miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.

In the regulation of gene expression, epigenetic factors like non-coding RNAs (ncRNAs) play an equal role in genetics. The role of microRNAs (miRNAs), which are members of the ncRNA family, in post-transcriptional gene regulation is well-documented and has important implications for both normal and abnormal biological processes, such as angiogenesis, proliferation, survival, and apoptosis. The purpose of this study was to synthesize previous research on miR-449a by analyzing published results from various databases, as there have been a number of investigations on miR-449's potential involvement in the development of human disorders. Based on our findings, miR-449 is strongly dysregulated in a wide range of diseases, from various cancers to cardiovascular diseases, cognitive impairments, and respiratory diseases, and it may play a pivotal role in the development of these problems. In addition, miR-449a functions as a crucial regulator of the expression of several well-known genes, including E2F-3, BCL2, NOTCH1, and SOX4. This, in turn, modulates various pathways and processes related to cancer, including Notch, PI3K, and TGF-ß, and contributes to the improvement of cancer drug sensitivity. Curiously, abnormalities in the expression of this miRNA may serve as diagnostic or prognostic indicators for distinguishing between healthy people and patients or to evaluate the survival rates for specific disorders. This article provides a synopsis of the current understanding of miR-449a's role in human disease development through its regulation of gene expression and the biological processes related to these genes and their linked processes. In addition, we have covered the topic of miR-449a's potential as a clinical feature (diagnosis and prognosis) indicator for a range of disorders, both neoplastic and non-neoplastic. In general, our goal was to gain a thorough comprehension of the numerous functions of miR-449a in different disorders.

The MicroRNAs (miRNAs) Expression in Benign Urological Diseases: A Systematic Review.

PURPOSE: The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing and analyzing the data linking microRNAs (miRNAs) expression in the pathophysiology of benign urological conditions, including overactive bladder (OAB), bladder outlet obstruction (BOO), bladder pain syndrome/interstitial cystitis (BPS/IC), and Lower urinary tract dysfunction (LUTD) is the objective of the current systematic review. MATERIALS AND METHODS: Evidence including all case-control, cohort, and cross-sectional studies that measure participants' MicroRNA as a biomarker for benign urological diseases has been gathered On January 2024, through searching MEDLINE via PubMed, Scopus, Web of Science, Embase, and ProQuest databases. Studies considered eligible that present information on the reference Gene, profile type, and serum levels of microRNA from patients diagnosed with benign urological disease including benign prostate hyperplasia (BPH) or benign prostate enlargement (BPE), overactive bladder (OAB), and bladder outlet obstruction (BOO). These studies appraised by the quality assessment checklist of Joanna Briggs Institute (JBI). RESULTS: A total of 4,587 records related to miRNAs in urological diseases were retrieved. Of these, we identified 28 records for our systematic study. The most frequently associated miRNA was 92a-3p identified which was found upregulated in OAB diagnosis. In BOO, miR-146a-5p was identified to be upregulated. miR-146a-5p was upregulated in BO, and for other benign conditions, different miRNAs were reported. 491-5p miRNAs were found deregulated in OAB-related studies. We expected other miRNAs to have the same trend in the OAB studies. InSUI miR-93 was the most frequent downregulated miRNA. The other reported miRNAs had similar frequencies. CONCLUSION: When it comes to the early detection and treatment of benign urological conditions, 92a-3p, miR-21, miR-199a-5p, and miR-146a-5p, and 491-5p have the potential to be employed as both a biomarker and a therapeutic target. The creation of pre-RNA or anti-RNA molecules within carrier vehicles that may be safely administered to patients should be made possible by technological advancements.

Anti-neoplastic effects of aprotinin on human breast cancer cell lines: In vitro study.

BACKGROUND: Aprotinin is a nonspecific serine protease inhibitor, which can inhibit plasminogen-plasmin system and matrix metalloproteinases. Aprotinin has been investigated as an antitumor agent. However, its antineoplastic effects on breast cancer (BC) have not been investigated yet. OBJECTIVES: The objective of this study was to assess the inhibitory effects of aprotinin on human BC cell lines. We assessed the effects of aprotinin on local invasion and survival of human BC cell lines MDA-MB-231, SK-BR-3 and MCF-7 in vitro. MATERIAL AND METHODS: CHEMICON cell invasion assay kit was used to assess local invasion, and (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay was used to determine the antiproliferative activity of aprotinin. Human dermal fibroblast (HDF-1) cell line was used as control normal cells. RESULTS: Cancer cell lines showed more invasion characteristics compared to HDF-1. Aprotinin significantly decreased the invasiveness of MDA-MB-231 in concentrations of 1 trypsin inhibitor unit (TIU)/mL, 1.3 TIU/mL and 1.7 TIU/mL in comparison with the untreated group (analysis of variance (ANOVA) p < 0.001). Treatment of SK-BR-3 with 1.3 TIU/mL aprotinin caused no significant reduction in invasiveness (p = 0.06). Treatment with different concentrations of aprotinin significantly decreased the surviving fraction and inhibited the growth of all cell lines tested in this study (analysis of variance (ANOVA) p < 0.001). Compared to cancer cell lines, normal HDF-1 cell line showed less sensitivity to antiproliferative effects of aprotinin, both in low and high doses. CONCLUSIONS: Aprotinin significantly inhibited the growth of human breast cancer cell lines MDA-MB-231, SK-BR-3 and MCF-7, and normal fibroblast cell line HDF-1. The growth inhibitory effect was more dominant in cancer cell lines. Inhibition of local invasion by aprotinin was significant only in the case of MDA-MB-231. Future molecular studies could shed further lights on mechanisms underlying antineoplastic effects of aprotinin and its potential therapeutic effects.

AGS cell line xenograft tumor as a suitable gastric adenocarcinoma model: growth kinetic characterization and immunohistochemistry analysis.

OBJECTIVES: Gastric cancer is the third leading cause of cancer-related death worldwide. The overall survival rate of patients is poor because gastric cancers are usually diagnosed at the late stages. Therefore, further research is needed and appropriate research tools are required to develop novel therapeutic approaches. MATERIALS AND METHODS: Eight female athymic nude mice with a C57BL/6 background were used in this study. AGS cells were inoculated into the flank. The tumor volumes were calculated and growth curves were drawn. When the volume of the tumors reached 1000 mm3, the animals were humanely euthanized with CO2 gas. After harvesting, tumors were analyzed with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC). A pathologist confirmed tumor entity through H&E staining. Tumors were evaluated for expression of HER-2, P53, Ki-67, CD34, cytokeratin 8 (CK8), vimentin, estrogen receptor (ER), and progesterone receptor (PR) utilizing immunohistochemistry. RESULTS: The tumor take rate was 62.5%, mean doubling time was 40.984 d, and the latency period was 30.62 days. The H&E staining results showed highly malignant hyperchromatin epithelial cells. IHC assessment showed the mutation status of P53 gene. The expression score of the CK8 protein in the tumor cells was +3. Vimentin protein was not expressed and changes in mesenchymal phenotype were not observed. Ki-67 IHC indicated that the proliferation rate was >43% and angiogenesis was defined as high MVD. CONCLUSION: The respective AGS xenograft model provides an opportunity to understand the pattern of tumor growth as well as to evaluate new gastric cancer therapies in in vivo studies.

Long­term behavioral, histological, biochemical and hematological evaluations of amyloid beta­induced Alzheimer's disease in rat.

Alzheimer's disease (AD) is a mental impairment and neural degeneration which causes progressive loss of memory and cognitive functions. This age­dependent illness is associated with extracellular amyloid plaques accumulation and twisted neurofibrillary tangles. Amyloid plaques are experimentally generated in animal models in order to investigate the disease process. In this study, we followed a rat model of AD for over a year. Wistar rats were divided randomly into two groups as control group (surgery without injection Aß), and experimental group (two­sided intrahippocampal amyloid­beta injection into hippocampus). From each group, three animals were investigated 42 days after injection, and the remaining four animals were studied after one year. All animals were tested for learning abilities and memory. Finally, samples from blood, brain, heart, kidney, liver, colon and spleen were examined. In the experimental group, the size of amyloid plaques were increased significantly after one year \\r\\nand learning abilities and memory were concomitantly decreased. Onsets of various other conditions such as liver and kidney disorders, diabetes, and metabolic syndrome were observed, which indicates that the animals may be prone to cardiovascular disorders and ischemia.

Thermal analysis of magnetic nanoparticle in alternating magnetic field on human HCT-116 colon cancer cell line.

PURPOSE: The purpose of this study was to closely investigate the effects of heat dissipation of superparamagnetic nanoparticles on HCT-116 human cancer cell lines cultured under laboratory conditions and also to examine important parameters including size and concentration of nanoparticles, magnetic field frequency, magnetic field intensity, and exposure time. MATERIALS AND METHODS: Conducting experimental tests required special hardware capable of producing an AC magnetic field with various frequencies. The design and construction process for such an experimental set-up is presented here. First, three different Fe3O4 nanoparticle sizes (8, 15 and 20 nm) with different concentrations (d = 10, 20, 40, 80, 160 and 200 µg/ml) were added to cell culture medium and the resulting mixture was exposed to an AC magnetic field with maximum amplitude of 10 kOe for 30 min under three operating frequencies (f = 80, 120 and 180 kHz). The level of intracellular iron was estimated by the ferrozine-based colorimetric assay. Three concentrations including 20, 40 and 80 µg/ml from each of the three nanoparticles sizes were chosen for the study. RESULTS: It was shown that the power dissipation is a function of frequency, time, nanoparticles size and dose. It was also found that the alternating magnetic field with three different frequencies (f = 80, 120 and 180 kHz) and the maximum amplitude of 10 kOe did not have any adverse effect on cell survival. CONCLUSIONS: Our results demonstrate that where thermal dose is equal to 4.5 ± 0.5 °C/30 min from a starting temperature of 37 °C, HCT-116 cell death is initiated when a magnetic nanoparticle electromagnetic field induced.