Silencing of heat shock factor 1 (HSF1) inhibits proliferation, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma. METHODS: Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line. RESULTS: Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001). CONCLUSION: Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

Using infrared thermography to detect subclinical mastitis in dairy cows in compost barn systems.

This study aimed to evaluate the use of thermal imaging obtained by infrared thermography (IRT) to detect cases of subclinical mastitis in dairy cows under commercial conditions of compost barn systems in a region of Brazil with a semiarid climate. Twenty-eight crossbred cows were evaluated twice a day for one week using IRT. Three thermal images were obtained for each cow, referring to the anatomical regions of the right and left fore udder and rear udder. A computer program was used to analyze the images and obtain the right fore udder temperature (RFUT, °C), left fore udder temperature (LFUT, °C), rear udder temperature (RUT, °C), and average udder temperature (AUT, °C). In addition, samples of milk from each quarter of the udder were collected for somatic cell count (SCC) to correlate the diseases observed on the thermal image with any infection in the udder region. The results obtained using IRT were subjected to regression and correlation analyses. It was observed that LFUT, RAQT, RUT, and AUT were adjusted in quadratic polynomial models with good prediction of SCC (i.e., infection) with R2 = 0.92, 0.97, 0.86, and 0.94, respectively. The region of the anterior quarters of the udder was the most promising for imaging, stronger correlations were obtained between LFUT and RFUT with SCC (r = 0.87 and 0.88, respectively). The IRT is a practical technology capable of detecting cases of mastitis in dairy cows with good precision, especially with thermal images from the anatomical region of the front quarters of the udder. However, more detailed studies are needed to make thermal imaging processing a more useful method for routine activities on farms in compost barn systems.

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis.

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

Sedentary behavior is associated with musculoskeletal pain in adolescents: A cross sectional study.

BACKGROUND: High prevalence of back pain has been observed in adolescents. Sedentary behavior (SB) is considered a risk factor for musculoskeletal pain. The association between back pain and SB in the pediatric/adolescent population is not well established. OBJECTIVE: To investigate the association between SB and low back and neck pain in adolescents according to sex. METHODS: This is a cross-sectional study with children and adolescents aged 10-17 years, randomly recruited from public and private schools in Presidente Prudente, Brazil. All students enrolled in the selected schools were eligible to participate. SB was evaluated by adding the number of hours of use of screen devices, such as television, computer, video game, and smartphone/tablet. To assess neck and low back pain, the Nordic Musculoskeletal Questionnaire was used. Physical activity and socioeconomic status were assessed by the Baecke Questionnaire and the Brazilian Criteria for Economic Classification (ABEP), respectively. Odds ratio (OR) from Binary Logistic Regression in the unadjusted and adjusted model (physical activity, abdominal obesity, and socioeconomic status) showed the relationship between musculoskeletal pain and SB. RESULTS: A total of 1011 adolescents (557 girls) with a mean ± standard deviation age of 13.2±2.4 years were included. Moderate (OR = 1.80; 95%CI: 1.00, 3.23) and high (OR = 1.91; 95%CI: 1.02, 3.53) SB were associated with neck pain in girls. In boys, moderate SB (OR = 2.75; 95%CI: 1.31, 5.78) were associated with neck pain. Moderate (OR = 2.73; 95%CI: 1.45, 5.02) and high (OR = 2.49; 95%CI: 1.30, 4.76) SB were associated with low back pain only in girls. CONCLUSION: Moderate and high SB were associated with neck pain in girls and boys, while moderate and high SB were associated with low back pain only in girls.

Combat Time in International Male Judo Competitions: A Systematic Review and Meta-Analysis.

This study aimed to synthesize literature data on male judo combat time in international competitions between 2010 and 2019. The search was carried out from May 8th to June 11th, 2021, in electronic databases using the following keywords: ("technical-tactical" OR "time motion" OR "combat time") AND ("judo" OR "combat sports" OR "martial arts"). After the selection process, 8 articles were included in the systematic review and 7 in the meta-analysis. These studies analyzed 2,562 international male judo combats over the years 2010-2019. We observed that the average male judo combat time changed (2010 = 202.8; 2011-2012 = 304.8; 2016 = 237.4; 2018-2019 = 189.8 s) after each rule change (2010, 2013, 2017, and 2018). There was a significant difference between combats that ended up to the regular time and those that needed overtime (Golden Score: 2013 = 3% vs. 2018-2019 = 21%; p = 0.03). There were differences between 60 kg (p ≤ 0.019) and + 100 kg (p ≤ 0.04) categories and the others in 2011-2012. However, no significant difference was found between the combat time by weight division after the 2017 rule changes, although there are still differences in relation to the end of the combats (p < 0.001). There were significant changes in the male judo combat time with each rule change (2010, 2013, 2017, and 2018), and the data from the included studies point to a trend of homogeneity in the combat time spent between the weight divisions over the years, and an increase in the occurrence of Golden Score. More studies need to be carried out to identify the new temporal behaviors of athletes.

