Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

EZH2 as a potential therapeutic target for gastrointestinal cancers.

Gastrointestinal (GI) cancers continue to be a major cause of mortality and morbidity globally. Understanding the molecular pathways associated with cancer progression and severity is essential for creating effective cancer treatments. In cancer research, there is a notable emphasis on Enhancer of zeste homolog 2 (EZH2), a key player in gene expression influenced by its irregular expression and capacity to attach to promoters and alter methylation status. This review explores the impact of EZH2 signaling on various GI cancers, such as colorectal, gastric, pancreatic, hepatocellular, esophageal, and cholangiocarcinoma. The primary function of EZH2 signaling is to facilitate the accelerated progression of cancer cells. Additionally, EZH2 has the capacity to modulate the reaction of GI cancers to chemotherapy and radiotherapy. Numerous pathways, including long non-coding RNAs and microRNAs, serve as upstream regulators of EZH2 in these types of cancer. EZH2's enzymatic activity enables it to attach to target gene promoters, resulting in methylation that modifies their expression. EZH2 could be considered as an independent prognostic factor, with increased expression correlating with a worse disease prognosis. Additionally, a range of gene therapies including small interfering RNA, and anti-tumor agents are being explored to target EZH2 for cancer treatment. This comprehensive review underscores the current insights into EZH2 signaling in gastrointestinal cancers and examines the prospect of therapies targeting EZH2 to enhance patient outcomes.

Validation of thoracic injury rule out criteria as a decision instrument for screening of chest radiography in blunt thoracic trauma.

BACKGROUND: Thoracic injury rule out criteria (TIRC) were first introduced as a decision instrument for selective chest radiography in blunt thoracic trauma in 2014. However, the validity of this model has not been assessed in other studies. In this regard, the present survey evaluates the validity of TIRC model in a multi-center setting. METHODS: In this cross-sectional study, clinical presentations and chest radiograms of multiple trauma patients referring to 6 educational hospitals in Iran were evaluated. Data were gathered prospectively during 2015. In each center, data collection and interpretation of radiograms were conducted by two different emergency medicine specialists. Measures were then taken for assessment of discriminatory power and calibration of the model. RESULTS: Data from 2905 patients were gathered (73.17% were male; the mean age was 33.53 ± 15.42 years). Area under the receiver operating characteristics curve of the TIRC model for detection of thoracic traumatic injuries was 0.93 (95%CI: 0.93-0.94). Sensitivity and specificity of the model were 100 (98.91-100) and 67.65 (65.76-69.45), respectively. The intercept of TIRC calibration plot was 0.08 (95%CI: 0.07-0.09), and its slope was 1.19 (95%CI: 1.15-1.24), which are indicative of the model being perfect in detecting presence or absence of lesions in chest radiograms. CONCLUSION: The findings are corroborative of external validation, good discrimination, and proper calibration of TIRC model in screening of multiple trauma patients for obtaining chest radiograms.

Nutrition and lung cancer: a case control study in Iran.

BACKGROUND: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. METHOD: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. RESULT: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). CONCLUSION: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran.