The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis.

Non-coding RNAs (ncRNAs) are emerging as important regulators in various pathological conditions, including human cancers. NcRNAs exert potentially crucial effects on cell cycle progression, proliferation, and invasion in cancer cells by targeting various cell cycle-related proteins at transcriptional and post-transcriptional levels. As one of the key cell cycle regulatory proteins, p21 is involved in various processes, including the cellular response to DNA damage, cell growth, invasion, metastasis, apoptosis, and senescence. P21 has been shown to have either a tumor-suppressive or oncogenic effect depending on the cellular localization and posttranslational modifications. P21 exerts a significant regulatory effect on both G1/S and G2/M checkpoints by regulating the function of cyclin-dependent kinase enzymes (CDKs) or interacting with proliferating cell nuclear antigen (PCNA). P21 has an important effect on the cellular response to DNA damage by separating DNA replication enzymes from PCNA and inhibiting DNA synthesis resulting in G1 phase arrest. Furthermore, p21 has been shown to negatively regulate the G2/M checkpoint through the inactivation of cyclin-CDK complexes. In response to any cell damage caused by genotoxic agents, p21 exerts its regulatory effects by nuclear preservation of cyclin B1-CDK1 and preventing their activation. Notably, several ncRNAs, including lncRNAs and miRNAs, have been shown to be involved in tumor initiation and progression through the regulation of the p21 signaling axis. In this review, we discuss the miRNA/lncRNA-dependent mechanisms that regulate p21 and their effects on gastrointestinal tumorigenesis. A better understanding of the regulatory effects of ncRNAs on the p21 signaling may help to discover novel therapeutic targets in gastrointestinal cancer.

Iron nanoparticles as novel vaccine adjuvants.

The poor immunogenicity of peptide vaccines compared to conventional ones re usually improved by applying different adjuvants. As chemical or biological substances, adjuvants are added to vaccines to enhance and prolong the immune response. According to considerable investigations over the recent years in the context of finding new adjuvants, a handful of vaccine adjuvants have been licensed for human use. Recently, engineered nanoparticles (NPs) have been introduced as novel alternatives to traditional vaccine adjuvant. Metallic nanoparticles (MeNPs) are among the most promising NPs used for vaccine adjuvant as well as the delivery system that can improve immune responses against pathogens. Iron NPs, as an important class of MeNPs, have gained increasing attention as novel vaccine adjuvants. These particles have shown acceptable results in preclinical studies. Hence, understanding the physicochemical properties of iron NPs, including size, surface properties, charge and route of administration, is of substantial importance. The aim of this review is to provide an overview of the immunomodulatory effects of iron NPs as novel adjuvants. Furthermore, physicochemical properties of these NPs were also discussed.

Investigations of antiproliferative and antioxidant activity of ß-lactam morpholino-1,3,5-triazine hybrids.

This article reports for the first time the synthesis of some novel ß-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a-c, 9a-c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-ß-lactams 8a-l, 10a-f and 12a-c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC50 = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and ß-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.

Three-component synthesis of chromeno ß-lactam hybrids for inflammation and cancer screening.

Highly diastereoselective synthesis of chromeno ß-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired ß-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H-H COSY and H-C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. ß-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. ß-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

Surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy.

BACKGROUND AND OBJECTIVE: Colorectal cancer is one of the main causes of mortality in both developed and developing countries, including Iran. One of the treatments available for colorectal cancer is chemotherapy, of which nausea and emesis are the side effects. Owing to problems in controlling the side effects, a combination of medicine and non-medicine interventions is usually used. Self-care is one of the non-medicine interventions in this regard. The present study was aimed at surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy. METHODS: A semi-experimental study was carried out in Imam Reza Hospital of Kermanshah, Iran. The sample group comprised 52 patients with colorectal cancer under chemotherapy. Data gathering tools included a demographics questionnaire and Morrow Assessment of Nausea and Emesis. To control intensity of nausea and emesis, a package of self-care measures including muscular progressive relaxation, music, and education on nutrition was used. Afterward, the collected data were analyzed using statistical tests such as Shapiro-Wilk test (to check normal distribution of the data), Mann-Whitney U test, Wilcoxon test, and chi-square test with the help of SPSS 20. RESULTS: The results showed a considerable decrease in intensity and frequency of nausea and emesis after the intervention. The p-value of Mann-Whitney U test results with regard to intensity of nausea in the experiment and control groups after the intervention was 0.029; this figure for intensity of emesis was 0.009, which indicated effectiveness of the self-care program. CONCLUSION: As the results showed, using self-care program could be effective in attenuating intensity of emesis and nausea in colorectal cancer patients under chemotherapy. So, it can be concluded that the use of this program can increase the patient's self-care ability to control vomiting and nausea, which can be considered as a complementary approach to the antiemetic medications.