Gastric Cancer and Angiogenesis: Is VEGF a Useful Biomarker to Assess Progression and Remission?

Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: "Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]". A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.info:eu-repo/semantics/publishedVersio

Immunoscore and Microbiome in Colorectal Cancer: What’s New?

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world, accounting for about 1.4 million new cases and almost 700,000 deaths in 2012. The clinical outcome and the tumor progression are now considered the result of a balance between the invasiveness of the tumor and the immune response of the patient against the tumor. The immune system has the ability to control and shape cancer through a mechanism called immunoediting, which include elimination, equilibrium, and escape. The consensus Immunoscore is a scoring system that outlines the density of CD3+ and CD8+ T-cell effectors existent in the tumor and its invasive margin. The pre-existing intra-tumoral immunity could be enhanced and activated by immunotherapy. Immunoscore could be a good prognostic marker, by identifying patients at high risk of tumor recurrence and stratifying patients who could benefit from adjuvant therapies. Human surfaces and cavities are populated by numerous microbial communities, and they play an indispensable role in human health, as they interact with the immune system. The authors made a literature revision concerning the role of Immunoscore and microbiome in colorectal cancer

Risk factors for falls in the community: based on self-report of elderly persons

Introduction: Several studies have shown independent risk factors for falling among community older people. However, there is few researches showing the importance of older person’s perception of their own fall risk. Aims: The study purpose was to identify independent risk factors for falls and to explore predictive factors related to the occurrence of falls in community-dwelling older people. Method: A cross-sectional study was conducted from January to April 2015. All data were based on self-report of older persons. An study-specific questionnaire was used. Univariate and logistic regression analyses were used. Results: The sample comprised 562 men and 760 women. Among the participants, 24.5% reported having had falls in the previous six months, scoring a total of 467 falling events. Of the individuals who had fallen, 36.8% had experienced recurrent falls. The risk of fall was nearly twice as high in women than in men (OR=1.85; 95% CI: 1.40-2.43). Being 75 years old or older was associated with an increased risk of falling compared with being 65-74 years old (OR=2.38; 95% CI:1.82-3.11). The elderly who had fallen reported injuries (48.3%) associated with falls, and 36% required health care. Conclusion: Six independent risk factors for falling into the community dwelling older people were identified, some of which are potentially modifiable.info:eu-repo/semantics/publishedVersio

IMPACTO DA GORDURA VISCERAL NO PROGNÓSTICO DA CIRURGIA DO CANCRO PERI-AMPOLAR

Periampullary cancers are located up to a maximum distance of 2 cm from the duodenal papilla, with pancreatic cancer being the most common. Despite advances in surgical technique, survival rates remain low, making it essential to identify prognostic factors. Visceral obesity has been identified as a risk factor for cancer development, but its influence on the morbidity and mortality of operated patients remains controversial. This study aims to identify an association between the presence of preoperative visceral obesity and an increased risk of postoperative morbimortality in patients with periampullary cancers at Hospital de Braga. The sample includes 44 patients with periampullary cancers who underwent surgery with a curative intention between January/2011 and April/2018. The area of visceral fat was measured using the ImageJ software. Statistical analysis was performed using the SPSS software version 25. Visceral fat was not implicated in longer hospital stay or postoperative complications. The survival analysis showed no differences in disease-free survival at 1 year (p = 0.121) and 5 years (p = 0.222) or in overall survival at 1 year (p = 0.163) and 5 years (p = 0.053) between groups. Our data suggest that preoperative visceral obesity is not a risk factor for greater postoperative morbidity and mortality in individuals with periampullary cancers. Despite the reduced sample, this study evaluates visceral obesity in four types of tumors with many similar characteristics. Additional studies with larger samples are needed to confirm our observations.Os tumores periampulares estão localizados a uma distância máxima de 2 cm da papila duodenal, sendo a neoplasia mais comum do pâncreas. Apesar dos avanços da técnica cirúrgica, as taxas de sobrevivência permanecem baixas, sendo fundamental a identificação de fatores determinantes do prognóstico. A obesidade visceral tem sido identificada como fator de risco para o desenvolvimento do cancro, mas a sua influência na morbimortalidade pós-operatória permanece controversa. Este estudo teve como objetivo explorar a associação entre a presença de obesidade visceral pré-operatória e o risco de morbimortalidade pós-operatória em indivíduos com cancro periampular no Hospital de Braga. A amostra é constituída por 44 indivíduos com  cancro periampular, submetidos a cirurgia com intenção curativa, entre janeiro de 2011 e abril de 2018. A área de gordura visceral foi medida com recurso ao software ImageJ. A análise estatística foi realizada com o software SPSS versão 25. A gordura visceral não se associou ao maior tempo de internamento ou complicações pós-operatórias. A análise de sobrevivência não revelou diferenças no tempo livre de doença a 1 ano (p = 0,121) ou a 5 anos (p = 0,222), nem na sobrevida global a 1 ano (p = 0,163) ou a 5 anos (p = 0,053) entre os grupos. Os dados sugerem que a obesidade visceral pré-operatória não é fator de risco para maior morbimortalidade pós-operatória em indivíduos com cancro periampular. Apesar da amostra reduzida, este estudo avalia a obesidade visceral em quatro tipos de tumores com muitas características semelhantes. Estudos adicionais com amostras maiores são necessários para confirmar as nossas observações

Reconstrução do ligamento cruzado anterior com duplo feixe versus feixe único: estudo experimental

OBJECTIVE: To test an intra-articular reconstruction of the anterior cruciate ligament of the knee in 10 human cadavers by replacing 2 anterior cruciate ligament bundles, with the purpose of producing a surrogate that would be structurally more similar to the anatomy of the anterior cruciate ligament and would provide the knee with more stability. METHODS: We reconstructed the anteromedial and posterolateral bundles using a quadriceps muscle tendon graft that included a patellar bone segment. The anteromedial bundle was replaced in 10 knees (5 right and 5 left knees from different cadavers) by a quadriceps-bone tendon graft, and the anteromedial and posterolateral bundles were replaced in the matching pairs of these knees. In the latter, the bone segment was fixed to the tibia, and the tendinous portion of the graft was divided longitudinally creating two 5-mm wide bundles that were inserted individually into the femur through 2 independent bone tunnels. Then, the knees were tested mechanically to evaluate the tibial anterior dislocation in relation to the femur, as well as the rigidity of the graft. The control group was formed by the knees with intact anterior cruciate ligaments, before being resected to be reconstructed. RESULTS: The results obtained did not show superiority of double-bundle reconstruction over single-bundle reconstruction, and neither technique provided the knee with the same stability and rigidity of the intact anterior cruciate ligament. CONCLUSION: Our hypothesis, based on the anatomy and biomechanics of the knee, that reconstruction of the anterior cruciate ligament using 2 bundles would result in a more anatomic reconstruction and provide better containment of the anterior tibial translation was not supported by the results of this study.OBJETIVO: Testar uma técnica de reconstrução intra-articular do ligamento cruzado anterior do joelho em 10 cadáveres humanos com substituição de dois feixes do ligamento cruzado anterior, com objetivo de produzir um substituto estruturalmente mais semelhante à anatomia do ligamento cruzado anterior e que conferisse maior estabilidade ao joelho. MÉTODOS: Os feixes ântero-medial e póstero-lateral foram reconstruídos com um enxerto de tendão do músculo quadríceps da coxa, incluindo um segmento ósseo patelar. Dez joelhos (cinco direitos e cinco esquerdos de cadáveres diferentes) tiveram o feixe ântero-medial substituído por um enxerto de tendão quadricipital-osso e, nos pares desses joelhos, foram substituídos o feixe ântero-medial e o póstero-lateral. Nestes últimos, o segmento ósseo foi fixado na tíbia e a parte tendinosa do enxerto foi dividida longitudinalmente, dando origem a dois feixes de 5 mm de largura, que foram inseridos separadamente no fêmur através de dois túneis ósseos independentes. Os joelhos foram então submetidos a ensaios mecânicos, nos quais avaliamos o deslocamento anterior da tíbia em relação ao fêmur e a rigidez do enxerto. Os joelhos com ligamento cruzado anterior íntegro, antes de sua ressecção para a realização das reconstruções, formaram o grupo controle. RESULTADOS: Os resultados obtidos não mostraram superioridade da reconstrução com duplo feixe sobre a reconstrução com feixe único e nenhuma delas conferiu ao joelho a mesma estabilidade e rigidez do ligamento cruzado anterior íntegro. CONCLUSÃO: Apesar de encontrarmos na anatomia e na biomecânica do joelho razões para procurarmos reconstruir o ligamento cruzado anterior com dois feixes, no intuito de tornar a sua reconstrução mais anatômica, proporcionando uma melhor contenção da translação anterior da tíbia, não conseguimos, com os nossos resultados, justificar a utilização da técnica estudada

Fluorinated beta-sheet breaker peptides

The aggregation of amyloid-beta peptide (Ab) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease. We synthesized peptides containing fluorinated amino acids and studied their effect on the Ab aggregation. The peptides were based on the sequence LVFFD, in which valine was substituted by either 4,4,4-trifluorovaline or 4-fluoroproline, or the phenylalanine at position 3 was replaced by 3,4,5-trifluorophenylalanine. Our results demonstrate that fluorination of the hydrophobic residue valine or phenylalanine is effective in preventing the Ab aggregation. This study opens up the possibility of using new sequences based on fluorinated amino acids to inhibit the amyloid- fibril formation

Inflamation and oxidative stress : The molecular connectivity between insulin resistance, obesity and Alzheimer\u27s disease

