Machine learning-based classifiers to predict metastasis in colorectal cancer patients.

Background: The increasing prevalence of colorectal cancer (CRC) in Iran over the past three decades has made it a key public health burden. This study aimed to predict metastasis in CRC patients using machine learning (ML) approaches in terms of demographic and clinical factors. Methods: This study focuses on 1,127 CRC patients who underwent appropriate treatments at Taleghani Hospital, a tertiary care facility. The patients were divided into training and test datasets in an 80:20 ratio. Various ML methods, including Naive Bayes (NB), random rorest (RF), support vector machine (SVM), neural network (NN), decision tree (DT), and logistic regression (LR), were used for predicting metastasis in CRC patients. Model performance was evaluated using 5-fold cross-validation, reporting sensitivity, specificity, the area under the curve (AUC), and other indexes. Results: Among the 1,127 patients, 183 (16%) had experienced metastasis. In the predictionof metastasis, both the NN and RF algorithms had the highest AUC, while SVM ranked third in both the original and balanced datasets. The NN and RF algorithms achieved the highest AUC (100%), sensitivity (100% and 100%, respectively), and accuracy (99.2% and 99.3%, respectively) on the balanced dataset, followed by the SVM with an AUC of 98.8%, a sensitivity of 97.5%, and an accuracy of 97%. Moreover, lower false negative rate (FNR), false positive rate (FPR), and higher negative predictive value (NPV) can be confirmed by these two methods. The results also showed that all methods exhibited good performance in the test datasets, and the balanced dataset improved the performance of most ML methods. The most important variables for predicting metastasis were the tumor stage, the number of involved lymph nodes, and the treatment type. In a separate analysis of patients with tumor stages I-III, it was identified that tumor grade, tumor size, and tumor stage are the most important features. Conclusion: This study indicated that NN and RF were the best among ML-based approaches for predicting metastasis in CRC patients. Both the tumor stage and the number of involved lymph nodes were considered the most important features.

Evaluation of tumor-educated platelet long non-coding RNAs (lncRNAs) as potential diagnostic biomarkers for colorectal cancer.

INTRODUCTION: Cancer-derived circulating components are increasingly considered as candidate sources for non-invasive diagnostic biomarkers. This study aimed to investigate the expression of tumor-educated platelet (TEP) long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) patients and determine whether it could be served as a potential tool for CRC diagnosis. MATERIALS AND METHODS: Relative quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of three cancer-related platelet-derived lncRNAs CCAT1, HOTTIP, and XIST in 75 CRC patients and 42 healthy controls. Quantitative data were analyzed by SPSS (IBM Corp., Armonk, NY, USA) for comparison of cancer and non-cancer individuals. The receiver operating characteristic (ROC) curve analysis was further performed to assess the diagnostic values of lncRNAs within the CRC patients. RESULTS: The expression levels of lncRNAs colon cancer associated transcript 1 (CCAT1) (P = 0.006) and HOXA transcript at the distal tip (HOTTIP) (P = 0.049), but not X-inactive specific transcript (XIST) (P = 0.12), were significantly upregulated in CRC patients compared to healthy individuals. However, there were no significant correlations between platelet lncRNAs and clinicopathological characteristics, including sex, age, tumor location, differentiation, and size (all at P > 0.05). The area under the ROC curve (AUC) of the lncRNA CCAT1 was 0.61 (sensitivity, 71%; specificity, 50%). CONCLUSION: TEP lncRNA CCAT1 is detectable in the circulation of CRC patients and could be considered as a potential diagnostic biomarker.

Relationship between long non-coding RNAs and Hippo signaling pathway in gastrointestinal cancers; molecular mechanisms and clinical significance.

Long non-coding RNAs (lncRNAs) play a significant biological role in the regulation of various cellular processes such as cell proliferation, differentiation, apoptosis and migration. In various malignancies, lncRNAs interplay with some main cancer-associated signaling pathways, including the Hippo signaling pathway to regulate the various cellular processes. It has been revealed that the cross-talking between lncRNAs and Hippo signaling pathway involves in gastrointestinal (GI) cancers development and progression. Considering the clinical significance of these lncRNAs, they have also been introduced as potential biomarkers in diagnostic, prognostic and therapeutic strategies in GI cancers. Herein, we review the mechanisms of lncRNA-mediated regulation of Hippo signaling pathway and focus on the corresponding molecular mechanisms and clinical significance of these non-coding RNAs in GI cancers.

Role of the VEGF in virus-associated cancers.

The role of numerous risk factors, including consumption of alcohol, smoking, having diet high in fat and sugar and many other items, on caner progression cannot be denied. Viral diseases are one these factors, and they can initiate some signalling pathways causing cancer. For example, they can be effective on providing oxygen and nutrients by inducing VEGF expression. In this review article, we summarised the mechanisms of angiogenesis and VEGF expression in cancerous tissues which are infected with oncoviruses (Epstein-Barr virus, Human papillomavirus infection, Human T-lymphotropic virus, Kaposi's sarcoma-associated herpesvirus, Hepatitis B and hepatitis C virus).

Ginger (Zingiber Officinale Roscoe) ameliorates ethanol-induced cognitive impairment by modulating NMDA and GABA-A receptors in rat hippocampus.

Brain damage caused by ethanol abuse may lead to permanent damage, including severe dementia. The aim of this study was to investigate the effects of ginger powder on ethanol-induced cognitive disorders by examining oxidative damage and inflammation status, and the gene expression of N-methyl-D-aspartate (NMDA) and γ-Aminobutyric acid (GABA)-A receptors in the hippocampus of male rats. 24 adult male Sprague-Dawley rats were allocated randomly to four groups as follows control, ethanol (4g/kg/day, by gavage), ginger (1g/kg/day, by gavage), and ginger-ethanol. At the end of the study, memory and learning were evaluated by the shuttle box test. Moreover, to explore mechanisms involved in ethanol-induced cognitive impairment and the protective effect of ginger, the expression of Nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), NMDA receptor, and GABA-A receptor was measured along with inflammatory and oxidative biomarkers in the hippocampus tissue. The results showed that ethanol could induce cognitive impairment in the ethanol group, while pretreatment with ginger could reverse it. The gene expression of the NF-κB/ Tumor necrosis factor (TNF)-α/Interleukin (IL)-1ß pathway and NMDA and GABA-A receptors significantly increased in the ethanol group compared to the control group. While pretreatment with ginger could significantly improve ethanol-induced cognitive impairment through these pathways in the ginger-ethanol group compared to the ethanol group (P < 0.05). It can be concluded that ginger powder could ameliorate ethanol-induced cognitive impairment by modulating the expression of NMDA and GABA-A receptors and inhibiting oxidative damage and the NF-κB/TNF-α/IL-1ß pathway in the rat hippocampus.

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis / Incidência e resultados associados ao estado da menopausa em pacientes com COVID-19: Uma revisão sistemática e metanálise

Abstract Objective Menopause causes several changes in the body that may affect the response to COVID-19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. Methods Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. Results Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p= 0.003). Conclusion The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

Resumo Objetivo A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. Métodos Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. Resultados No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086-1,486; p = 0,003). Conclusão A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Menopause causes several changes in the body that may affect the response to COVID -19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. METHODS: Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. RESULTS: Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p = 0.003). CONCLUSION: The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

OBJETIVO: A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. MéTODOS: Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. RESULTADOS: No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086­1,486; p = 0,003). CONCLUSãO: A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach.

Background: Cancer stem cells (CSC), as responsible issues to cancer development and progression, play a crucial role in tumorigenesis, recurrence, metastasis, and chemoresistance. Both hyperthermia and photodynamic therapy (PDT) may be effective for cancer treatment, particularly when combined with other therapeutic approaches. This study aimed to evaluate the effect of hyperthermia combined with PDT on colorectal CSC and the gene expression of the CSC markers, presenting a more effective approach for cancer therapy. Methods: The study was conducted in the Pasteur institute of Iran, Tehran, Iran in 2018. We evaluated the anticancer role of hyperthermia, Gold nanoparticles coated with curcumin (Cur-GNPs) in PDT and combination of the two approaches on cell viability and the expression of CSC markers, Nanog and Oct4 in colorectal cancer cell line HT-29. The cytotoxicity effect of Cur-GNPs against the cells was assessed in vitro. The cell viability was assessed using MTT assay, and the expression analysis of the CSC genes was evaluated using a q-real-time PCR. Results: Cell viability was decreased by PDT (P=0.015) and the combination therapy (P=0.006) but not by hyperthermia alone (P=0.4), compared to control. Also, the expression of CSC markers, Nanog and Oct4 was shown to significantly down-regulate in all hyperthermia, PDT and combination groups. Conclusion: Hyperthermia combined with PDT was indicated to be more efficient in eliminating tumors than hyperthermia or PDT alone.

Association of serum vitamin D status with serum pro-inflammatory cytokine levels and clinical severity of fibromyalgia patients.

BACKGROUND & AIM: The role of vitamin D deficiency in fibromyalgia (FM) pathogenesis is not clearly understood. In this study, we evaluated the association of serum vitamin D status of FM patients with laboratory indices of inflammation, as well as clinical indices of FM. MATERIALS & METHODS: Ninety-two female FM patients with a mean age of 42.4 ± 7.4 years were included in this cross-sectional study. Serum vitamin D, serum IL-6, and serum IL-8 levels were evaluated using an enzyme-linked immunosorbent assay. Serum vitamin D levels were categorized as deficient (<20 ng/ml), insufficient (20-30 ng/ml), and sufficient (30-100 ng/ml). The clinical severity of the disease was assessed by the fibromyalgia impact questionnaire (FIQ) and widespread pain index (WPI). RESULTS: The mean serum IL-6 level was significantly higher in vitamin D-deficient patients in comparison with vitamin D-sufficient patients (P = 0.039). The mean serum IL-8 level was also significantly higher in vitamin D-deficient patients in comparison with vitamin D-sufficient patients (P < 0.001). A significant positive correlation was found between the serum IL-8 level and FIQ scores (r = 0.389, p = 0.001) and the WPI of the patients (0.401, p < 0.001). Serum IL-6 level was significantly correlated with the WPI of the patients (r = 0.295, p = 0.004), but not with FIQ scores (r = 0.134, p = 0.066). Serum vitamin D status was not associated with either FIQ scores or WPI. CONCLUSION: In FM patients, serum vitamin D deficiency is associated with higher levels of serum pro-inflammatory cytokines, and higher levels of serum pro-inflammatory cytokines are associated with greater FM impact.

How durable are the effects of cognitive-behavioural therapy in controlling fibromyalgia symptoms? A prospective cohort study.

PURPOSE: Cognitive-behavioural therapy (CBT) is widely used for the treatment of fibromyalgia. However, there is no consensus on the durability of its effects on these patients. In this study, we evaluated how durable are the effects of CBT in controlling fibromyalgia symptoms. METHODS: Forty-eight fibromyalgia patients treated with traditional face-to-face CBT were included. CBT was performed in 20 consecutive group sessions. To evaluate the durability of treatment, the effects of CBT on fibromyalgia symptoms were checked at five time-points: before the CBT, immediately after the CBT, 3 months after the CBT, 6 months after the CBT, and 12 months after the CBT. Outcome measures were the Fibromyalgia impact questionnaire (FIQ) and widespread pain index (WPI). RESULTS: The mean FIQ score of the patients was 68.3 ± 18.8 before the CBT and 50.5 ± 14.1 1 week after the CBT (p < 0.001). The mean post-CBT FIQ score did not significantly change three and 6 months after the CBT (p = 0.11 and p = 0.09, respectively) while the positive effects of CBT significantly diminished after 12 months (p < 0.001). The mean WPI was 10.4 ± 3.6 before the CBT and 8.6 ± 3.1 1 week after the end of CBT (p < 0.001). The mean WPI of three and 6 months was not statistically different from that immediately after the CBT (p = 0.18 and p = 0.15, respectively), while after 12 months, it significantly worsened (p < 0.001). CONCLUSION: CBT's beneficial effects for fibromyalgia patients are durable for 6 months. Complementary CBT sessions could be implemented to boost the CBT effect after this period.

Predicting metastasis in gastric cancer patients: machine learning-based approaches.

Gastric cancer (GC), with a 5-year survival rate of less than 40%, is known as the fourth principal reason of cancer-related mortality over the world. This study aims to develop predictive models using different machine learning (ML) classifiers based on both demographic and clinical variables to predict metastasis status of patients with GC. The data applied in this study including 733 of GC patients, divided into a train and test groups at a ratio of 8:2, diagnosed at Taleghani tertiary hospital. In order to predict metastasis in GC, ML-based algorithms, including Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (RT) and Logistic Regression (LR), with 5-fold cross validation were performed. To assess the model performance, F1 score, precision, sensitivity, specificity, area under the curve (AUC) of receiver operating characteristic (ROC) curve and precision-recall AUC (PR-AUC) were obtained. 262 (36%) experienced metastasis among 733 patients with GC. Although all models have optimal performance, the indices of SVM model seems to be more appropiate (training set: AUC: 0.94, Sensitivity: 0.94; testing set: AUC: 0.85, Sensitivity: 0.92). Then, NN has the higher AUC among ML approaches (training set: AUC: 0.98; testing set: AUC: 0.86). The RF of ML-based models, which determine size of tumor and age as two essential variables, is considered as the third efficient model, because of higher specificity and AUC (84% and 87%). Based on the demographic and clinical characteristics, ML approaches can predict the metastasis status in GC patients. According to AUC, sensitivity and specificity in both SVM and NN can be regarded as better algorithms among 6 applied ML-based methods.

Intra-articular remifentanil on postoperative pain in knee arthroscopic surgery; a double blind randomized clinical trial.

BACKGROUND: We aimed to assess the efficacy of intra-articular remifentanil in relieving postoperative pain after knee arthroscopy. METHODS: We conducted a double-blind randomized clinical trial study on 60 patients. Patients were divided into two equal groups. The control group received 25 ml of intra-articular normal saline, and the intervention group received 200 µg of remifentanil dissolved in 25 ml of saline. We evaluated at rest postoperative pain at 1, 3, 6, 12, 18, and 24 h after the surgery using the Visual Analog Scale (VAS). Patients with VAS scores of 4 or more received meperidine (pethidine). The first time meperidine was requested and the total amount of meperidine consumed was recorded. RESULTS: Out of 60 patients, 49 were male (81.6%), and the mean age of participants was 32.71 (7.02) years. An hour after the surgery, the control group showed a mean VAS score of 8.66 (1.26), and decreased to 2.53 (1.67) at the end of 24 h. The intervention group started with a mean VAS score of 2.23 (1.81) and ended at 0.10 (0.305). All patients in the control group and 11 (36.7%) patients in the intervention group asked for analgesics during follow-up. The mean total meperidine dose in the control and intervention groups was 108.33 (23.97) mg and 13.33 (19.40) mg, respectively (P < 0.001; 95% confidence interval of the difference 83.72 to 106.27). CONCLUSIONS: Intra-articular remifentanil may decrease postoperative pain and analgesic requirements in patients undergoing knee arthroscopy.

Simple mucopexy and hemorrhoidal arterial ligation with and without Doppler guide: a randomized clinical trial for short-term outcome.

PURPOSE: Hemorrhoids are the most common benign anorectal diseases. Mucopexy strengthens the anal canal mucosa, which can be performed alone or in combination with Doppler-guided hemorrhoidal artery ligation (DG-HAL). In this study, we compared the postoperative complications between simple mucopexy plus HAL with and without a Doppler guide. METHODS: This study was performed as a single-blinded randomized clinical trial. Patients referred to a tertiary colorectal referral clinic with grades 3 and 4 hemorrhoids who were candidates for surgical intervention entered the study. Thirty-six patients were randomly divided into 2 groups. Group A including 18 patients underwent mucopexy and DG-HAL and the other 18 patients (group B) underwent standard mucopexy and HAL without a Doppler guide. Postoperative pain score and the duration of oral analgesic consumption were recorded. Additionally, postoperative symptoms and complications were recorded and compared between the 2 methods. RESULTS: There was no significant difference between the 2 groups in terms of pain score and the duration of postoperative analgesic consumption as well as the incidence of postoperative complications. Besides, the primary grade of hemorrhoids was not significantly associated with recurrence, but there was a significant association between body mass index and Wexner score (WS) with recurrence. The mean WS of patients showed a significant decrease in both groups postoperatively. However, the rate of WS reduction was not remarkably different between the 2 groups. CONCLUSION: Simple mucopexy with blind HAL (without Doppler guide) might be considered for the treatment of grades 3 and 4 hemorrhoids effectively.

Regulation of long non-coding RNAs XIST and ROR induced by homeodomain protein TGIF2LX in colorectal cancer.

Background: Homeodomain protein transforming growth factor beta-induced factor 2 like, X-linked (TGIF2 LX) has been demonstrated to act as a transcription factor and regulate cancer cell proliferation. Long non-coding RNAs (lncRNAs) are well known as molecular regulators of colorectal cancer (CRC). Our aim was to evaluate the clinical and biological significance of TGIF2 LX and its effect on lncRNAs regulator of reprogramming (ROR) and X-inactive specific transcript (XIST) expression in CRC cells. Materials and Methods: Thirty-six CRC tissues and 22 adjacent normal colorectal tissues were subjected to RNA extraction and analysis of TGIF2 LX gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). The human SW1116 cell line was transfected with cDNA for the TGIF2 LX gene. Microscopic analysis, reverse transcriptase PCR, and western blotting were used for confirming at transcriptional and translational levels. Methyl thiazolyl tetrazolium and colony formation assays were applied for evaluating the in vitro cell viability and colony-forming ability, respectively. LncRNA expression analysis was carried out using qRT-PCR. Results: The results showed that the expression levels of TGIF2 LX were significantly downregulated in CRC tissues compared to adjacent normal tissues (P = 0.032). Furthermore, the overexpression of TGIF2 LX could reduce the CRC cell line proliferation. The gene expression analysis revealed a significantly reduced level of lncRNA ROR and lncRNA XIST in TGIF2 LX-transfected SW1116 cells compared to nontransfected cells. Conclusion: Our findings provided evidence of molecular mechanisms by which TGIF2 LX may interact with lncRNAs ROR and XSIST to regulate CRC development by acting as a tumor suppressor. Thus, this protein may potentially be a promising option for CRC gene-based therapeutic strategies.

Epigenetic regulation of gastrointestinal cancers mediated by long non-coding RNAs.

Long noncoding RNAs (lncRNAs), as well-known modulator of the epigenetic processes, have been shown to contribute to normal cellular physiological and pathological conditions such as cancer. Through the interaction with epigenetic regulators, an aberrant regulation of gene expression can be resulted due to their dysregulation, which in turn, can be involved in tumorigenesis. In the present study, we reviewed the lncRNAs' function and mechanisms that contributed to aberrant epigenetic regulation, which is directly related to gastrointestinal cancer (GI) development and progression. Findings indicated that epigenetic alterations may involve in tumorigenesis and are valuable biomarkers in case of diagnosing, assessing of risk factors, and predicting of GI cancers. This review summarized the accumulated evidence for biological and clinical application to use lncRNAs in GI cancers, including colorectal, gastric, oral, liver, pancreatic and oesophageal cancer.

The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.

The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.

Green tea could improve elderly hypertension by modulating arterial stiffness, the activity of the renin/angiotensin/aldosterone axis, and the sodium-potassium pumps in old male rats.

Hypertension is a major health problem common in the elderly people. Green tea is a popular beverage recommended in folk medicine for lowering blood pressure. However, the molecular mechanisms involved in the antihypertensive effects of green tea are not fully understood. Therefore, the aim of this study was to investigate the antihypertensive effects of green tea on high-salt diet-induced hypertension in old male rats. Forty old male rats were divided into five groups: control, hypertensive, and hypertensive-green tea (2, 4, and 6 g/kg). Heart rate (HR) and systolic blood pressure (SBP) were measured. Cardiac and renal histology were also performed. Lipid profile, NO, angiotensin II (Ang II), and aldosterone were determined, and the expression of eNOS, ATIR and ATIIR, aldosterone receptor, and Atp1a1 were measured. Green tea could significantly decrease HR and SBP, lipid profiles, renin-angiotensin II-aldosterone system activity, and Ang II signaling in kidney tissue of hypertensive rats (p < .01). It also increased Atp1a1, Nrf2, and eNOS expression along with antioxidant enzymes activity and NO concentration (p < .05) and decreased NF-ĸB and iNOS expression and IL-1ß levels in the heart, kidneys, and aorta of rats with hypertension. It can be concluded that green tea can improve salt-induced blood pressure by modulating the function of the renin-angiotensin-aldosterone system, enhancing the synthesis of nitric oxide in the endothelium, increasing antioxidant activity and suppressing inflammation in the heart and kidney, improving the expression of the sodium-potassium pump, and reduction in serum lipids and glucose in aged male rats. PRACTICAL APPLICATIONS: The results of this study showed that green tea could improve hypertension in elderly rats by modulating (1) the expression of the sodium-potassium pump in the heart, kidney, and aortic tissues, (2) the activity of the renin-angiotensin II-aldosterone system in kidney, (3) enhancing antioxidant and anti-inflammatory activities in the heart, aorta, and kidneys, (4) enhancing the synthesis of nitric oxide in the endothelium, and (5) lowering lipid profile. The results of these studies show that the consumption of green tea and its products can be a good candidate for the prevention of cardiovascular diseases such as hypertension in the elderly. In addition, attention to its bioactive compounds can be considered by researchers as an independent therapeutic strategy or adjunctive therapy for the treatment of hypertension.

Plasma miR-183-5p in colorectal cancer patients as potential predictive lymph node metastasis marker.

Background: Lymph node metastasis (LNM) is a point that often, treatment is not effective in colorectal cancer (CRC). Clinical and pathologic markers of prognosis help clinicians in selecting patients for adjuvant therapy after surgical resection in CRC. MiR-183-5p has been demonstrated to play as an oncogene in CRC, although its biological role still remains unclear. The aim of this study was to evaluate the expression of miR-183-5p in CRC and its potential relevance to clinicopathological characteristics as a prognostic biomarker. Materials and Methods: In this case-control study, 33 CRC plasma samples at stage I-II-III, as well as plasma samples from 13 healthy controls, were collected. The relative expression levels of miR-183-5p in cancer and the normal samples were measured by quantitative real-time PCR. We analyzed their correlation with clinicopathological parameters and prognostic value. Results: Our results indicated that miR-183-5p was significantly overexpressed in CRC samples compared to healthy controls (P < 0.001) from a cutoff value of 3.9 with a sensitivity of 89% and a specificity of 91% and an AUC value of 0.74. Further analysis showed that a high plasma expression level of miR-183-5p was significantly associated with LNM and higher tumor/node/metastases stage (III) (P-value < 0.001).In conclusion, the overexpression of miR-183-5p is highly related to advanced clinical stage, LNM and poor prognosis of CRC, indicating that miR-183-5p may serve as a predictive biomarker for the prognosis or the aggressiveness of CRC.

Neoantigens and their clinical applications in human gastrointestinal cancers.

BACKGROUND: Tumor-specific neoantigens are ideal targets for cancer immunotherapy. As research findings have proved, neoantigen-specific T cell activity is immunotherapy's most important determinant. MAIN TEXT: There is sufficient evidence showing the role of neoantigens in clinically successful immunotherapy, providing a justification for targeting. Because of the significance of the pre-existing anti-tumor immune response for the immune checkpoint inhibitor, it is believed that personalized neoantigen-based therapy may be an imperative approach for cancer therapy. Thus, intensive attention is given to strategies targeting neoantigens for the significant impact with other immunotherapies, such as the immune checkpoint inhibitor. Today, several algorithms are designed and optimized based on Next-Generation Sequencing and public databases, including dbPepNeo, TANTIGEN 2.0, Cancer Antigenic Peptide Database, NEPdb, and CEDAR databases for predicting neoantigens in silico that stimulates the development of T cell therapies, cancer vaccine, and other ongoing immunotherapy approaches. CONCLUSIONS: In this review, we deliberated the current developments in understanding and recognition of the immunogenicity of newly found gastrointestinal neoantigens as well as their functions in immunotherapies and cancer detection. We also described how neoantigens are being developed and how they might be used in the treatment of GI malignancies.