The emerging role of piwi-interacting rnas (Pirnas) in gastrointestinal cancers: An updated perspective
Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways’ deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
MicroRNAs as Potential Biomarkers of Environmental Exposure to Polycyclic Aromatic Hydrocarbons and Their Link with Inflammation and Lung Cancer
Exposure to atmospheric air pollution containing volatile organic compounds such as polycyclic aromatic hydrocarbons (PAHs) has been shown to be a risk factor in the induction of lung inflammation and the initiation and progression of lung cancer. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules of ~20–22 nucleotides that regulate different physiological processes, and their altered expression is implicated in various pathophysiological conditions. Recent studies have shown that the regulation of gene expression of miRNAs can be affected in diseases associated with outdoor air pollution, meaning they could also be useful as biomarkers of exposure to environmental pollution. In this article, we review the published evidence on miRNAs in relation to exposure to PAH pollution and discuss the possible mechanisms that may link these compounds with the expression of miRNAs. © 2023 by the authors.
Role of biochemical markers in the monitoring of covid-19 patients
COVID-19 is an infectious disease caused by the SARSCoV- 2 virus, which has given rise to a global sanitary emergency. The clinical characteristics of COVID-19 are varied and can range from an asymptomatic infection to a mild to severe pneumonia. Recent studies have shown that different laboratory parameters become altered in these patients, and as such are useful as biomarkers to assess the progression of the disease and categorize patients that may present a severe and/or fatal clinical condition. This review analyzes biochemical and immunological markers that become altered in COVID-19 patients and their impact on different organs at a hepatic, cardiac, renal and pancreatic level, as well as markers of inflammation, analyzing their implications in the evolution of the disease.
Exploring the Genetic Diversity of Epstein–Barr Virus among Patients with Gastric Cancer in Southern Chile
The Epstein–Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein–Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile. © 2023 by the authors.
Long Non-Coding RNAs (lncRNAs) as Regulators of the PI3K/AKT/mTOR Pathway in Gastric Carcinoma
Gastric cancer (GC) represents ~10% of the global cancer-related deaths, increasingly affecting the younger population in active stages of life. The high mortality of GC is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not guide the patient management adequately, thereby new and more reliable biomarkers and therapeutic targets are still needed for this disease. RNA-seq technology has allowed the discovery of new types of RNA transcripts including long non-coding RNAs (lncRNAs), which are able to regulate the gene/protein expression of many signaling pathways (e.g., the PI3K/AKT/mTOR pathway) in cancer cells by diverse molecular mechanisms. In addition, these lncRNAs might also be proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in GC. This review describes important topics about some lncRNAs that have been described as regulators of the PI3K/AKT/mTOR signaling pathway, and hence, their potential oncogenic role in the development of this malignancy. © 2023 by the authors.
Anthocyanin-Rich Extracts of Calafate (Berberis microphylla G. Forst.) Fruits Decrease In Vitro Viability and Migration of Human Gastric and Gallbladder Cancer Cell Lines
Currently, gastric cancer (GC) and gallbladder cancer (GBC) constitute important causes of human deaths related to cancer worldwide. In the last years, several researches are focused on the role of dietary compounds in preventing cancers. The consumption of fruits with high antioxidants, mainly anthocyanins, represents a good option to reduce the risk of chronic human diseases. Calafate (Berberis microphylla G. Forst.) berries, recognized by their remarkable antioxidant properties and high content of anthocyanins, appear as a new alternative to treat degenerative diseases of public interest. The present work was aimed to evaluate the impact of crude and anthocyanin-rich extracts from Calafate fruits on in vitro cell viability and migration capacity of gastric (AGC) and gallbladder (G415) human cancer cell lines, as related with their antioxidant properties. Crude and anthocyanin-rich extracts were obtained from fruits of Calafate grown under field conditions in the south of Chile. Antioxidants, phenols, anthocyanins, and anthocyanidins were determined. In vitro cell viability and migration of AGS and G415 human cancer cell lines at different concentrations of extracts (25– 800 μg mL−1 ) were determined. Anthocyanin-rich extracts of Calafate berries showed comparable antioxidant activity (up to 1200 μg Trolox eq. g−1 DW), slightly lower total phenolic content (12%), but higher total anthocyanin content (25%) compared to the crude extract. The major anthocyanidin molecule detected in both extracts was delphinidin, followed by malvidin, and low concentrations of petunidin, cyanidin, and peonidin. As expected, all of these compounds were detected in higher levels in anthocyanin-rich extracts (up to 2-fold). Noteworthy, our study revealed that Calafate fruit extracts strongly decrease in vitro viability and migration capacity of gastric carcinoma (AGC model) and gallbladder carcinoma (G415 model) human cell lines; however, the anthocyanin-rich extract displayed higher inhibitory effects (up to 70%) compared to crude extracts. These findings allow suggesting that the in vitro antiproliferative potential of Calafate fruit extract is strongly related to the anthocyanin concentration, especially delphinidin.
