Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection

Ligand polyvalency is a powerful modulator of protein–receptor interactions. Host–pathogen infection interactions are often mediated by glycan ligand–protein interactions, yet its interrogation with very high copy number ligands has been limited to heterogenous systems. Here we report that through the use of nested layers of multivalency we are able to assemble the most highly valent glycodendrimeric constructs yet seen (bearing up to 1,620 glycans). These constructs are pure and well-defined single entities that at diameters of up to 32 nm are capable of mimicking pathogens both in size and in their highly glycosylated surfaces. Through this mimicry these glyco-dendri-protein-nano-particles are capable of blocking (at picomolar concentrations) a model of the infection of T-lymphocytes and human dendritic cells by Ebola virus. The high associated polyvalency effects (β>106, β/N ~102–103) displayed on an unprecedented surface area by precise clusters suggest a general strategy for modulation of such interactions.España MICINN CTQ2008-01694España MICINN CTQ2011-2341

Adaptation of Ancient Techniques to Recreate ‘Wines’ and ‘Beverages’ Using Withered Grapes of Muscat of Alexandria

The production of wines using ancient techniques is a present trend with commercial interest among consumers valorising their historical background. Therefore, the objective of the present work was to recreate wines and piquettes produced from dehydrated grapes, vinified according to the techniques described in classical Roman agricultural manuals. Muscat of Alexandria grapes were harvested and subjected to greenhouse drying under ambient temperature for 7 days, during the 2020 and 2021 harvests. When weight loss was approximately 30%, grapes were processed according to different protocols, including a rehydration step using saltwater or white wine (2020 harvest). Fermentation was conducted with the addition of commercial yeast without sulphur dioxide supplementation. The piquettes were obtained from the pressed pomaces diluted with water solution (5 g/L tartaric acid). The 2020 wines showed alcoholic content and residual sugar ranging from 14.8 to 17.0% (v/v), and 0.8 g/L to 18 g/L, respectively. Volatile acidity was less than 1 g/L (as acetic acid) in all wines, except for the fermentation of crushed grapes alone, which yielded 2.3 g/L volatile acidity. The fermentation of dehydrated crushed grapes in the semi-industrial trial run in the harvest of 2021 yielded 1.1 g/L volatile acidity. The piquettes analysis showed ethanol ranging from 10.2% (v/v) to 16.0% (v/v), reducing substances less than 2 g/L and volatile acidity less than 0.8 g/L. Overall, the physicochemical analysis showed that it was possible to recreate ancient winemaking techniques that may be further improved to produce commercially and legally acceptable winesinfo:eu-repo/semantics/publishedVersio

Maternal periodontitis induces intergenerational injuries on reproductive performance of adult female rat offspring

Substantial evidence suggests a direct link between periodontitis in pregnant women and subsequent adverse pregnancy outcomes. However, no studies have evaluated the transgenerational effects of periodontitis on the reproductive performance of subsequent generations. The present study investigated whether maternal periodontal disease exerts deleterious transgenerational effects on reproductive performance in F1 female rats. Rat female offspring from mothers that were subjected to experimentally induced periodontitis or sham operation were mated with sexually experienced male rats. The weight and reproductive performance of these F1 offspring were evaluated on gestation day 21, including maternal weight, litter weight, individual pup weight, number of pups, and number of resorptions. The percentage of dams with resorptions and the litter weight/number of pups were also calculated. Compared with the control group, an increase was observed in the percentage and number of resorptions and litter weight/number of pups, and a decrease was observed in the number of pups born in the experimental group. Maternal weight, litter weight, and individual pup weight were not different between the control and experimental groups. Maternal periodontitis impaired reproductive performance in the F1 generation. We showed that periodontitis may induce reproductive injury in adult offspring even if the offspring do not undergo any inflammatory/infectious process during their postnatal life or during gestation. These findings reinforce the importance of oral care during pregnancy. Existem evidências substanciais de uma relação direta entre periodontite em mulheres grávidas com efeitos adversos reprodutivos. No entanto, nenhum estudo avaliou os efeitos intergeracionais da periodontite sobre o desempenho reprodutivo das gerações subsequentes. O presente estudo investigou se a doença periodontal materna exerce efeitos intergeracionais deletérios sobre o desempenho reprodutivo em ratos fêmeas da geração F1. Assim, filhas de ratas cujas mães foram submetidas a periodontite experimental ou falsamente operadas foram acasaladas com ratos machos sexualmente experientes. O peso corporal e desempenho reprodutivo da geração F1 foram avaliados no dia 21 de gestação, incluindo o peso materno, peso da ninhada, peso da individual dos filhotes, número de filhotes e de reabsorções. A percentagem de fêmeas com reabsorção e o peso da ninhada/número de filhotes também foram calculados. Comparados com o grupo controle, observou-se aumento na porcentagem e número de reabsorções e no peso da ninhada/ número de filhotes, e decréscimo no número de filhotes nascidos no grupo experimental. O peso materno, peso da ninhada e individual dos filhotes não foi diferente entre o controle e experimental. Estes resultados mostram que a periodontite experimental materna prejudica o desempenho reprodutivo da geração F1, mesmo que estes animais não tenham sido expostos diretamente a um processo inflamatório

