Dynamic variations of the gastric microbiota: Key therapeutic points in the reversal of Correa's cascade.

Correa's cascade is a dynamic process in the development of intestinal-type gastric cancer (GC), and its pathological features, gastric microbiota and interactions between microorganisms and their hosts vary at different developmental stages. The characteristics of cells, tissues and gastric microbiota before or after key therapeutic points are critical for monitoring malignant transformation and early tumour reversal. This review summarises the pathological features of gastric mucosa, characteristics of gastric microbiota, specific microbial markers, microbe-microbe interactions and microbe-host interactions at different stages in Correa's cascade. The markers related to each Correa's cascade point were analysed in detail. We attempted to identify key therapeutic points for early cancer reversal and provide a novel approach to reduce the incidence of GC and improve precise treatment.

Berberine for gastric cancer prevention and treatment: Multi-step actions on the Correa's cascade underlie its therapeutic effects.

Gastric carcinoma (GC) is a complex multifactorial disease occurring as sequential events commonly referred to as the Correa's cascade, a stepwise progression from non-active or chronic active gastritis, to gastric precancerous lesions, and finally, adenocarcinoma. Therefore, the identification of novel agents with multi-step actions on the Correa's cascade and those functioning as multiple phenotypic regulators are the future direction for drug discovery. Recently, berberine (BBR) has gained traction owing to its pharmacological properties, including anti-inflammatory, anti-cancer, anti-ulcer, antibacterial, and immunopotentiation activities. In this article, we investigated and summarized the multi-step actions of BBR on Correa's cascade and its underlying regulatory mechanism in gastric carcinogenesis for the first time, along with a discussion on the strength of BBR to prevent and treat GC. BBR was found to suppress H. pylori infection, control mucosal inflammation, and promote ulcer healing. In the gastric precancerous lesion phase, BBR could reverse mucosal atrophy and prevent lesions in intestinal metaplasia and dysplasia by regulating inflammatory cytokines, promoting cell apoptosis, regulating macrophage polarization, and regulating autophagy. Additionally, the therapeutic action of BBR on GC was partly realized through the inhibition of cell proliferation, migration, and angiogenesis; induction of apoptosis and autophagy, and enhancement of chemotherapeutic drug sensitivity. BBR exerted multi-step actions on the Correa's cascade, thereby halting and even reversing gastric carcinogenesis in some cases. Thus, BBR could be used to prevent and treat GC. In conclusion, the therapeutic strategy underlying BBR's multi-step action in the trilogy of Correa's cascade may include "prevention of gastric mucosal inflammation (Phase 1); reversal of gastric precancerous lesions (Phase 2), and rescue of GC (Phase 3)". The NF-κB, PI3K/Akt, and MAPK signaling pathways may be the key signaling transduction pathways underlying the treatment of gastric carcinogenesis using BBR. The advantage of BBR over conventional drugs is its multifaceted and long-term effects. This review is expected to provide preclinical evidence for using BBR to prevent gastric carcinogenesis and treat gastric cancer.

Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals.

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

Genetic diversity and population structure of Bael [Aegle marmelos (L.) Correa] genotypes using molecular markers in the North-Western plains of India.

Bael is a fruit crop that is extensively distributed throughout South-East Asia and is underutilized in medicine. The potential applications of bael's therapeutic and nutritional qualities in diverse ethnic communities are enormous. This study focuses on evaluating the morpho-pomological and molecular characteristics, utilizing SSR markers, of 80 wild bael genotypes alongside the NB-5 and NB-9 cultivars, derived from the North Western plains of India. Based on the evaluated morpho-pomological features, substantial variations were found between all genotypes. The fruit's inner diameter and pulp weight varied from 4.41 to 11.54 cm and 34.63 to 786.41 g, respectively. Numerous variations in the genotypes were observed in the shell weight/fruit, fruit skull thickness and fruit yield/plant. The bael fruit mucilage's total soluble solids (TSS) and total sugar content varied from 40.10 to 49.60 obrix and 8.11 to 21.17%, respectively. Using ward cluster analysis, the genotypes were divided into two primary clusters. Among the bael genotypes, the population structure analysis identified three subpopulations. SSR markers are used to measure genetic variety; of the 27 polymorphic markers, 17 show allelic diversity between genotypes. Molecular genetic diversity analysis, on the other hand, highlighted the genotypes genetic distinctiveness by classifying them into three major clusters. These findings offer valuable insights into the rich diversity and intricate interactions among the bael genotypes under investigation, paving the way for more strategic future breeding and selection efforts to elevate the quality of this remarkable fruit.

