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    Optimization of resveratrol used as a scaffold to design histone deacetylase (HDAC-1 and HDAC-2) inhibitors
    (MDPI, 2022-10-13) Urias, Beatriz Silva [UNESP]; Pavan, Aline Renata [UNESP]; Albuquerque, Gabriela Ribeiro [UNESP]; Prokopczyk, Igor Muccilo [UNESP]; Alves, Tânia Mara Ferreira [UNESP]; de Melo, Thais Regina Ferreira [UNESP]; Sartori, Geraldo Rodrigues; da Silva, João Hermínio Martins; Man Chin, Chung [UNESP]; Dos Santos, Jean Leandro [UNESP]; Universidade Estadual Paulista (Unesp)
    Histone deacetylases (HDAC) are epigenetic enzymes responsible for repressing gene expression through the deacetylation of histone lysine residues. Therefore, inhibition of HDACs has become an interesting approach for the treatment of several diseases, including cancer, hematology, neurodegenerative, immune diseases, bacterial infections, and more. Resveratrol (RVT) has pleiotropic effects, including pan-inhibition of HDAC isoforms; however, its ability to interfere with membranes requires additional optimization to eliminate nonspecific and off-target effects. Thus, to explore RVT as a scaffold, we designed a series of novel HDAC-1 and -2 inhibitors containing the 2-aminobenzamide subunit. Using molecular modeling, all compounds, except unsaturated compounds (4) and (7), exhibited a similar mode of interaction at the active sites of HDAC 1 and 2. The docking score values obtained from the study ranged from −12.780 to −10.967 Kcal/mol. All compounds were synthesized, with overall yields ranging from 33% to 67.3%. In an initial screening, compounds (4), (5), (7), and (20)–(26), showed enzymatic inhibitory effects ranging from 1 to 96% and 6 to 93% against HDAC-1 and HDAC-2, respectively. Compound (5), the most promising HDAC inhibitor in this series, was selected for IC50 assays, resulting in IC50 values of 0.44 µM and 0.37 µM against HDAC-1 and HDAC-2, respectively. In a panel of selectivity against HDACs 3–11, compound (5) presented selectivity towards Class I, mainly HDAC-1, 2, and 3. All compounds exhibited suitable physicochemical and ADMET properties as determined using in silico simulations. In conclusion, the optimization of the RVT structure allows the design of selective HDAC inhibitors, mainly targeting HDAC-1 and HDAC-2 isoforms.
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    Vascular effects of the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate
    (MDPI, 2022-10-24) Terroni, Barbara [UNESP]; de Moraes, Luis Henrique Oliveira [UNESP]; Pavan, Aline Renata [UNESP]; Rodrigues, Gerson Jhonatan; Dos Santos, Jean Leandro [UNESP]; Universidade Estadual Paulista (Unesp)
    Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of vascular properties leads to endothelial dysfunction (ED) and cardiovascular damage. Some diseases, such as sickle cell anemia, are characterized by ED with reduction in the levels of nitric oxide (NO). Previously, we have shown that the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (Lapdesf-4c) could act as NO donor, inhibiting platelet aggregation and reducing the inflammation associated with SCA. However, the vascular effect of this compound was not yet studied. Herein, we evaluated the effects of Lapdesf-4c in vascular reactivity experiments using aortic rings from male Wistar rats (300 g/90 days). We have found that Lapdesf-4c induced vasodilation in the presence (E+) or absence of endothelium (E−) with an average of EMax values of 101.8 ± 3.33% and 111.8 ± 3.21%. The mechanism of action was studied using 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), L-NG-nitroarginine methyl ester (L-NAME), and hydroxocobalamin. The EMax values for those pathways were hydroxocobalamin (30.6 ± 2.21%), ODQ (4.75 ± 0.51%), and L-NAME (109 ± 3.65), suggesting that Lapdesf-4c exhibits NO-dependent mechanisms. Lapdesf-4c was able to prevent angiotensin-induced ED after incubation of aorta rings for 1 h. We found based on the concentration–effect curve using acetylcholine (ACh) that pEC50 values for the control, Ang II, and combination of (Ang II + Lapdesf-4c) were 6.73, 6.46, and 7.15, respectively. In conclusion, Lapdesf-4c has emerged as a new drug candidate that can promote vasodilation and act as a protective agent against ED, being useful to prevent vascular damage.