Protective effect of topical Cordia verbenacea in a rat periodontitis model: immune-inflammatory, antibacterial and morphometric assays

BACKGROUND: This study evaluated the effects of C. verbenacea essential oil topically administered in a rat periodontitis model. METHODS: Periodontitis was induced on rats in one of the mandibular first molars assigned to receive a ligature. Animals were randomly divided into two groups: a) non-treatment group (NT) (n = 18): animals received 1mL of vehicle; b) C. verbenacea group (C.v.) (n = 18): animals received 5mg/Kg of essential oils isolated from C. verbenacea. The therapies were administered topically 3 times daily for 11 days. Then, the specimens were processed for morphometric analysis of bone loss. The ligatures were used for microbiological assessment of the presence of Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Porphyromonas gingivalis using PCR. The gingival tissue was collected to Elisa assay of interleukin (IL)-1α and IL-10 levels. RESULTS: Bone loss was inhibited by C. verbenacea when compared to the NT group (p < 0.05). A decrease in the levels of IL-1α and increase in the IL-10 amounts was observed in the C.v. group as compared to NT group (p < 0.05). A lower frequency of P. gingivalis was found in C.v. group (p < 0.05). CONCLUSION: C. verbenacea essential oil topically administered diminished alveolar bone resorption, promoting a positive local imbalance in the pro/anti-inflammatory system and reducing the frequency of detection of P. gingivalis

Estudo comparativo in vitro da rugosidade radicular após instrumentação com ultrassom e pontas sônicas diamantadas

OBJECTIVE: The purpose of this study was to evaluate the root surface roughness after instrumentation with hand curette and diamond-coated sonic and universal ultrasonic tips. MATERIALS AND METHODS: Forty root surfaces of human teeth were randomly assigned to four treatment groups: control group (without instrumentation), curette instrumentation, ultrasonic instrumentation with universal tip and sonic instrumentation with diamond-coated tip. Each sample was instrumented with fifteen strokes. Before and after instrumentation, surface roughness was measured. In addition, the root surface topography was examined after treatment under the scanning electron microscope. RESULTS: Significant statistical differences (p ;0.05). CONCLUSION: The diamond-coated tip with sonic scaler instrumentation and ultrasonic instrumentation produce similar root surface roughness, higher than curette instrumentation.OBJETIVO: O objetivo do presente estudo foi avaliar a rugosidade radicular obtida após instrumentação por aparelho sônico com pontas diamantadas, curetas e ultrassom. MATERIAL E MÉTODOS: Quarenta superfícies radiculares, devidamente polidas e incluídas em resina acrílica, foram dividas em 4 grupos de tratamento: grupo controle (sem instrumentação) e instrumentação com cureta Gracey 5/6, ultrassom ou aparelho sônico com ponta diamantada. Em cada amostra foram realizados 15 movimentos de raspagem. Antes e após esta instrumentação foi utilizado um rugosímetro para a medição da rugosidade radicular. Além disso, a topografia da superfície radicular foi avaliada após o tratamento com microscopia eletrônica de varredura. RESULTADOS: Diferenças estatisticamente significantes (p;0.05). CONCLUSÃO: A instrumentação sônica com pontas diamantadas promove uma rugosidade radicular equivalente à instrumentação com ultrassom, sendo essa rugosidade superior àquela apresentada pela instrumentação manual

Environmental approach of companies within the pulp/paper, metallurgical and sugar/alcohol sectors