Natural products for gastric carcinoma prevention and treatment: Focus on their antioxidant stress actions in the Correa's cascade.

BACKGROUND: Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS: To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS: NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.

Molecular evolution of intestinal-type early gastric cancer according to Correa cascade.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer.

Objective: Ghrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear. Methods: In this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan-Meier Plotter. Furthermore, R software analysis for GC Correa' cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: We found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC. Conclusions: GHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. AIM OF THE STUDY: The objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. MATERIALS AND METHODS: To study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. RESULTS: The topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. CONCLUSIONS: The current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis.

Carbamoyl phosphate synthetase 1 (CPS1), which is the antigen for the hepatocyte paraffin 1 antibody, exhibits focal immunoreactivity in adenocarcinoma from the gastrointestinal tract, but its expression profiles and roles in gastric cancer (GC) remain largely unknown. The present study aimed to determine the expression pattern and prognostic value of CPS1 in Correa's cascade using tissues from 32 patients with chronic atrophic gastritis with intestinal metaplasia (IM), 62 patients with low- or high-grade intraepithelial neoplasia (IN) and 401 patients with GC. The expression of CPS1 was diffuse and strongly positive in 32 cases (100%) of IM of the glandular epithelium, and gradually downregulated in Correa's cascade, with a strongly positive ratio of 21 (70%) in low-grade IN and 4 (12.5%) in high-grade IN. The levels of CPS1 expression were significantly higher in diffuse-type GC, with 37 (26%) cases strongly positive for CPS1, compared with 14 (8%) in intestinal-type and 11 (13%) cases in mixed-type GC. In intestinal-type GC, CPS1 expression was completely lost in 107 (62%) of cases, which was associated with an advanced Tumor-Node-Metastasis stage (P=0.031) and depth of invasion (P=0.037). Kaplan-Meier analysis suggested that low CPS1 expression levels were independently associated with a short overall survival (OS) time in the three types of GC (P<0.001 in intestinal-type, P=0.003 in diffuse-type and P=0.018 in mixed-type GC). Furthermore, low levels of CPS1 mRNA and high methylation levels in the CPS1 promoter were associated with a short OS time in patients with GC. These results suggested that the expression of CPS1 was progressively downregulated in Correa's cascade, and that CPS1 may serve as a prognostic marker for patients with GC, regardless of tumor type.

Specification and DNA Barcoding of Thai Traditional Remedy for Chronic Kidney Disease: Pikad Tri-phol-sa-mut-than.

The Pikad Tri-phol-sa-mut-than (TS) remedy, a Thai traditional medicine, is officially recorded in Tamra Paetsart Sonkrau Chabub Anurak for its capabilities in treating kidney deficiency. TS remedy is composed of three fruit species-Aegle marmelos (L.) Corrêa., Coriandrum sativum L., and Morinda citrifolia L.-in an equal part by weight. The quality of the raw material is one of the essential factors that can affect the effectiveness and safety of treatment by herbal remedy. The pharmacognostic evaluation and DNA barcode of the three fruit species and TS remedy were performed in this study to authenticate them from contamination, and to provide the scientific database for further uses. Macroscopic and microscopic examination, chemical profile by TLC, and DNA barcoding were employed to positively identify the raw materials bought from the herbal market, especially the powder form. Consequently, the outcomes of this investigation can be used to develop an essential and effective tool for the authentication of crude drugs and herbal remedies.

Modeling of process intensification of biodiesel production from Aegle Marmelos Correa seed oil using microreactor assisted with ultrasonic mixing.

Conventionally, the batch type reactors were used for the production of biodiesel. However, in recent years, the usage of microreactors has started emerging as a significant substitute for biodiesel production due to its higher conversion rate at a short duration. These microreactors have a significantly high surface to volume ratio and high heat-mass transfer rate. The disadvantage of this type of reactors is its low mixing rate of the reagents. This can be overcome with the assistance of ultrasonic mixing. The main objective of this paper is to study the interlaced effect of a continuous flow microreactor and ultrasonic mixing on trans-esterification of Aegle Marmelos Correa seed oil using sodium methoxide catalyst. Results of microreactors with 0.3 mm and 0.8 mm diameter were compared. The effects of process parameters namely, flow rate (2-10 mL/min), reaction temperature (45-65 °C), catalyst amount (0.5-2.5 wt%), oil to methanol molar ratio (1:6-1:18) and ultrasonic mixing time (30-150 s) were studied using response surface methodology (RSM). The biodiesel yield of 98% and 91.8% were obtained for 0.3 mm and 0.8 mm microreactors, respectively. The maximum biodiesel yield observed in 0.3 mm reactor under following optimum conditions: 6.8 mL/min flow rate, 48 °C reaction temperature, 1.3 wt% catalyst, 1:9 oil to methanol molar ratio and 83 s ultrasonic mixing time. The predictive and generalization abilities of RSM and artificial neural network (ANN) models were evaluated and compared. The study showed that ANN and RSM models could predict the yield with an R2 value of 0.9955 and 0.9900 respectively. However, the ANN model predicted the yield with the least mean square error value of 0.00001294, which is much lower than RSM.

Edible fruits from Brazilian biodiversity: A review on their sensorial characteristics versus bioactivity as tool to select research.

The Brazilian flora is very rich in edible fruits but only a fraction of this potential is known and properly used. In this study, we discuss the importance of Brazilian edible fruits using data recovered from the book "Dicionário das plantas úteis do Brasil e das exóticas cultivadas" (Dictionary of Useful Plants of Brazil and Exotic Cultivated), organized by the Portuguese botanist Manoel Pio Corrêa (1874-1934), in 1926. Data from 504 species were recorded from the book and several have attractive and/or sensorial characteristics, as tasty and sweet, that can contribute to stimulating their direct consumption. Only 25% of the recorded fruits have their health benefits determined in studies of bioactivity. A ranking (Priority Index = PI) was constructed in order to know the most promising fruits. Anacardium occidentale, Passiflora edulis and Acrocomia aculeata reached a higher PI. Among the families, Orchidaceae, Verbenaceae, Anacardiaceae and Caryocaraceae have a higher proportion of fruits with higher PI. Besides the health benefits, the market and management of these plants can contribute to biodiversity conservation and improve the income of local populations.

Analysis of gastric and duodenal biopsy results in patients presenting with dyspepsia: a cross-sectional study in a middle eastern population.

OBJECTIVE: Correa's cascade is a 'Model for Gastric Cancer Development' described by Peleyo Correa. The reversibility of Correa's cascade remains debatable. The literature contains insufficient data on the specific stage of the cascade during which Helicobacter pylori is detected, treated, and the effect on prognosis. Herein, we aim to determine the prevalence of various precancerous and cancerous gastric lesions in patients presenting with dyspepsia, the prevalence of gastritis and H. pylori infection, the prevalence of duodenal pathology in patients presenting with dyspepsia, identify the stage of H. pylori detection in relation to Correa's cascade, and investigate a possible relationship between H. pylori and celiac disease. DESIGN: Retrospective cross-sectional study conducted on a middle eastern population at a Lebanese tertiary hospital centre. 1428 patients presenting with dyspepsia underwent gastroscopy with gastric and duodenal biopsies. Variables include age, sex, presence/absence of H. pylori infection, and histopathological analysis of gastric and duodenal biopsies. RESULTS: Being above 40 years of age was associated with increased likelihood of exhibiting abnormal gastric biopsy result. Gastritis and metaplasia were detected more frequently than glandular atrophy (p<0.001) with gastritis being present the most (p<0.001). The presence of H. pylori and the gastric biopsy results were not associated with any of the duodenal biopsy results. CONCLUSION: The burden of H. pylori infection in patients with dyspepsia was high. H. pylori was detected at various precancerous lesions with varying significance. The prevalence of duodenal adenocarcinoma in dyspeptic patients is unexpectedly high. No association between gastric and duodenal pathologies was found.