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    Editorial: Epigenetic therapy against cancer: toward new molecular targets and technologies
    (2023-01-01) Sousa, Ângela; Soares, Christiane P. [UNESP]; Chin, Chung Man [UNESP]; Trisciuoglio, Daniela; Valdes-Mora, Fatima; University of Beira Interior; Universidade Estadual Paulista (UNESP); UNION of the Colleges of the GREAT LAKES (UNILAGO); Sapienza University of Rome; Children’s Cancer Institute Australia Randwick; Garvan Institute of Medical Research Darlinghurst
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    Functionalization of Nanosystems in Cancer Treatment
    (2022-01-01) Luiz, Marcela Tavares; Dutra, Jessyca Aparecida Paes [UNESP]; De Araújo, Jennifer Thayanne Cavalcante [UNESP]; Di Filippo, Leonardo Delello [UNESP]; Duarte, Jonatas Lobato [UNESP]; Chorilli, Marlus [UNESP]; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
    Cancer is the major public health problem worldwide, with high rates of incidence and lethality. The leak of specificity of the treatments currently available results in several side effects and reduced efficacy. Thus, nanosystems have demonstrated great potential for the delivery of chemotherapeutic agents to tumors due to their ability to passively accumulate in the tumor through enhanced permeability and retention (EPR) effect, to carry of hydrophilic and hydrophobic drugs, and to protect the drugs against degradation. In recent decades, advances in nanosystems design have expanded their therapeutic potential due to the inclusion of targeting ligands that can be specifically recognized by receptors overexpressed on tumor cells. Among these targeting ligands, antibodies, antibodies’ fragments, peptides, and small molecules have been widely incorporated in nanosystems for promoting the active targeting to the tumors. The modification of nanosystems with these ligands can be performed before or after nanosystems’ production through non-covalent or covalent functionalization, which can result in different biological activities. In this context, the present chapter aims to present some aspects of the synthesis employed to functionalize nanosystems. In addition, we address the main targeting ligands used for promoting the active targeting of nanosystems to different cancer cells, discussing the in vitro and in vivo results obtained for each functionalization.
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    Three-dimensional culture models: emerging platforms for screening the antitumoral efficacy of nanomedicines
    (2023-03-01) Tofani, Larissa Bueno; Luiz, Marcela Tavares [UNESP]; Paes Dutra, Jessyca Aparecida [UNESP]; Abriata, Juliana Palma; Chorilli, Marlus [UNESP]; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
    Nanomedicines have been investigated for delivering drugs to tumors due to their ability to accumulate in the tumor tissues. 2D in vitro cell culture has been used to investigate the antitumoral potential of nanomedicines. However, a 2D model cannot adequately mimic the in vivo tissue conditions because of the lack of cell-cell interaction, a gradient of nutrients and the expression of genes. To overcome this limitation, 3D cell culture models have emerged as promising platforms that better replicate the complexity of native tumors. For this purpose, different techniques can be used to produce 3D models, including scaffold-free, scaffold-based and microfluidic-based models. This review addresses the principles, advantages and limitations of these culture methods for evaluating the antitumoral efficacy of nanomedicines.
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    (2022-01-01) de Sousa, Ângela Maria Almeida; Soares, Christiane Pienna [UNESP]; Chorilli, Marlus [UNESP]; University of Beira Interior; Universidade Estadual Paulista (UNESP)
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    Cancer Nanotechnology
    (2022-01-01) de Sousa, Ângela Maria Almeida; Soares, Christiane Pienna [UNESP]; Chorilli, Marlus [UNESP]; University of Beira Interior; Universidade Estadual Paulista (UNESP)
    Cancer nanotechnology is a growing, emerging area of cross-disciplinary research that aims to develop efficient, specific and noninvasive approaches to restore the health and well-being of all cancer patients through more effective diagnosis and treatment. This new volume serves as a fundamental guide to cutting-edge topics in cancer nanotechnology, including advances in therapy, the use of nanoparticles and nanomaterials, future directions for nanocarriers in cancer therapy, and the application of DNA and RNA nanovaccines. Organized into four sections, the volume presents an overview of research and innovation in the emerging field of nanotechnology as a powerful tool in the diagnosis, imaging and treatment of cancer. International experts author chapters addressing targets of cancer therapy, materials for cancer nanotechnology, strategies for cancer therapy using nanotechnology, and innovative nanotechnologies for cancer diagnosis and treatment. The volume will be useful for a broad audience, including cross-disciplinary researchers, trainees, health professionals, and experts in industry.
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    Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease
    (2023-07-01) Fonseca-Santos, Bruno [UNESP]; Cazarin, Camila André; da Silva, Patrícia Bento; dos Santos, Kaio Pini [UNESP]; da Rocha, Márcia Cristina Oliveira; Báo, Sônia Nair; De-Souza, Márcia Maria; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal da Bahia (UFBA); Postgraduate in Pharmaceutical Sciences; University of Brasilia (UnB)
    Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.
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    A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas
    (2023-06-01) Di Filippo, Leonardo Delello [UNESP]; de Carvalho, Suzana Gonçalves [UNESP]; Duarte, Jonatas Lobato [UNESP]; Luiz, Marcela Tavares [UNESP]; Paes Dutra, Jessyca Aparecida [UNESP]; de Paula, Geanne Aparecida [UNESP]; Chorilli, Marlus [UNESP]; Conde, João; Universidade Estadual Paulista (UNESP); Universidade NOVA de Lisboa
    Gliomas are the most common type of brain cancer, and among them, glioblastoma multiforme (GBM) is the most prevalent (about 60% of cases) and the most aggressive type of primary brain tumor. The treatment of GBM is a major challenge due to the pathophysiological characteristics of the disease, such as the presence of the blood-brain barrier (BBB), which prevents and regulates the passage of substances from the bloodstream to the brain parenchyma, making many of the chemotherapeutics currently available not able to reach the brain in therapeutic concentrations, accumulating in non-target organs, and causing considerable adverse effects for the patient. In this scenario, nanocarriers emerge as tools capable of improving the brain bioavailability of chemotherapeutics, in addition to improving their biodistribution and enhancing their uptake in GBM cells. This is possible due to its nanometric size and surface modification strategies, which can actively target nanocarriers to elements overexpressed by GBM cells (such as transmembrane receptors) related to aggressive development, drug resistance, and poor prognosis. In this review, an overview of the most frequently overexpressed receptors in GBM cells and possible approaches to chemotherapeutic delivery and active targeting using nanocarriers will be presented.
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    Hybrid Membranes of the Ureasil-Polyether Containing Glucose for Future Application in Bone Regeneration
    (2023-05-01) da Silva, Camila Garcia [UNESP]; Monteiro, João Rodrigues [UNESP]; Oshiro-Júnior, João Augusto; Chiavacci, Leila Aparecida [UNESP]; Universidade Estadual Paulista (UNESP); State University of Paraiba (UEPB)
    The application of mesenchymal stem cells (MSC) in bone tissue regeneration can have unpredictable results due to the low survival of cells in the process since the lack of oxygen and nutrients promotes metabolic stress. Therefore, in this work, polymeric membranes formed by organic–inorganic hybrid materials called ureasil-polyether for modified glucose release were developed in order to overcome the problems posed by a of lack of this nutrient. Thus, membranes formed by polymeric blend of polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with 6% glucose incorporation were developed. Physical–chemical characterization techniques were performed, as well as tests that evaluated thermal properties, bioactivity, swelling, and release in SBF solution. The results of the swelling test showed an increase in membrane mass correlated with an increase in the concentration of ureasil-PEO500 in the polymeric blends. The membranes showed adequate resistance when subjected to the application of a high compression force (15 N). X-ray diffraction (XRD) evidenced peaks corresponding to orthorhombic crystalline organization, but the absence of glucose-related peaks showed characteristics of the amorphous regions of hybrid materials, likely due to solubilization. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to glucose and hybrid materials were similar to that seen in the literature, however when glucose was incorporated into the PEO500, an increase in rigidity occurs. In PPO400, and in the blends of both materials, there was a slight decrease in Tg values. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material compared to other membranes. The membranes showed bioactivity and hemocompatibility in vitro. The in vitro release test revealed that it is possible to control the release rate of glucose and the kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasil-polyether membranes have great potential to be used as a glucose release system, and their future application has the potential to optimize the bone regeneration process.
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    Pharmacological, toxicological and phytochemical analysis of Spondias dulcis parkinson
    (2023-01-01) Fernandes, Felipe Hugo Alencar [UNESP]; Soares, Sabrina da Silva; Bekbolatova, Elmira; Boylan, Fábio; Salgado, Hérida Regina Nunes [UNESP]; Universidade Estadual Paulista (UNESP); UNIFACISA Centro Universitário; Heidelberg University; JSC National Medical University; Trinity College Dublin
    Spondias dulcis Parkinson have been used in traditional medicine in Asia, Oceania, and South America, for different diseases conditions and as a functional food. The scientific literature described as different potential pharmacology such as antioxidant, anti-inflammatory, antimicrobial, thrombolytic and enzymatic inhibitor. This study aimed to: (1) establish the pharmacological activity in intestinal motility in vivo and antioxidant activity in vitro; (2) perform the acute toxicology test in mouse; (3) characterize the phytochemical profile based on counter-current chromatography (CCC) and NMR analysis. The results revealed a laxative effect of S. dulcis extract and a high antioxidant activity (IC50 = 5.10 for DPPH assay and 14.14 for hydrogen peroxide scavenging test). No side effects were observed in the oral acute toxicity test for a dose up to 2000 mg/kg. The chemical profile was identified by CCC and NMR, and the comparison of the data obtained with previous literature revealed the presence of the flavonoid rutin (Quercetin-3-O-rutinoside) in the extract.
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    Evaluation of photodynamic therapy on nanoparticles and films loaded-nanoparticles based on chitosan/alginate for curcumin delivery in oral biofilms
    (2023-06-15) Silvestre, Amanda Letícia Polli [UNESP]; dos Santos, Aline Martins [UNESP]; de Oliveira, Analú Barros [UNESP]; Ferrisse, Túlio Morandin [UNESP]; Brighenti, Fernanda Lourenção [UNESP]; Meneguin, Andréia Bagliotti [UNESP]; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP)
    Nanoparticles and nanoparticle-loaded films based on chitosan/sodium alginate with curcumin (CUR) are promising strategies to improve the efficacy of antimicrobial photodynamic therapy (aPDT) for the treatment of oral biofilms. This work aimed to develop and evaluate the nanoparticles based on chitosan and sodium alginate encapsulated with CUR dispersed in polymeric films associated with aPDT in oral biofilms. The NPs were obtained by polyelectrolytic complexation, and the films were prepared by solvent evaporation. The photodynamic effect was evaluated by counting Colony Forming Units (CFU/mL). Both systems showed adequate characterization parameters for CUR release. Nanoparticles controlled the release of CUR for a longer period than the nanoparticle-loaded films in simulated saliva media. Control and CUR-loaded nanoparticles showed a significant reduction of 3 log10 CFU/mL against S. mutans biofilms, compared to treatment without light. However, biofilms of S. mutans showed no photoinactivation effect using films loaded with nanoparticles even in the presence of light. These results demonstrate the potential of chitosan/sodium alginate nanoparticles associated with aPDT as carriers for the oral delivery of CUR, offering new possibilities to improve the treatment of dental caries and infections. This work will contribute to advances in the search for innovative delivery systems in dentistry.
