Inhibition of microRNA-21 via locked nucleic acid-anti-miR suppressed metastatic features of colorectal cancer cells through modulation of programmed cell death 4.

Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid-modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression

Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis

Leucine-rich G protein-coupled receptor 5 (LGR5) is a marker of cancer stem cells (CSCs) in various cancers.Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigatecorrelation between LGR5 expression and outcomes of cancer patients under study through a systematic review andmeta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopusdatabases until December 21, 2022. This study was conducted to examine correlation between LGR5 expression anddifferent clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS),and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95%confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis wasconducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly,high-level expression of LGR5 was related to poor prognosis in terms of OS, higher tumor stage, presence of distantmetastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors,including the study area, evaluation method, and type of cancer, can influence the correlation between LGR5 expressionand negative prognosis in cancer patients. According to the results of our study, LGR5 overexpression was related topoor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patientswith high LGR5 expression. In conclusion, LGR5 may serve as a potential prognostic marker for predicting survival incertain cancer types

The frequencies of peripheral blood CD5⁺CD19⁺ B cells, CD3⁻CD16⁺CD56⁺ NK, and CD3⁺CD56⁺ NKT cells and serum interleukin-10 in patients with multiple sclerosis and neuromyelitis optica spectrum disorder

Background: Multiple sclerosis (MS) and neuromyelitis optica syndrome disease (NMOSD) are inflammatory diseases of the central nervous system. The pathogenesis and treatments for these two conditions are very different. Natural killer (NK) and natural killer T (NKT) cells are immune cells with an important role in shaping the immune response. B cells are involved in antigen presentation as well as antibody and cytokine production. There is conflicting evidence of the roles of NK, NKT, and B cells in the two conditions. We aimed to compare the frequency of CD3−CD16+CD56+NK, CD3+ CD56+ NKT, and CD5+CD19+ B cells in the peripheral blood and serum Interleukin-10 (IL-10) in patients with MS and NMOSD. Methods: CD19+CD5+ B, CD3− CD16+CD56+ NK, and CD3+CD56+ NKT cells were quantitated by flow cytometry in 15 individuals with Interferon-Beta (IFN-β) treated relapsing–remitting MS (RRMS), 15 untreated RRMS, and 15 NMOSD patients as well as 30 healthy controls (HC). Serum IL-10 was measured using an enzyme-linked immunosorbent assay (ELISA). Results: The percentage of CD3−CD56+CD16+ NK cells in the peripheral blood of IFN-treated MS (1.81 ± 0.87) was significantly lower than for untreated RRMS (4.74 ± 1.80), NMOSD (4.64 ± 1.26) and HC (5.83 ± 2.19) (p < 0.0001). There were also differences for the percentage of CD3−CD16+ and CD3−CD56+ cells (p < 0.001 and p < 0.0007; respectively). IFN-treated RRMS (2.89 ± 1.51) had the lowest proportion of CD3+CD56+ among the study groups (p < 0.002). Untreated RRMS (5.56 ± 3.04) and NMOSD (5.47 ± 1.24) had higher levels of CD3+CD56+ than the HC (3.16 ± 1.98). The mean percentage of CD19+CD5+ B cells in the peripheral blood of untreated RRMS patients (1.32 ± 0.67) was higher compared to the patients with NMOSD (0.30 ± 0.20), HC (0.5 ± 0.22) and IFN-treated RRMS (0.81 ± 0.17) (p < 0.0001). Serum interleukin-10 was significantly higher in the IFN-treated RRMS (8.06 ± 5.39) and in HC (8.38 ± 2.84) compared to untreated RRMS (5.07 ± 1.44) and the patients with NMOSD (5.33 ± 2.56) (p < 0.003). Conclusions: The lower proportion of CD3−CD56+ CD16+ NK and CD3+CD56+ cells in peripheral blood of IFN-treated RRMS compared to other groups suggests the importance of immunomodulation in patients with RRMS disorder. Based on the differences in CD19+CD5+ B cells and serum IL-10 between patients and HC, supplementary assessments could be of value in clarifying their roles in autoimmunity

The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review

Colorectal cancer (CRC) is the third most common cause of cancer globally and the fourth attributable cause of mortality and morbidity due to cancer. An emerging factor contributing to CRC is the gut microbiota and the cellular changes associated with it. Further insights on this may help in the prevention, diagnosis and new therapeutic approaches to colorectal cancer. In most cases of CRC, genetic factors appear to contribute less to its aetiology than environmental and epigenetic factors; therefore, it may be important to investigate these environmental factors, their effects, and the mechanisms that may contribute to this cancer. The gut microbiota has recently been highlighted as a potential risk factor that may affect the structural components of the tumor microenvironment, as well as free radical and enzymatic metabolites directly, or indirectly. Many studies have reported changes in the gut microbiota of patients with colorectal cancer. What is controversial is whether the cancer is the cause or consequence of the change in the microbiota. There is strong evidence supporting both possibilities. The presence of Fusobacterium nucleatum in human colorectal specimens has been demonstrated by RNA-sequencing. F. nucleatum has been shown to express high levels of virulence factors such as FadA, Fap2 and MORN2 proteins. Our review of the published data suggest that F. nucleatum may be a prognostic biomarker of CRC risk, and hence raises the potential of antibiotic treatment of F. nucleatum for the prevention of CRC

Evaluation of the Thermal Processes on Changing the Phenotypic Characteristics of Escherichia coli Strains from Ice Cream Compared to Non-Pasteurized Milk

Escherichia coli (E. coli) is shocked by various temperature processes in milk, which forces the organism to make proteins as a result of changes in the synthesis of enzymes that might give the strain special characteristics. The purpose of this study was to investigate the effects of the heat shock factor on changing the results of biochemical and molecular tests among E. coli strains obtained from ice cream and non-pasteurized milk when compared to a reference strain from the American-type culture collection (ATCC) in order to determine the phenotypic variation caused by the temperature conditions of the manufacturing process. Furthermore, isolates with characteristics similar to E. coli were discovered, but they were not E. coli and caused some ambiguity. To test the E. coli contamination of traditional and industrial ice cream, 82 samples were chosen at random. SDS-PAGE and 16S rDNA sequencing were carried out, as well as phenotypic testing. Isolated strains did not exactly match the reference strain. The results of biochemical testing and protein analysis revealed that the isolates were diverse. Samples E. coli phenons were classified. In the electrophoresis, the ice cream strain had two protein bands in the 20.75 and 23.59 kDa ranges that were distinct from the reference strain. These isolates appear to experience alterations in enzyme characteristics and structural proteins as a result of being exposed to various temperature conditions, such as pasteurization and frigidity. When compared to the reference strain, the calculated similarity percentage of the elicited isolate varied from 60 to 70%. The electrophoretic patterns of E. coli isolated elicited from milk samples differed from E. coli isolated obtained from the ice cream. The distinctions were in the intensity or position of the bands. The results also revealed that when isolates are subjected to thermal stresses, they exhibit a pattern similar to that of ice cream isolates. These considerations are made because a change in protein composition might result in a change in biochemical features, resulting in uncertainty in its identification. Sequences revealed that the sequences were related to E. coli 16S rDNA, despite differences in phenotypic and electrophoretic features between the isolated bacteria and the reference strain E. coli ATCC 25922. Our findings revealed that 16S rDNA could potentially be used to instantly implement an appropriate preventive measure for the purpose of identifying this type of bacteria and avoid some ambiguity

Novel delivery system for natural products: Nano-curcumin formulations

Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions

Evaluation of the Escherichia coli (E.coli) Strains based on protein profiles obtained from traditional Ice cream in Isfahan City

Introduction: Bacterial strains present in food products undergo different thermal processes such as coldness and warmth. Such cases cause a shock in bacteria and force the bacteria to produce proteins and partly, develop a change in the production of enzyme. This can give the strain a special characteristic, knowledge of this characteristic will contribute to a timely and more precise identification. Materials and methods: During this time more than 100 samples have been examined, out of which, 48 Indol positive isolation samples were examined by phenotypic tests and sodium dodecyle sulphate polyacrylamide gel electrophoresis (SDS- PAGE). Results: &ndash; The results of numerical analysis of phenotypic characteristics and protein patterns showed that only 79% of the collected isolates (phenon 1 and 2) could be identified as E.coli compared with reference strains. E.coli strains from ice creams were showed some Variation in banding patterns. Major differences were observed in protein bands between 23.59 - and 20.79 -kDa molecular mass range which the isolates were compared with reference strains. Discussion and conclusion: Our study concluded that food&rsquo;s bacterial strains are influenced by temperatures in different processes and also it could stimulate the production of proteins or change the enzymes. Therefore, The reason of taking care of the issues is that changes in the proteins&rsquo; structures can lead to change in the biochemical properties, and finally this change can misguide us. Further research is being performed to characterize these atypical strains by molecular methods

Status of integrin subunit alpha 4 promoter DNA methylation in colorectal cancer and other malignant tumors: a systematic review and meta-analysis

Background and purpose: Although many recent studies have analyzed the validation of integrin subunit alpha 4 (ITGA4) biomarker for cancer detection in patients with various malignancies, the diagnostic value of ITGA4 methylation for malignant tumors remains uncertain. We performed a systematic review and meta-analysis to unravel the relationship between ITGA4 promoter methylation status and malignant tumors. Experimental approach: A meta-analysis was performed using the metaphor package in R 3.5 and Meta-Disc 1.4 software. Data were derived from a search of main electronic databases up to January 2022. SROC analysis was used to evaluate the status of ITGA4 promoter methylation in colorectal cancer (CRC) and other cancers. A total of 1232 tumor samples and 649 non-tumor samples from 13 studies were analyzed. Findings/Results: The pooled results including all types of cancer provided evidence that ITGA4 hypermethylation was more frequent in tumor samples than non-tumor samples (OR 13.32, 95% CI 7.96-22.29). Methylation of ITGA4 has a pooled sensitivity of 0.95 (95% CI: 0.94-0.97), a pooled specificity of 0.57 (95% CI: 0.54-0.60), and an area under the curve (AUC) of 0.94. When the analysis was performed independently for CRC, it revealed a higher association (OR = 20.77, 95% CI: 9.15-47.15). The assessment of ITGA4 methylation of tissue samples resulted in a pooled sensitivity of 0.99 (95% CI: 0.97-1.00) and a pooled specificity of 0.90 (95% CI: 0.86-0.93), and AUC of 0.94 for the diagnosis of CRC. Conclusion and implications: ITGA4 methylation analysis is a reliable method for CRC screening in tissue samples