Premalignant lesions and gastric cancer: Current understanding.

Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer (GC) and its premalignant states from gross histological models to increasingly precise molecular descriptions. In this review we reflect upon the historic approaches to describing premalignant lesions and GC, highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.

Expression profile of circulating microRNAs in the Correa pathway of progression to gastric cancer.

BACKGROUND: Helicobacter pylori infection causes long-term chronic active gastritis, a risk factor for the intestinal and diffuse forms of gastric cancer. Most gastric cancers develop in a stepwise progression from chronic active gastritis to precursor lesions of gastric cancer. The early detection of gastric cancer improves survival. Studies with recent evidence have proposed circulating-microRNAs as biomarkers of cancer. OBJECTIVE: The purpose of this study was to explore the circulating-microRNA profile from H. pylori infection to gastric adenocarcinoma. METHODS: One hundred and twenty-three patients were enrolled and assigned to the discovery or the validation sets. In the discovery phase, circulating-microRNAs were measured by dye-based quantitative polymerase chain reaction and a selection of circulating-microRNAs was validated by probe-based quantitative polymerase chain reaction. A quality control protocol was used. RESULTS: One hundred and sixty-seven circulating-microRNAs were detected. Precursor lesions of gastric cancer and gastric cancer patients showed the downregulation of eight and five circulating-microRNAs, respectively. We further validated the deregulation of miR-196a-5p in precursor lesions of gastric cancer and the deregulation of miR-134-5p, miR-144-3p and miR-451a in gastric cancer. However, circulating-microRNAs exhibited moderate diagnostic performance due to the overlap of circulating-microRNA expression between non-cancer and cancer patients. miR-144-3p/miR-451a expression levels were correlated. Interestingly, these microRNAs are in 17q11.2, a site of rearrangements associated with gastric cancer. CONCLUSION: Circulating-microRNAs are deregulated in precancerous and gastric cancer patients but efforts are needed to improve their diagnostic accuracy.

"A Pedra Fundamental da Eugenia no Brasil": afundação do Ambulatório Rivadávia Corrêa / "The Cornerstone of Eugenics in Brazil": the foundation of the Ambulatório Rivadávia Corrêa

Esta pesquisa investiga como a fundação do Ambulatório Rivadávia Corrêa, polo irradiador da educação higiênica nos subúrbios cariocas, foi noticiada por periódicos, jornais e revistas do período. A hipótese é que o ambulatório ratificou uma política de tratamento que extrapolava o saber psiquiátrico e fazia confluir discursos diversos, tais como republicanismo, trabalho, pobreza e raça. Na análise desse campo de diálogo espera-se compreender a participação do ideário psiquiátrico nas teorias eugênicas e inseri-lo em uma perspectiva mais ampla, adequada ao conjunto de instrumentos de regulação social que precisaram ser construídos (ou reconstruídos) após o fim da escravidão no Brasil. A pesquisa foi realizada sobre fontes primárias, que compõem o acervo da plataforma Hemeroteca Digital, da Biblioteca Nacional. Como instrumento de análise desse material se fez uso do conceito de Marcador Social, compreendido como o conjunto de diferenças socialmente construídas que se somam na produção das desigualdades ou hierarquias.

