nanoparticles have been evaluated. For this aim, the oxygen radical absorbance capacity assay and the MTT test were used, respectively.The results pointed out the formulation of nanometric dispersions endowed with high homogeneity and stability, with an encapsulation efficiency ranging from 80 (crocetin-solid lipid nanoparticles) to 94% (crocin-crocetin). The oxygen radical absorbance capacity assay evidenced an interesting and prolonged antioxidant activity of crocin and crocetin once encapsulated in solid lipid nanoparticles, while the nanoencapsulation strategy showed a different mechanism in ameliorating the cytotoxic effect of these two substances.

Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents.

The brain as a target for drug delivery is a challenge in pharmaceutical research. Among the several proposed strategies, the intranasal route represents a good strategy to deliver drugs to the brain. The goal of this study was to investigate the potential use of oxcarbazepine (OXC) to enhance brain targeting efficiency after intranasal (IN) administration. As well as attempting to use as low a dose as possible to obtain therapeutic effect. Our results showed that, after IN administrations, the dose of OXC that was effective in controlling epileptic seizures was 0.5 mg/kg (1 dose, every 20 min for 1 h) in rodents, confirmed by Cerebral Spinal Fluid (CSF) bioavailability. With the aim of reducing the number of administrations, sustaining drug release and increasing brain targeting, OXC was loaded into poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs). The selected nanoformulation for in vivo studies was obtained re-suspending the freeze-dried and cryo-protected OXC loaded PLGA NPs. The translocation of 1-1'-Dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine Iodide loaded PLGA NPs, from nose to the brain, was confirmed by Fluorescence Molecular Tomography, which also evidenced an accumulation of NPs in the brain after repeated IN administrations. IN administrations of OXC loaded PLGA NPs reduced the number of administrations to 1 over 24 h compared to the free drug thus controlling seizures in rats. Immunohistochemical evaluations (anti-neurofilament, anti-beta tubulin, and anti-caspase3) demonstrated a neuroprotective effect of OXC PLGA NPs after 16 days of treatment. These encouraging results confirmed the possibility of developing a novel non-invasive nose to brain delivery system of OXC for the treatment of epilepsy.

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58 ± 42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.