As empresas têm presenciado transformações amplas no ambiente em que estão inseridas e, com o intuito de auxiliar no planejamento estratégico das empresas, têm sido desenvolvidos modelos ambientais. O objetivo desse estudo foi avaliar a conduta ambiental de empresas dos setores de Celulose e Papel, Siderúrgico e Sucroalcooleiro, de forma a verificar as suas performances em termos ambientais. Essa análise baseou-se em uma matriz que relaciona as funções gerenciais com um conjunto de indicadores de conduta e performance ambiental, classificando a conduta ambiental das empresas como fraca, intermediária ou forte. As funções gerenciais abordadas nesse modelo são: administração (Geral, Jurídica, Financeira, Recursos Humanos e Compras); Pesquisa e Desenvolvimento; Produção e Manutenção; e Marketing. Dentre os indicadores analisados destacam-se: inserção internacional; origem de capital e localização. As empresas de Celulose e Papel e Siderúrgicas apresentaram uma pontuação média de 54,50 e 51,56 pontos, respectivamente, sendo classificadas com uma conduta ambiental forte. Por outro lado, as empresas sucroalcooleiras apresentaram uma pontuação média de 46,00 pontos, que as classificaram com uma conduta ambiental intermediária. O nível mais elevado de performance ambiental apresentado pelas empresas dos setores de Celulose e Papel e Siderúrgico pode ser atribuído aos seguintes fatores: maior inserção internacional, presença de capital estrangeiro no controle acionário, atuação no mercado internacional e localização dessas empresas nas proximidades dos grandes centros populacionais. As empresas de Celulose e Papel e principalmente as sucroalcooleiras são menos eficientes no atendimento aos requisitos da legislação ambiental, particularmente quanto à conformidade das áreas de preservação permanente e de reserva legal.Companies have been witnessing major changes in their environment and environmental models have been developed aiming to improve their strategic planning. The objective of this study was to examine the environmental approach adopted by companies within the Pulp and Paper, Metallurgical and Sugar and Alcohol sectors, in order to evaluate their environmental performances. The analysis was based on a matrix which relates managerial functions with a set of environmental approaches and performance indicators, classifying the company environmental performance as weak, moderate or strong. The managerial functions approached in this model are: Management (General, Legal Affairs, Finance, Human Resources and Purchasing); Product and Process Development; Production and Maintenance; and Marketing. The analyzed indicators include: international insertion; capital origin and location. The pulp and paper and metallurgical companies obtained average scores of 54.5 and 51.56 points, respectively, being classified as having a strong environmental performance. On the other hand, the sugar and alcohol companies obtained average score of 46 points, being classified as moderate in environmental performance. The high level of environmental performance of pulp and paper and metallurgical companies can be attributed to the following factors: larger international insertion, presence of foreign capital in controlling shares, performance in the international market and company location near large population centers. Pulp and paper and mainly sugar and alcohol companies are less efficient in meeting the requirements of the environmental legislation, particularly those related to the conformity of permanent protected areas and legal reserves

Decision making in the treatment of class III furcation: resective therapy? Extraction? Implant?

The presence of furcation lesions is associated with bone resorption and lack of insertion in the inter-radicular space, and is a condition that considerably increases the risk of dental loss, particularly in the absence of adequate treatment. In this context, the object of some of the therapies is to keep teeth with furcation lesions that are important to dental planning, to re-establish an anatomy that enables the patient to remove dental biofilm from the compromised area. However, the long term maintenance and treatment of molars with Class III furcation lesions continues to be a challenge to dentists during periodontal therapy, since the anatomy of the inter-radicular region makes it difficult for both professionals and patients to gain access to perform adequate and efficient control of dental biofilm. The impossibility of obtaining appropriate decontamination of the area involved during the root scraping process, including by means of surgical access, demands thatdentists have adequate knowledge to determine the correct therapeutic approach during the treatment of teeth with advance inter-radicularbone loss. The aim of the present study was to discuss the treatments available for Class III furcation lesions and relate clinical procedures that could be performed for the treatment of this type of defect

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinibBackground: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib. Objective: To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic-pathological features and therapeutic response. Material and methods: Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor. Results: AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC. Conclusion: AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinibtreated patients with metastatic renal cell carcinoma.this study was supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors. Rui Manuel Reis is recipient of a National Council of Technological and Scientific Development (CNPq) scholarship.info:eu-repo/semantics/publishedVersio

Detection and Quantitative Analysis of Two Independent Binding Modes of a Small Ligand Responsible for DC-SIGN Clustering

DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin receptor (CLRs) present, mainly in dendritic cells (DCs), as one of the major pattern recognition receptors (PRRs). This receptor has a relevant role in viral infection processes. Recent approaches aiming to block DC-SIGN have been presented as attractive anti-HIV strategies. DC-SIGN binds mannose or fucose-containing carbohydrates from viral proteins such as the HIV envelope glycoprotein gp120. We have previously demonstrated that multivalent dendrons bearing multiple copies of glycomimetic ligands were able to inhibit DC-SIGN-dependent HIV infection in cervical explant models. Optimization of glycomimetic ligands requires detailed characterization and analysis of their binding modes because they notably influence binding affinities. In a previous study we characterized the binding mode of DC-SIGN with ligand 1, which shows a single binding mode as demonstrated by NMR and X-ray crystallography. In this work we report the binding studies of DC-SIGN with pseudotrisaccharide 2, which has a larger affinity. Their binding was analysed by TR-NOESY and STD NMR experiments, combined with the CORCEMA-ST protocol and molecular modelling. These studies demonstrate that in solution the complex cannot be explained by a single binding mode. We describe the ensemble of ligand bound modes that best fit the experimental data and explain the higher inhibition values found for ligand

Protocolos de medicação pré e pós-operatória para cobertura radicular combinada com enxerto de tecido conjuntivo.

This trial evaluated the preemptive and postoperative effect of dexamethasone and ibuprofen on prevention of pain/discomfort, edema and interference in daily life in patients undergoing root coverage combined with subepithelial connective tissue graft (CAF + CTG). Twenty patients were randomly assigned as follows: NSAID Group: 400mg Ibuprofen 60 min preemptive + 400mg Ibuprofen postoperative; or SAID Group: 4mg Dexamethasone 60 min preemptive + 4mg Dexamethasone postoperative. The postoperative medication was administered 8 and 16 h post-surgery. Each patient received questionnaires based on a numeric scale (101-point numeric scale rate [NRS-101]) and multiple choice questions (four-point verbal rating scale [VRS-4]) about trans-operative pain/discomfort, hourly for 8 h after surgery and once a day for three days. A Visual Analogue Scale (VAS) for edema and interference in daily life during the 1st, 2nd, 3rd and 7th day was also answered. The degree of anxiety was rated statistically by the Chi-square test. The Mann-Whitney and Friedman tests were used for the other questionnaires. The surgery time and number of analgesic pills consumed were compared using Student’s t-test. Patients who used dexamethasone presented a trend toward less pain when compared to individuals who ingested ibuprofen, with a significant difference observed 3 h after the procedure (p&lt;0.05). The use of dexamethasone also promoted less edema until the 2nd day and lower interference in daily life on the third day when compared with ibuprofen (p&lt;0.05). We concluded that the use of dexamethasone as a preemptive and postoperative medication was more suitable as a drug therapeutic protocol for CAF + CTG.Este estudo avaliou o efeito pré e pós-operatório de dexametasona e ibuprofeno na prevenção de dor / desconforto, edema e interferência na vida diária em pacientes submetidos à cobertura radicular combinada com enxerto de tecido conjuntivo subepitelial (CAF + CTG).&nbsp;Vinte pacientes foram aleatoriamente designados da seguinte forma: Grupo AINE: 400mg de ibuprofeno 60 min preemptivo + 400mg de ibuprofeno no pós-operatório;&nbsp;ou Grupo SAID: 4mg de dexametasona 60 min preemptiva + 4mg de dexametasona pós-operatória.&nbsp;A medicação pós-operatória foi administrada 8 e 16 horas após a cirurgia.&nbsp;Cada paciente recebeu questionários com base em uma escala numérica (escala numérica de 101 pontos [NRS-101]) e questões de múltipla escolha (escala de avaliação verbal de quatro pontos [VRS-4]) sobre dor / desconforto transoperatório, de hora em hora para 8 h após a cirurgia e uma vez por dia durante três dias.&nbsp;Também foi respondida a Escala Visual Analógica (EVA) para edema e interferência na vida diária durante o 1º, 2º, 3º e 7º dia.&nbsp;O grau de ansiedade foi avaliado estatisticamente pelo teste Qui-quadrado.&nbsp;Os testes de Mann-Whitney e Friedman foram usados ​​para os demais questionários.&nbsp;O tempo de cirurgia e o número de comprimidos analgésicos consumidos foram comparados usando o teste t de Student.&nbsp;Pacientes que fizeram uso de dexametasona apresentaram tendência a menos dor quando comparados aos indivíduos que ingeriram ibuprofeno, com diferença significativa observada três horas após o procedimento (p &lt;0,05).&nbsp;O uso de dexametasona também promoveu menos edema até o 2º dia e menor interferência na vida diária no terceiro dia quando comparado ao ibuprofeno (p &lt;0,05)