This research investigates how the foundation of Ambulatório Rivadávia Corrêa, a hub for hygienic education in the suburbs of Rio de Janeiro, was reported by journals, newspapers and magazines of the period. The hypothesis is that the clinic ratified a treatment policy that extrapolated psychiatric knowledge and brought together diverse discourses, such as republicanism, work, poverty and race. In the analysis of this field of dialogue, it is expected to understand the participation of psychiatric ideas in eugenic theories, and insert it in a broader perspective, adequate to the set of instruments of social regulation that had to be built (or rebuilt) after the end of slavery in Brazil. The research was carried out on primary sources, which make up the collection of the Hemeroteca Digital platform of the National Library. As a tool for analyzing this material, the concept of Social Marker was used, understood as the set of socially constructed differences that add up to the production of inequalities or hierarchies.

Two new cytotoxic furoquinoline alkaloids isolated from Aegle marmelos (Linn.) Correa.

Two new cytotoxic furoquinoline alkaloids were isolated from the leaves of Aegle marmelos (Linn.) Correa; one from the total alkaloidal fraction (acid/base shake-out method) of the CHCl3 extract and identified as 7,8-dihydroxy-4-hydrofuroquinoline and named trivially as Aegelbine-A. The other new alkaloid isolated from the pet. ether extract and identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline and named trivially as Aegelbine-B, together with a known alkaloid; aegeline and a known phenolic acid; ρ-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and HR-ESI/MS. The cytotoxic activity of the isolated compounds was evaluated in vitro against HepG-2, PC3, A549 and MCF-7 cell lines. The obtained results revealed promising activity with structure-based relationship which is discussed briefly.

Case study: what did Rafael Correa say? Comparing political attention across 10 years of the Ecuadorian president's discourses / Estudio de caso: ¿qué dijo Rafael Correa? Comparando la atención política en 10 años de discursos del presidente ecuatoriano / Estudo de caso: o que Rafael Correa disse? Comparando a atenção política em 10 anos dos discursos do presidente equatoriano

Abstract The "citizen revolution" was a political project executed mainly between 2007 and 2016 by the former president of the Republic of Ecuador, Rafael Correa Delgado, under the paradigm of 21st century socialism. The main characteristic of this project was to introduce a new political agenda to the country that was differentiated from past agendas, by focusing on issues such as the recognition of new rights, improvements to education, instituting a new economic model, and strengthening government and sovereignty, among others. Under this context, this work aims to analyze the political attention of the ex-president, explaining why some issues are more important than others, and why they varied over time. Based on a conceptual framework that takes ideas from the agenda-setting theory, the areas on which the political agenda concentrates are measured by the Shannon entropy index, and its various changes are explained as the results of preferences, institutional factors, and external events. The analysis is based on extensive database analyses of 10 years (covering Rafael Correa's presidency) of government speeches, which are coded according to the methodology of the Comparative Agendas Project (CAP). To the best of our knowledge, this paper is the first work to apply the CAP methodology in Ecuador.

Resumen La "revolución ciudadana" fue el proyecto político ejecutado principalmente por el expresidente de la República del Ecuador, Rafael Correa Delgado, bajo el paradigma del socialismo del siglo XXI, entre 2007 y 2016. Este proyecto se caracterizó por establecer una nueva agenda política en el país, diferenciándose de las pasadas, enfocándose en temas como el reconocimiento de nuevos derechos, mejora de la educación, propuesta un nuevo modelo económico y el fortalecimiento del gobierno y la soberanía entre otros. Bajo este contexto, este trabajo tiene como objetivo analizar la atención política de la agenda del expresidente de la república, explicar por qué algunos temas son más importantes que otros y por qué hay variaciones en ellos a lo largo del tiempo. Con base en un marco conceptual que toma ideas de la teoría del establecimiento de la agenda, se mide la concentración de la agenda política a través del índice de entropía de Shannon y se explican los diferentes cambios en ella a raíz de las preferencias, las fricciones institucionales y los eventos externos. El análisis se basa en extensas bases de datos sobre 10 años de discursos del gobierno (presidencia de Rafael Correa), que están codificados de acuerdo con la metodología del Proyecto de Agendas Comparadas (PAC). Por lo que conocemos, este es el primer trabajo que aplica esta metodología en Ecuador.