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    Development, characterization and in vitro cytotoxicity of kaempferol-loaded nanostructured lipid carriers in glioblastoma multiforme cells
    (2023-06-01) Nicoleti, Luisa Ribeiro [UNESP]; Di Filippo, Leonardo Delello [UNESP]; Duarte, Jonatas Lobato [UNESP]; Luiz, Marcela Tavares [UNESP]; Sábio, Rafael Miguel [UNESP]; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP)
    Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of − 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells.
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    New Technological Approaches for Dental Caries Treatment: From Liquid Crystalline Systems to Nanocarriers
    (2023-03-01) Luiz, Marcela Tavares [UNESP]; di Filippo, Leonardo Delello [UNESP]; Dutra, Jessyca Aparecida Paes [UNESP]; Viegas, Juliana Santos Rosa; Silvestre, Amanda Letícia Polli [UNESP]; Anselmi, Caroline [UNESP]; Duarte, Jonatas Lobato [UNESP]; Calixto, Giovana Maria Fioramonti [UNESP]; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP); Universidade do Porto
    Dental caries is the most common oral disease, with high prevalence rates in adolescents and low-income and lower-middle-income countries. This disease originates from acid production by bacteria, leading to demineralization of the dental enamel and the formation of cavities. The treatment of caries remains a global challenge and the development of effective drug delivery systems is a potential strategy. In this context, different drug delivery systems have been investigated to remove oral biofilms and remineralize dental enamel. For a successful application of these systems, it is necessary that they remain adhered to the surfaces of the teeth to allow enough time for the removal of biofilms and enamel remineralization, thus, the use of mucoadhesive systems is highly encouraged. Among the systems used for this purpose, liquid crystalline systems, polymer-based nanoparticles, lipid-based nanoparticles, and inorganic nanoparticles have demonstrated great potential for preventing and treating dental caries through their own antimicrobial and remineralization properties or through delivering drugs. Therefore, the present review addresses the main drug delivery systems investigated in the treatment and prevention of dental caries.
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    Hybrid Magnetic Lipid-Based Nanoparticles for Cancer Therapy
    (2023-03-01) Luiz, Marcela Tavares [UNESP]; Dutra, Jessyca Aparecida Paes [UNESP]; Viegas, Juliana Santos Rosa; de Araújo, Jennifer Thayanne Cavalcante [UNESP]; Tavares Junior, Alberto Gomes [UNESP]; Chorilli, Marlus [UNESP]; Universidade Estadual Paulista (UNESP); Universidade do Porto
    Cancer is one of the major public health problems worldwide. Despite the advances in cancer therapy, it remains a challenge due to the low specificity of treatment and the development of multidrug resistance mechanisms. To overcome these drawbacks, several drug delivery nanosystems have been investigated, among them, magnetic nanoparticles (MNP), especially superparamagnetic iron oxide nanoparticles (SPION), which have been applied for treating cancer. MNPs have the ability to be guided to the tumor microenvironment through an external applied magnetic field. Furthermore, in the presence of an alternating magnetic field (AMF) this nanocarrier can transform electromagnetic energy in heat (above 42 °C) through Néel and Brown relaxation, which makes it applicable for hyperthermia treatment. However, the low chemical and physical stability of MNPs makes their coating necessary. Thus, lipid-based nanoparticles, especially liposomes, have been used to encapsulate MNPs to improve their stability and enable their use as a cancer treatment. This review addresses the main features that make MNPs applicable for treating cancer and the most recent research in the nanomedicine field using hybrid magnetic lipid-based nanoparticles for this purpose.
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    Cost of Illness in Patients With COVID-19 Admitted in three Brazilian Public Hospitals
    (2023-07-01) Oliveira, Layssa Andrade; Lucchetta, Rosa Camila [UNESP]; Mendes, Antônio Matoso; Bonetti, Aline de Fátima; Xavier, Cecilia Silva [UNESP]; Sanches, Andréia Cristina Conegero; Borba, Helena Hiemisch Lobo; Oliota, Ana Flávia Redolfi; Rossignoli, Paula; Mastroianni, Patrícia de Carvalho [UNESP]; Venson, Rafael; Virtuoso, Suzane; de Nadai, Tales Rubens [UNESP]; Wiens, Astrid; Federal University of Paraná; Universidade Estadual Paulista (UNESP); Hospital Alemão Oswaldo Cruz; Clinics Hospital Complex of the Federal University of Paraná; State University of Western Paraná; Paraná State Health Department; University of Glasgow
    Objectives: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. Methods: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. Results: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. Conclusions: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.
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    Lyotropic liquid crystal mesophases as transdermal delivery systems for lipophilic drugs: A comparative study
    (2023-04-05) de Araujo, Guilherme Rodolfo Souza; Azevedo Lima, Odeanny Vitória; Barreto Neujahr, João Pedro; Matos, Saulo Santos; de Souza, Thalisson Amorim; dos Santos, Aline Martins [UNESP]; Chorilli, Marlus [UNESP]; de Souza Araujo, Adriano Antunes; Duarte, Marcelo Cavalcante; da Cunha Gonsalves, Joyce Kelly Marinheiro; de Souza Nunes, Rogéria; dos Santos, Marcio Roberto Viana; Vitorino Sarmento, Victor Hugo; Moreira Lira, Ana Amélia; Universidade Federal de Sergipe (UFS); Federal University of Paraíba; Universidade Estadual Paulista (UNESP); Federal University of Vale do São Francisco
    The present work aimed to evaluate different Liquid Crystal Mesophases (LCM) as transdermal drug delivery systems (TDDS) for nifedipine (NFD), a lipophilic drug model. The formulations composed of water, Citrus sinensis essential oil (CSEO), PPG-5-CETETH-20, and Olive oil ester PEG-7 were obtained and characterized by polarized light microscopy (PLM), rheology, small-angle x-ray scattering (SAXS), Fourier transform infrared coupled with an attenuated total reflection accessory (FTIR-ATR) and in vitro assays: bioadhesion, drug release, skin permeation, and retention tests. As a result, changes in component proportions led to several transparent viscous systems with an anisotropic profile. PLM and SAXS proved the presence of lamellar (S1), hexagonal (S3), and lamellar + hexagonal (S2) LCM, and rheology showed a high viscoelasticity profile. LCMs were able to adhere to the skin, and S2 achieved higher adhesion strength. NFD (5 mg/mL) has not modified the organization of LCMs. Results also showed that S3 promoted higher permeation and retention and higher disorganization of stratum corneum lipids, which is the main permeation-enhancing mechanism. Thus, the formulations obtained can carry and improve drug delivery through the skin and are promising TDDS for lipophilic drug administration, such as NFD.
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    Design and Characterization of Lipid-Surfactant-Based Systems for Enhancing Topical Anti-Inflammatory Activity of Ursolic Acid
    (2023-02-01) Fonseca-Santos, Bruno [UNESP]; Araujo, Giovanna Angeli [UNESP]; Ferreira, Paula Scanavez [UNESP]; Victorelli, Francesca Damiani [UNESP]; Pironi, Andressa Maria [UNESP]; Araújo, Victor Hugo Sousa [UNESP]; Carvalho, Suzana Gonçalves [UNESP]; Chorilli, Marlus [UNESP]; Universidade Federal da Bahia (UFBA); Universidade Estadual Paulista (UNESP)
    Skin inflammation is a symptom of many skin diseases, such as eczema, psoriasis, and dermatitis, which cause rashes, redness, heat, or blistering. The use of natural products with anti-inflammatory properties has gained importance in treating these symptoms. Ursolic acid (UA), a promising natural compound that is used to treat skin diseases, exhibits low aqueous solubility, resulting in poor absorption and low bioavailability. Designing topical formulations focuses on providing adequate delivery via application to the skin surface. The aim of this study was to formulate and characterize lipid-surfactant-based systems for the delivery of UA. Microemulsions and liquid crystalline systems (LCs) were characterized by polarized light microscopy (PLM), rheology techniques, and textural and bioadhesive assays. PLM supported the self-assembly of these systems and elucidated their formation. Rheologic examination revealed pseudoplastic and thixotropic behavior appropriate, and assays confirmed the ability of these formulations to adhere to the skin. In vivo studies were performed, and inflammation induced by croton oil was assessed for response to microemulsions and LCs. UA anti-inflammatory activities of ~60% and 50% were demonstrated by two microemulsions and 40% and 35% by two LCs, respectively. These data support the continued development of colloidal systems to deliver UA to ameliorate skin inflammation.
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    COVID-19 Stress on Mental and Hair Health: A Marker for Diseases in the Post-Pandemic Era
    (2022-01-01) Accorsi, Daniela Xavier; Dos Santos, Ingrid Aparecida Mendes [UNESP]; Accorsi, Juliana Xavier; Abelan, Ursulandréa Sanches [UNESP]; Martin Júnior, Celso [UNESP]; Bohac, Silvia; Bumiller-Bini, Valéria; Boldt, Angelica Beate Winter; Chin, Chung Man [UNESP]; Union of the Colleges of the Great Lakes (UNILAGO); Universidade Estadual Paulista (UNESP); School of Medicine (FACERES); Quantum Psychology Clinic; Universidade Federal do Paraná (UFPR)
    The seriousness of the COVID-19 pandemic with accumulating stress factors, including lack of pharmacotherapy, quarantine, social distancing, delay of vaccination, and economic uncertainties, may foster fear and psychiatric disorders that can precipitate or aggravate hair/scalp disease. Hair loss can lead to decreased self-esteem, potentiating the negative effects on social life and generating a vicious cycle of stress during the pandemic. The relationship between environment and behavior can also trigger epigenetic changes in diseases, which may influence the health of the next generations. In this review, we describe the interaction between the physiological mechanisms of stress on hair follicles and hair disorders and openly discuss during pandemic/post-pandemic (not genetically determined but epigenetically triggered) hair loss as a point of concern as a health marker for further development of chronic diseases, such as diabetes, obesity, psychiatric disorders, and others.
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    Pleiotropic Effects of Nitric Oxide on SARS-CoV-2 Infections
    (2021-01-01) Terroni, Barbara [UNESP]; Lopes, Juliana Romano [UNESP]; Chin, Chung Man [UNESP]; Dos Santos, Jean Leandro [UNESP]; Universidade Estadual Paulista (UNESP); Union of the College of the Great Lakes (UNILAGO)
    Infection by β-coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coron-avirus-2) alters the homeostasis of the vascular endothelium, promoting an inflammatory state which causes damage and favors the prothrombotic state. The direct viral cytotoxicity induced by the SARS-CoV-2 leads to endothelial cell death; thus, altering the vessel functions. Moreover, SARS-CoV infection induces endothelial dysfunction (ED) and reduces the levels of nitric oxide (NO); thus, aggravating the vascular injuries, which promotes thrombotic events due to an altera-tion in the homeostasis. NO is a pleiotropic molecule that induces vasodilation, regulates the immune response, inhibits platelet aggregation, and decreases the cellular adhesion to vascular en-dothelium. Moreover, NO acts directly against invasive agents, exhibiting antibacterial, antiviral, and antifungal activity. High levels of NO result in an increase in the ED, causing an inflammatory amplification that aggravates the disease through undesirable positive feedback. The objective of this review was to present and discuss the involvement of NO on ED in SARS-CoV-2 infections. This review may also highlight new perspectives for therapeutic interventions through the supple-mentation of exogenous NO. The maintenance of homeostatic NO levels could represent a useful approach in the prevention of coronavirus-induced ED.