The ERK/MAPK pathway is overexpressed and activated in gallbladder cancer
Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues. In addition, protein expression analysis by western blot for ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3 were performed in seven GBC cell lines (GB-d1, G415, NOZ, OCUG-1, TGBC-1, TGBC-2 and TGBC-24). A higher ERK1/2 and p-ERK1/2 expression was found in GBC tissues compared to chronic cholecystitis (CC) tissues (P < 0.001). However, neither significant differences in overall survival nor significant associations with any of the clinicopathological features were found by comparing low and high expression of both ERK1/2 and p-ERK1/2. Western blot analysis of seven GBC cell lines showed that, in general, GB-d1, G415 and NOZ cells evidenced a strong expression of ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3. Therefore, ERK1/2 and p-ERK1/2 seem to be important in the development of GBC and GB-d1, G415 and NOZ cell lines may be used as experimental models for further in vitro and in vivo studies that help to decipher the role of MAPK/ERK pathway in gallbladder carcinogenesis.
A reliable Epstein-Barr Virus classification based on phylogenomic and population analyses
REFERENCE INTERVALS OF BIOCHEMICAL PARAMETERS IN CHILEAN ADULTS
Background: Establishing reference intervals (RIs) in clinical laboratories is essential, as these can vary due to inter-individual variability as well as the analytical methods used. The purpose of this study was to determine RIs for markers and ratios biochemical in apparently healthy Chilean adults. Methods: A sample of 1,143 data was selected from the Universidad Católica de Temuco, Clinical Laboratory database, La Araucanía Region, Chile, which were analysed by sex. The Tukey’s Fences was used to detect outliers and the RIs were established using the non-parametric method. Results: The RIs obtained for the female sex were: Urea 2.48–7.35 mmol/L, AST 0.20–0.69 mkat/L, ALT 0.13–1.12 mkat/L, Alkaline Phosphatase 0.83–2.5 mkat/L, Total Bilirubin 3.5–17.3 mmol/L, Direct Bilirubin 1.5–4.9 mmol/L, Uric Acid 148–362 mmol/L and Total Proteins 66.3–80.3 g/L and for males: Urea 3.28–8.17 mmol/L, AST 0.22–0.80 mkat/L, ALT 0.18–1.9 mkat/L, Alkaline Phosphatase 0.93–2.33 mkat/L, Total Bilirubin 4.58–24.0 mmol/L, Direct Bilirubin 1.9–7.5 mmol/L, Uric Acid 202–458 mmol/L and Total Proteins 67.4–83 g/L. The FIB-4 and APRI index presented a range of 0.2–1.6 and 0.12–0.5 respectively (in both genders) and the AST/ALT index was 0.5–2 in women and 0.38–1.66 in men. Conclusion: A panel of RIs for locally-relevant biochemical parameters has been established, this study being the first to be carried out in our country. When comparing these results with other studies and those reported by reagent manufacturers, some differences were observed. This study thus contributes to increase the reliability in the interpretation of laboratory results and therefore to the clinical management of patients. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.
Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer
Gallbladder cancer (GBC) is an aggressive neoplasm that in an early stage is generally asymptomatic and, in most cases, is diagnosed in advanced stages with a very low life expectancy because there is no curative treatment. Therefore, understanding the early carcinogenic mechanisms of this pathology is crucial to proposing preventive strategies for this cancer. The main risk factor is the presence of gallstones, which are associated with some environmental factors such as a sedentary lifestyle and a high-fat diet. Other risk factors such as autoimmune disorders and bacterial, parasitic and fungal infections have also been described. All these factors can generate a long-term inflammatory state characterized by the persistent activation of the immune system, the frequent release of pro-inflammatory cytokines, and the constant production of reactive oxygen species that result in a chronic damage/repair cycle, subsequently inducing the loss of the normal architecture of the gallbladder mucosa that leads to the development of GBC. This review addresses how the different risk factors could promote a chronic inflammatory state essential to the development of gallbladder carcinogenesis, which will make it possible to define some strategies such as anti-inflammatory drugs or public health proposals in the prevention of GBC. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.