Cutaneous leishmaniasis: new oral therapeutic approaches under development.

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

Enhanced Solubility of Albendazole in Cyclodextrin Inclusion Complex: A Molecular Modeling Approach and Physicochemical Evaluation.

BACKGROUND: Albendazole (ABZ) is the drug of choice for the treatment of a variety of human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins (CD) are pharmaceutical excipients with the ability to modulate the solubilization property of hydrophobic molecules. OBJECTIVE: The aim of the study was to analyze through in vitro and in silico studies (Autodock Vina software and CycloMolder platform) the formation of inclusion complexes between ABZ, ß-cyclodextrin (ß-CD) and its derivatives Methyl-ß-cyclodextrin (M-ß-CD) and Hydroxypropyl-ß-cyclodextrin (HP-ß-CD). METHODS: The most stable inclusion complexes were produced by the kneading method and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), determination of the ABZ content and in vitro dissolution profile. RESULTS: Molecular modeling revealed that inclusion complexes between HP-ß-CD:ABZ (in the proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular interactions, showing that the use of more cyclodextrins does not generate gains in the stability of the complex. On the characterization tests, the complexes experimentally obtained by the kneading method demonstrated highly suggestive parameters, including ABZ in HP-ß-CD in both molar proportions, suppression of bands in the infrared spectrum, displacement of the drug's melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals in the XRD and a release of more than 80% of ABZ in less than 5 minutes, dissolution efficiency of up to 92%. CONCLUSION: In silico studies provided a rational selection of the appropriate complexes of cyclodextrin, enabling the elaboration of more targeted complexes, decreasing time and costs for elaboration of new formulations, thereby increasing the oral biodisponibility of ABZ.

Technical-Tactical Behaviors Analysis of Male and Female Judo Cadets' Combats.

This brief research report showed technical-tactical behaviors of male and female judo cadets during combats, comparing the frequency and time of judo combat actions, techniques and penalties. The data was composed for 3,240 sequential technical-tactical behavior analysis from 108 female and 300 male cadet combats recorded of public judo championships. Combat, standing combat moments, approach action, gripping action, attack, groundwork actions and pause moment were observed and determinant technical-tactical behaviors (frequencies of actions, penalties and type of attacks) analysis were done with FRAMI software, followed by Mann-Whitney and Student's t-test, p ≤ 0.05. Our main results indicated that male cadets with 58.66s ± 50.26s demonstrated longer gripping action than female with 38.44s ± 30.44s, as standing combat (tachi-waza) had differences between male with 96.8s ± 72s and female athletes with 75.85s ± 56.97s. Moreover, male cadets had higher sacrifice techniques (sutemi-waza) actions than female athletes. This information could be used to a best performance associated with "psyching-up" as much as it could be used on physical training and technical-tactical ability of female and male cadets.

Innovation Overview of Nanoparticle-Based Dermatological Products: A Patent Study.

BACKGROUND: The health area in its most diverse fields has progressively incorporated nanotechnology into its products, such as in dermatology. In this sector, nanoparticles are one of the strategies that allow improvements, both in terms of value-added, as well as the efficacy, safety and stability of products for cosmetic or therapeutic purposes. OBJECTIVE: To understand the scenario of development and innovation of dermatological products with nanoparticles, through a patent prospection, evaluating the annual evolution, the main technology investors countries, the profile of the depositors, besides the uses and purposes of the products. METHODS: The Espacenet® database was used for consultation, using the search term "nanoparticle and skin". A total of 285 patents were found, of which 208 were available and 89 were based on the scope. RESULTS: There was a progressive evolution in the number of patents after the year 2000, with South Korea, the United States, China and Japan as the main depositor countries. Private companies and Education and Research Institutions were the entities with the largest amount of deposits. The cosmetic purpose was the predominant use compared to the therapeutic one. The most prominent nanoparticles were polymeric, metallic and lipid, while the therapeutic area presented a larger number of the functionalized ones. CONCLUSION: The market for dermatological products has been innovating and growing over the years through the use of nanoparticles, evidencing a prominent development of nanotechnology-based cosmetics. Countries investing in nanotechnology and major developers of innovative products are highlighted in this scenario.

Green Analytical Methods for the Separation of Seven Antihistamines: Application in Separation of Azelastine and Related Impurities in Nasal Solution.

Antihistamines are widely used to alleviate the symptoms caused by allergic reactions. Most of these drugs have zwitteriónicas and/or amphoteric characteristics, which confer additional analytical challenges. This work aimed to develop a single eco-friendly and efficient chromatographic methods for analysis of seven antihistamines, namely, azelastine HCl, desloratadine, ebastine, fexofenadine HCl, ketotifen, loratadine, and olopatadine HCl. The separations were obtained using RP C-18 LUNA (150x4.6mm, 5 µm) column. The mobile phase consisted of acetonitrile and acidified water (pH 2.1) in the following proportion: 15:85, v/v for desloratadine, 25:75, v/v for ketotifen and olopatadine, 32:68, v/v for fexofenadine, 35:65, v/v for azelastine and loratadine, and 45:55, v/v for ebastine. All separations were obtained in less than 7.0 min. A prototype method was fully validated and applied in the assay of azelastine HCl in nasal solutions. The proposed methods for analysis of seven antihistamines are highly efficient, selective, and sensitive. Moreover, all methods can be considered excellent in terms of greenness, with total organic residue < 2.5 mL/analysis. An improved gradient method is also described for separation of azelastine HCl and its related impurities.

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population.

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2-330 T>G (rs2069762); IL4-590 C>T (rs2243250); IL6-174 G>C (rs1800795); IL10-592 A>C (rs1800872); IL10-1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.

A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases.

The goal of this study was to identify a host gene signature that can distinguish tuberculosis (TB) from other pulmonary diseases (OPD). We conducted real-time PCR on whole blood samples from patients in Brazil. TB and OPD patients (asthma and non-TB pneumonia) differentially expressed granzyme A (GZMA), guanylate binding protein 5 (GBP5) and Fc gamma receptor 1A (CD64). Receiver operating characteristic, tree classification and random forest analyses were applied to evaluate the discriminatory power of the three genes and find the gene panel most predictive of patients' disease classification. Tree classification produced a model based on GBP5 and CD64 expression. In random forest analysis, the combination of the three genes provided a robust biosignature to distinguish TB from OPD with 95% specificity and 93% sensitivity. Our results suggest that GBP5 and CD64 in tandem may be the most predictive combination. However, GZMA contribution to the prediction model requires further investigation. Regardless, these three genes show promise as a rapid diagnostic marker separating TB from OPD.

Bioactive compounds and antioxidant activity of Ximenia americana coming from different collection sites

The study aimed to evaluate the bioactive compounds and antioxidant activity of edible fraction (pulp and peel) in green and ripe ripening stages of the fruit and the seed of wild plum (Ximenia americana L.) from different production sites of occurrence in the semiarid region of Brazil. To characterize the edible fraction, the experiment was conducted in a completely randomized design in a factorial 3 x 2, where the first factor was the collection sites and the second factor the maturation stages, with 4 repetitions with 25 fruits each. As for seeds the experiment was conducted in a completely randomized design with 4 repetitions, totaling 25 seeds per experimental plot. The fruits were collected in the communities of Mulunguzinho, Pau Branco and Mata do Meio in the county of Mossoró, RN, Brazil. The edible fraction of the fruit Ximenia americana contains high levels of vitamin C (160,26 mg/100 g), yellow flavonoids (43,12 mg/100 g), total extractable polyphenols (3066,48 mg/100 g) and antioxidant activity (365,55 g fruit/g DPPH e 251,70 μmol Trolox/g) and the seeds contain content of polyphenols (2067,56 mg/100 g) and antioxidant (373,80 g fruit/g DPPH e 279,96 251,70 μmol Trolox/g). The edible part of the green fruit contains higher content of total extractable polyphenols, total carotenoids, yellow flavonoids and total anthocyanins. The edible portion of the fruits and the seeds from the community of Pau Branco contains the lowest content of total extractable polyphenols and antioxidant activity(AU)

Compostos bioativos e atividade antioxidante de Ximenia americana oriunda de diferentes locais de coleta. O trabalho teve como objetivo avaliar os compostos bioativos e a atividade antioxidante da fração comestível (polpa e casca) nos estádios de maturação verde e maduro do fruto e da semente da ameixa silvestre (Ximenia americana L.) proveniente de diferentes locais de ocorrência de produção na região semiárida do Brasil. Para caracterização da fração comestível o experimento foi conduzido em delineamento inteiramente casualizado em esquema fatorial 3 x 2, sendo o primeiro fator os locais de coleta e o segundo fator os estádios de maturação, com 4 repetições com 25 frutos cada. Já para as sementes o experimento foi conduzido em delineamento inteiramente casualizado, com 4 repetições, totalizando 25 sementes por parcela experimental. Os frutos foram coletados nas comunidades de Mulunguzinho, Pau Branco e Mata do Meio, no município de Mossoró, RN, Brasil. A fração comestível do fruto da Ximenia americana contém elevados teores de vitamina C (160,26 mg/100 g), flavonoides amarelos (43,12 mg/100 g), polifenóis extraíveis totais (3066,48 mg/100 g) e atividade antioxidante (365,55 g fruit/g DPPH e 251,70 μmol Trolox/g) e as sementes elevados teores de polifenóis (2067,56 mg/100 g) e atividade antioxidante (373,80 g fruit/g DPPH e 279,96 251,70 μmol Trolox/g). A fração comestível do fruto verde contém maior conteúdo de polifenóis extraíveis totais, carotenoides totais, flavonoides amarelos e antocianina totais. A fração comestível e as sementes dos frutos provenientes da comunidade de Pau Branco contém menor conteúdo de polifenóis extraíveis totais e atividade antioxidante(AU)