Type 2 diabetes (T 2 DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T 2 DM) and decreased action of insulin are central to the development and progression of both T 2 DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T 2 DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic in flammatory response and oxidative stress associated with T 2 DM, amyloid- ! (A ! ) protein accumulation, and mitochondrial dysfunction link T 2 DM and AD

Cynara cardunculus: Use in Cheesemaking and Pharmaceutical Applications

Cynara cardunculus L. is the most widespread species of Cynara genus (f. Asteraceae). This herbaceous perennial plant is native to the Mediterranean region and invasive in other parts of the world, growing naturally in harsh habitat conditions. There are three subspecies: globe artichoke; cultivated cardoon and the progenitor of the two, the wild cardoon. The culture of Cynara cardunculus L. follows an annual growth cycle, emerging in autumn and harvesting in summer. Cynara cardunculus has been considered as a multi-purpose crop due to its relevant biochemical profiles. Inflorescences have been used as food, whereas leaves are a rich source of bioactive compounds. Consequently, larger plants without spines have been selected for technological purposes. Due to its high cellulose and hemicellulose content, the lignocellulosic fraction has been used as solid biofuel, biogas and bioethanol. Both pulp fibers production and seeds oil are suitable for biodiesel production. Over the centuries, the inflorescence pistils of Cynara cardunculus L. have been widely used for cheesemaking. The present chapter gives an overview of the Cynara cardunculus L. emphasizing recent knowledge regarding the use, conservation, preparation and application of Cynara cardunculus in ovine milk cheesemaking, as well as other biotechnological applications

Characterization of Cynara cardunculus L. flower from Alentejo as a coagulant agent for cheesemaking

This work was supported by the project ValBioTecCynara (ALT2003-0145- FEDER-000038) - Economic valorisation of Cardoon (Cynara cardunculus): study of natural variability and biotechnological applications), cofinanced by FEDER under the Alentejo 2020 Program.The cardoon (Cynara cardunculus L.) is a mandatory vegetable coagulant for certain Protected Designation of Origin Portuguese cheeses. It grows wild in Portugal and is used without any type of control regarding flower picking or extract preparation, representing some uncertainty in cheese manufacture. The variability in technological properties, in the context of traditional cheese manufacture, of cardoon flower ecotypes from the Alentejo region was evaluated, including milk clotting and proteolytic activities, coagulation properties and potential cheesemaking yield of flower extracts. Multivariate statistics highlighted the variability of flower properties for cheesemaking, but allowed the aggregation of the ecotypes into five groups under the major influence of milk clotting activity and effect on gel firmness and micellar aggregation rate, followed by proteolytic activity. These differences may have an impact on cheese properties and therefore can allow the selection of cardoon flower for the manufacture of different types of cheese.publishersversionpublishe

Identification of animal hosts of Fort Sherman virus, a New World zoonotic orthobunyavirus

An orthobunyavirus termed Fort Sherman virus (FSV) was isolated in 1985 from a febrile US soldier in Panama, yet potential animal reservoirs remained unknown. We investigated sera from 192 clinically healthy peri-domestic animals sampled in northeastern Brazil during 2014–2018 by broadly reactive RT-PCR for orthobunyavirus RNA, including 50 cattle, 57 sheep, 35 goats and 50 horses. One horse sampled in 2018 was positive (0.5%; 95% CI, 0.01–3.2) at 6.2 × 103 viral RNA copies/mL. Genomic comparisons following virus isolation in Vero cells and deep sequencing revealed high identity of translated amino acid sequences between the new orthobunyavirus and the Panamanian FSV prototype (genes: L, 98.8%; M, 83.5%; S, 100%), suggesting these viruses are conspecific. Database comparisons revealed even higher genomic identity between the Brazilian FSV and taxonomically unassigned Argentinian mosquito- and horse-derived viruses sampled in 1965, 1982 and 2013 with only 1.1% maximum translated amino acid distances across viral genes, suggesting the Argentinian viruses were also distinct FSV strains. The Panamanian FSV strain was an M gene reassortant relative to all Southern American FSV strains, clustering phylogenetically with Cache Valley virus (CVV). Mean dN/dS ratios among FSV genes ranged from 0.03 to 0.07, compatible with strong purifying selection. FSV-specific neutralizing antibodies occurred at relatively high end-point titres in the range of 1:300 in 22.0% of horses (11 out of 50 animals), 8.0% of cattle (4/50 animals), 7.0% of sheep (4/57 animals) and 2.9% of goats (1/35 animals). High specificity of serologic testing was suggested by significantly higher overall FSV-specific compared to CVV- and Bunyamwera virus-specific end-point titres (p = .009), corroborating a broad vertebrate host range within peri-domestic animals. Growth kinetics using mosquito-, midge- and sandfly-derived cell lines suggested Aedes mosquitos as potential vectors. Our findings highlight the occurrence of FSV across a geographic range exceeding 7,000 km, surprising genomic conservation across a time span exceeding 50 years, M gene-based reassortment events, and the existence of multiple animal hosts of FSV