Resumo A "revolução cidadã" foi o projeto político realizado principalmente pelo ex-presidente da República do Equador, Rafael Correa Delgado, sob o paradigma do socialismo do século XXI entre 2007 e 2016. Esse projeto foi caracterizado por estabelecer uma nova agenda política no país, diferenciando-se do passado, concentrando-se em questões como reconhecimento de novos direitos, melhoria da educação, proposta de um novo modelo econômico e fortalecimento do governo e da soberania, entre outros. Nesse contexto, este trabalho tem como objetivo analisar a atenção política na agenda do ex-presidente da república, explicar por que algumas questões são mais importantes que outras e por que há variações nelas ao longo do tempo. Com base em uma estrutura conceitual que retira ideias da teoria da definição da agenda, a concentração da agenda política é medida através do índice de entropia de Shannon e as diferentes mudanças nele são explicadas como resultado de preferências, atritos institucionais e eventos externos. A análise é baseada em extensas bases de dados de 10 anos de discursos governamentais (presidência de Rafael Correa), codificados de acordo com a metodologia do Projeto de agendas comparativas (PAC). Até onde sabemos, este é o primeiro trabalho que aplica essa metodologia no Equador.

In-vitro anti-inflammatory and mosquito larvicidal efficacy of nickel nanoparticles phytofabricated from aqueous leaf extracts of Aegle marmelos Correa.

In recent years there is a tremendous growth in the interdisciplinary world of nanotechnology across the globe and emergence of its potential applications remains as a big revolution to the industry. Fusion of green nanotechnology and medicine represents one of the major breakthroughs of modern science with the aim of developing nanomaterials for diagnosis, treatment, prevention of various diseases and overall improving health for the beneficial of mankind. In the present study phytofabrication of nickel nanoparticles (nickel NPs) was carried out by using indigenous Aegle marmelos Correa aqueous leaf extracts as a reducing, stabilizing and capping agents. Nickel NPs were characterized by UV-spectroscopy, FTIR, XRD, SEM, AFM and TGA studies. Phytosynthesis of nickel NPs was monitored both at room temperature (25°C) and at 60°C for 5h. The green synthesis of triangular shape nickel NPs phytofabricated from A. marmelos Correa aqueous leaf extracts having face centered cubic structure showing an average particle size of 80-100nm which is in consistent with the particle size calculated by XRD Scherer equation. We further explored and compared nickel NPs of A. marmelos Correa with crude leaf extracts of A. marmelos Correa for its in-vitro anti-inflammatory and mosquito larvicidal efficacy against three blood feeding parasites. The results obtained clearly gives an idea that nickel NPs of A. marmelos Correa (NiNPs of AmC) possess an enhanced anti-inflammatory and larvicidal activity when compared to crude leaf extracts of A. marmelos Correa.

Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats.

OBJECTIVE: To evalueate hepatoprotective effects Feronia elephantum (F. elephantum) correa against thioacetamide (TA) induced liver necrosis in diabetic rats. METHODS: Male wistar rats were made diabetic with alloxan (160 mg/kg) on day 0 of the study. They were intoxicated with hepatotoxicant (thioacetamide, 300 mg/kg, ip) on day 9 of study to produce liver necrosis. Effects of 7 day daily once administration (day 2 to day 9) of EF (400 and 800 mg/kg, po) were evaluated on necorosis of liver in terms of mortality, liver volume, liver weight, serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT), and histopathology of liver sections (for signs of necorosis and inflammation) on day-9 of the study. Separate groups of rats with treated only with alloxan (DA control), thioacetamide (TA control) and both (TA+DA control) were maintained. RESULTS: FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight, volume and serum glucose levels. CONCLUSIONS: FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM.