Trends in ultra-processed food availability and its association with diet-related non-communicable disease health indicators in the Portuguese population.

Broad variations in dietary and physical activity patterns are part of nutritional transition concept. An additional nutritional transition has as main characteristic the change of consumption of processed foods for ultra-processed foods (UPF). This study aims to evaluate trends of UPF availability in Portuguese population and its association with diet-related non-communicable diseases (NCD) health indicators. This ecological study used data from the Household Budget Surveys conducted by the National Statistics Institute each 5 years within a national representative sample of households. The percentage of UPF was calculated based on the total daily amount of food and beverages available per capita (in grams). Data from the years 1990, 1995, 2000 and 2005 were used, which were retrieved from DAFNE-Anemos Software. NCD age-standardised mortality, prevalence and incidence were obtained from the Global Burden of Disease database, for the years 2000, 2005, 2010 and 2015. Between 1990 and 2005, the UPF availability increased from 3·9 % to 13·8 %. Over the years, almost all food and beverages categories increased the UPF availability contribution, mainly noticeable for milk, sugar, cereal and meat products. Positive correlations were observed between UPF availability and digestive diseases both in prevalence (r = 0·062; P = 0·037) and incidence (r = 0·005; P = 0·010) measures. Neoplasms incidence also showed positive correlation with UPF availability (r = 0·002; P = 0·012). Trends in UPF availability in Portugal increased exponentially. At the same time, there is a trend towards a decrease in unprocessed and processed food availability. The Portuguese population should be made aware of the health risks resulting from excessive consumption of UPF.

Treasures from trash in cancer research.

INTRODUCTION: Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets. MATERIALS AND METHODS: Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated. RESULTS: In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found. CONCLUSIONS: These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.

Food Processing: Comparison of Different Food Classification Systems.

The substitution of minimally processed food and culinary home preparations for ready-to-eat products is increasing worldwide, which is overlooked as a cause of concern. The technological developments and the rise in highly processed food availability have introduced the concept of ultra-processed food (UPF). Food classification systems based on processing are now a new basis for epidemiological research. Different results from these classifications might influence conclusions on the population's consumption of UPF or its association with health outcomes. The aim of this study was to compare classification systems and to find out if their results are comparable when evaluating the extent of high/UPF on the overall diet. Portuguese data from the year 2000 was extracted from the DAFNE-AnemosSoft, and 556 food/beverages items were classified according to five systems. The contribution of UPF was calculated as a percentage of total available amount and discrepancy ranges used for comparisons. Results of UPF availability contributions were: NOVA 10.2%; UNC 15.2%; IFPRI 16.7%; IFIC 17.7%; IARC 47.4%. The highest discrepancy ranges were from alcoholic beverages (97.4%), milk/milk products (94.2%), sugar/sugar products (90.1%), added lipids (74.9%), and cereals/cereal products (71.3%). Inconsistencies among classifications were huge and the contribution from highly/UPF presented high discrepancies. Caution must be taken when comparing and interpreting such data.

Ultra-Processed Food Availability and Noncommunicable Diseases: A Systematic Review.

Ultra-processed food (UPF) can be harmful to the population's health. To establish associations between UPF and health outcomes, food consumption can be assessed using availability data, such as purchase lists or household budget surveys. The aim of this systematic review was to search studies that related UPF availability with noncommunicable diseases or their risk factors. PRISMA guidelines were used. Searches were performed in PubMed, EBSCO, Scopus and Web of Science in February 2021. The search strategy included terms related to exposure (UPF) and outcomes (noncommunicable diseases and their risk factors). Studies that assessed only food consumption at an individual level and did not present health outcomes were excluded. Two reviewers conducted the selection process, and a third helped when disagreement occurred. The Newcastle-Ottawa Scale was used to assess the studies' quality; 998 records were analyzed. All 11 eligible studies were ecological and assessed overweight and obesity as a health outcome, only one showed no positive association with UPF availability. Two studies included the prevalence of diabetes as an outcome, however no significant association was found with UPF availability. Studies relating UPF availability and health outcomes are focused on overweight and obesity. It is necessary to further explore the relationship between other health outcomes and UPF availability using purchase or sales data.

ACE2 polymorphisms as potential players in COVID-19 outcome.

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.

Effects of alkaline water intake on gastritis and miRNA expression (miR-7, miR-155, miR-135b and miR-29c).

It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics. METHODS: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months. RESULTS: Endoscopic findings of gastritis were such different (less severe disease), P = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (P = 0.039) and miR-29c (P = 0.039). CONCLUSION: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months.

Hereditary gastric cancer: Three rules to reduce missed diagnoses.

Gastric cancer remains one of the most lethal cancers. The incidence and mortality rates are quite similar. The main reason for the high mortality is diagnosis at advanced stages of disease, when treatment options are poor. One of the supposed strategies to overcome late-stage diagnosis is identifying people at high risk with the aim of establishing rigorous clinical control, including routine endoscopy and biopsies. Hereditary gastric cancer (HGC) syndromes, though representing a sizeable group to monitor for prevention or, at least, for early diagnosis, are apparently extremely rare. The low rate of HGC diagnosis might be related to the low rates of suspicion, insufficient familiarity about clinical diagnosis criteria, and the supposed conditional necessity of a molecular diagnosis. In this review, we will discuss simple measures to increase HGC diagnosis by applying three rules that might provide an opportunity for precision care to benefit the families affected by this disease.

The Small Bowel Cancer Incidence Enigma.

Although the small bowel is a vast organ with a highly proliferative epithelium, the incidence of small bowel cancers is surprisingly low. Many factors could be involved in this unexpected cancer incidence, including difficult access to the exploration of the small bowel mucosa, which might lead to missed diagnoses of non-obstructive and non-bleeding small tumours. Moreover, possible factors that influence the low incidence include more efficient machinery of DNA replication and DNA repair enzymes, peculiarities in microbiota components, competence of the immune system, and the speed of intestinal transit. Importantly, the answer for the enigmatic risk of driver mutations caused by replication errors may be hidden in the small bowel, which is an obscure part of digestive tract that is usually inaccessible by endoscopic or colonoscopic conventional investigations. These observations warrant the necessity of an urgent exploration of small bowel features, including the evaluation of DNA replication controls and expression of DNA repair genes, in order to shed light on these obscure events.

Incidence of weight gain in hospital workers: survival analysis. / Incidência de ganho de peso em trabalhadores de um hospital: análise de sobrevivência.

Weight gain in adult life may be responsible for chronic diseases, and follow-up of this may be a subsidy to avoid these diseases. The objective was to analyze the weight gain and associated factors in workers of a private hospital in the city of Rio de Janeiro. This is a retrospective cohort of 686 workers, who performed at least two occupational health exams (admission and periodic) between 2010 and 2015. The Kaplan-Meier method and the Cox proportional hazards regression model were used. The incidence of weight gain of hospital workers was 22 cases / 100 person-years. The weight gain in workers over 30 years old was 35% lower (p < 0.001) when compared to weight gain in those up to 30 years of age. Regarding schooling, the incidence rates of weight gain among workers at primary and secondary levels were higher, with a magnitude of up to 61%, compared to those at a higher level (p < 0.001); And in the closed sector it was 63% higher when compared to the open sector (p < 0.001). Weight gain is a multifaceted and complex phenomenon, being the work sectors of a hospital unit a strong causer of occurrences of the event.

O ganho de peso na vida adulta pode ser responsável por doenças crônicas, e seu acompanhamento pode ser um subsídio para evitar esses agravos. O objetivo foi analisar o ganho de peso e fatores associados em trabalhadores de um hospital privado no município do Rio de Janeiro. Trata-se de uma coorte retrospectiva com 686 trabalhadores, que realizaram ao menos dois exames de saúde ocupacionais (admissional e periódico) entre os anos de 2010 e 2015. O método de Kaplan-Meier e o modelo de regressão semiparamétrico de riscos proporcionais de Cox foram utilizados. A incidência de ganho de peso dos trabalhadores do hospital foi de 22 casos/100 pessoas-ano. O ganho de peso nos trabalhadores com mais de 30 anos foi 35% menor (p < 0,001), quando comparado ao ganho de peso naqueles de até 30 anos. Em relação à escolaridade, as taxas de incidência de ganho de peso nos trabalhadores de níveis fundamental e médio se apresentaram maiores, com magnitude de até 61%, comparadas aos de nível superior completo (p < 0,001); e no setor de trabalho considerado fechado foi 63% maior quando comparada ao setor aberto (p < 0,001). Ganho de peso é um fenômeno multifacetado e complexo, podendo os setores de trabalho de uma unidade hospitalar contribuir fortemente para a ocorrência do mesmo.

Incidência de ganho de peso em trabalhadores de um hospital: análise de sobrevivência / Incidence of weight gain in hospital workers: survival analysis

Resumo O ganho de peso na vida adulta pode ser responsável por doenças crônicas, e seu acompanhamento pode ser um subsídio para evitar esses agravos. O objetivo foi analisar o ganho de peso e fatores associados em trabalhadores de um hospital privado no município do Rio de Janeiro. Trata-se de uma coorte retrospectiva com 686 trabalhadores, que realizaram ao menos dois exames de saúde ocupacionais (admissional e periódico) entre os anos de 2010 e 2015. O método de Kaplan-Meier e o modelo de regressão semiparamétrico de riscos proporcionais de Cox foram utilizados. A incidência de ganho de peso dos trabalhadores do hospital foi de 22 casos/100 pessoas-ano. O ganho de peso nos trabalhadores com mais de 30 anos foi 35% menor (p < 0,001), quando comparado ao ganho de peso naqueles de até 30 anos. Em relação à escolaridade, as taxas de incidência de ganho de peso nos trabalhadores de níveis fundamental e médio se apresentaram maiores, com magnitude de até 61%, comparadas aos de nível superior completo (p < 0,001); e no setor de trabalho considerado fechado foi 63% maior quando comparada ao setor aberto (p < 0,001). Ganho de peso é um fenômeno multifacetado e complexo, podendo os setores de trabalho de uma unidade hospitalar contribuir fortemente para a ocorrência do mesmo.

Abstract Weight gain in adult life may be responsible for chronic diseases, and follow-up of this may be a subsidy to avoid these diseases. The objective was to analyze the weight gain and associated factors in workers of a private hospital in the city of Rio de Janeiro. This is a retrospective cohort of 686 workers, who performed at least two occupational health exams (admission and periodic) between 2010 and 2015. The Kaplan-Meier method and the Cox proportional hazards regression model were used. The incidence of weight gain of hospital workers was 22 cases / 100 person-years. The weight gain in workers over 30 years old was 35% lower (p < 0.001) when compared to weight gain in those up to 30 years of age. Regarding schooling, the incidence rates of weight gain among workers at primary and secondary levels were higher, with a magnitude of up to 61%, compared to those at a higher level (p < 0.001); And in the closed sector it was 63% higher when compared to the open sector (p < 0.001). Weight gain is a multifaceted and complex phenomenon, being the work sectors of a hospital unit a strong causer of occurrences of the event.

Suicide journey of H. pylori through gastric carcinogenesis: the role of non-H. pylori microbiome and potential consequences for clinical practice.

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.

In vitro assessment of cytotoxic, genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes.

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.

Traps and trumps from adjacent-to-tumor samples in gastric cancer research.

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opportunities to the discovery of cancer biomarkers and molecular targets.

Piwi like RNA-mediated gene silencing 1 gene as a possible major player in gastric cancer.

AIM: To establish a permanent piwi like RNA-mediated gene silencing 1 (PIWIL1) gene knockout in AGP01 gastric cancer cell line using CRISPR-Cas9 system and analyze phenotypic modifications as well as gene expression alterations. METHODS: CRISPR-Cas9 system used was purchased from Dharmacon GE Life Sciences (Lafayette, CO, United States) and permanent knockout was performed according to manufacturer's recommendations. Wound-healing assay was performed to investigate the effect of PIWIL1 knockout on migration capability of cells and Boyden chamber invasion assay was performed to investigate the effect on invasion capability. For the gene expression analysis, a one-color microarray-based gene expression analysis kit (Agilent Technologies, Santa Clara, CA, United States) was used according to the protocol provided by the manufacturer. RESULTS: PIWIL1 gene knockout caused a significant decrease in AGP01 migration capacity as well as a significant decrease in cell invasiveness. Moreover, functional analysis based on grouping of all differentially expressed mRNAs identified a total of 35 genes (5 up-regulated and 30 down-regulated) encoding proteins involved in cellular invasion and migration. According to current literature, 9 of these 35 genes (DOCK2, ZNF503, PDE4D, ABL1, ABL2, LPAR1, SMAD2, WASF3 and DACH1) are possibly related to the mechanisms used by PIWIL1 to promote carcinogenic effects related to migration and invasion, since their functions are consistent with the changes observed (being up- or down-regulated after knockout). CONCLUSION: Taken together, these data reinforce the idea that PIWIL1 plays a crucial role in the signaling pathway of gastric cancer, regulating several genes involved in migration and invasion processes; therefore, its use as a therapeutic target may generate promising results in the treatment of gastric cancer.

GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.

Insights into gastric neuroendocrine tumors burden.

Type 1 gastric neuroendocrine tumors (gNETs) are usually small lesions, restricted to mucosal and sub-mucosal layers of corpus and fundus, with low aggressive behavior, for the majority of cases. Nevertheless, some cases present aggressive behavior. The increasing incidence of gNETs brings together a new relevant problem: how to identify potentially aggressive type 1 gNETs. The challenging problem seems to be finding out signs or features able to predict potentially aggressive cases, allowing a tailored approach, since the involved societies dedicated to provide guidelines for management of these neoplasms apparently failed in producing staging systems able to accurately predict prognosis of these tumors. Additionally, it is also important to try to find out explanations for increasing incidence, as well as to identify potential targets aiming to reach better control of this neoplasia. Here, we discuss potential pathways implicated in aggressive behavior, as well as new strategies to improve clinical management of these tumors.

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines.

AIM: To identify common copy number alterations on gastric cancer cell lines. METHODS: Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS: The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION: The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.

Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer.

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.

The role of piRNA and its potential clinical implications in cancer.

Epigenetic mechanisms work in an orchestrated fashion to control gene expression in both homeostasis and diseases. Among small noncoding RNAs, piRNAs seem to meet the necessary requirements to be included in this epigenetic network due to their role in both transcriptional and post-transcriptional regulation. piRNAs and PIWI proteins might play important roles in cancer occurrence, prognosis and treatment as reported previously. Nevertheless, the potential clinical relevance of these molecules has yet been elucidated. A brief overview of piRNA biogenesis and their potential roles as part of an epigenetic network that is possibly involved in cancer is provided. Moreover, potential strategies based on the use of piRNAs and PIWI proteins as diagnostic and prognostic biomarkers as well as for cancer therapeutics are discussed.