Dysregulated microRNAs in prostate cancer: In silico prediction and in vitro validation.

Objectives: MicroRNAs, which are micro-coordinators of gene expression, have been recently investigated as a potential treatment for cancer. The study used computational techniques to identify microRNAs that could target a set of genes simultaneously. Due to their multi-target-directed nature, microRNAs have the potential to impact multiple key pathways and their pathogenic cross-talk. Materials and Methods: We identified microRNAs that target a prostate cancer-associated gene set using integrated bioinformatics analyses and experimental validation. The candidate gene set included genes targeted by clinically approved prostate cancer medications. We used STRING, GO, and KEGG web tools to confirm gene-gene interactions and their clinical significance. Then, we employed integrated predicted and validated bioinformatics approaches to retrieve hsa-miR-124-3p, 16-5p, and 27a-3p as the top three relevant microRNAs. KEGG and DIANA-miRPath showed the related pathways for the candidate genes and microRNAs. Results: The Real-time PCR results showed that miR-16-5p simultaneously down-regulated all genes significantly except for PIK3CA/CB in LNCaP; miR-27a-3p simultaneously down-regulated all genes significantly, excluding MET in LNCaP and PIK3CA in PC-3; and miR-124-3p could not down-regulate significantly PIK3CB, MET, and FGFR4 in LNCaP and FGFR4 in PC-3. Finally, we used a cell cycle assay to show significant G0/G1 arrest by transfecting miR-124-3p in LNCaP and miR-16-5p in both cell lines. Conclusion: Our findings suggest that this novel approach may have therapeutic benefits and these predicted microRNAs could effectively target the candidate genes.

Downregulation of salivary miR-3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus.

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease.

BACKGROUNDS: Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25 % of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD. MiRNAs are potential therapeutic agents that can regulate several genes simultaneously. Therefore, we transfected cell lines with two key miRNAs involved in targeting NAFLD-related genes. METHODS: The suppression effects of the investigated miRNAs (miR-124 and miR-16) and genes (TNF, TLR4, SCD, FASN, SREBF2, and TGFß-1) from our previous study were investigated by real-time PCR in Huh7 and HepG2 cells treated with oleic acid. Oil red O staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were utilized to assess cell lipid accumulation and cytotoxic effects of the miRNAs, respectively. The pro-oxidant-antioxidant balance (PAB) assay was undertaken for miR-16 and miR-124 after cell transfection. RESULTS: Following transfection of miRNAs into HepG2, oil red O staining showed miR-124 and miR-16 reduced oleic acid-induced lipid accumulation by 35.2 % and 28.6 % respectively (p < 0.05). In Huh7, miR-124 and miR-16 reduced accumulation by 23.5 % and 31.3 % respectively (p < 0.05) but without impacting anti-oxidant activity. Real-time PCR in HepG2 revealed miR-124 decreased expression of TNF by 0.13-fold, TLR4 by 0.12-fold and SREBF2 by 0.127-fold (p < 0.05). miR-16 decreased TLR4 by 0.66-fold and FASN by 0.3-fold (p < 0.05). In Huh7, miR-124 decreased TNF by 0.12-fold and FASN by 0.09-fold (p < 0.05). miR-16 decreased SCD by 0.28-fold and FASN by 0.64-fold (p < 0.05). MTT assays showed, in HepG2, viability was decreased 24.7 % by miR-124 and decreased 33 % by miR-16 at 72 h (p < 0.05). In Huh7, miR-124 decreased viability 42 % at 48 h and 29.33 % at 72 h (p < 0.05), while miR-16 decreased viability by 32.3 % (p < 0.05). CONCLUSION: These results demonstrate the ability of miR-124 and miR-16 to significantly reduce lipid accumulation and expression of key pathogenic genes associated with NAFLD through direct targeting. Though this requires further in vivo investigation.

Clinical value and potential circulating of miR-99a as tumor suppressor biomarker in serum of oral squamous cell carcinoma and erosive atrophic lichen planus.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasms that consist of more over 90% of oral cancers. It was demonstrated that erosive atrophic oral lichen planus (OLP) has potential of malignancy transformation into OSCC. The microRNAs are non-coding regulator sequences involved in cancer process. The miR-99a involve in growth, proliferation, migration, invasion, and metastasis of tumor cells. Therefore, we evaluated miR-99a expression in serum of OSCC and erosive atrophic OLP patients in comparison to healthy control individuals to more investigate about level of miR-99a expression in potential premalignant disorder (erosive atrophic OLP) in comparison to malignant transformation form (OSCC). Gene ontology (GO) and pathway analyses were performed to better understand the importance of miR-99a in OSCC. MATERIALS AND METHODS: In this cross-sectional study, total 90 serum samples from OSCC patients (n = 30), erosive atrophic OLP (n = 30) and healthy control individuals (n = 30) were collected, and then evaluated for miR-99a expression by qPCR. Pathway analysis and protein-protein interaction were done using STRING (v: 12.0), and (GO) terms and related genes were extracted from the GO online search tool. The statistical analysis was evaluated by Kruskal Wallis, Chi-Square, Kruskal Wallis, Spearman and Mann-Whitney tests. The p-value less than 0.05 was considered statistically significant. RESULTS: miR-99a expression down regulated in OSCC in comparison to erosive atrophic OLP and control groups (p < 0.05). The miR-99a up regulated in grade I more than grades II and III (p < 0.05). We showed upregulation of miR-99a in early stage more than advanced stage (p < 0.05). Expression of miR-99a reduced accordance to the increasing of tumor size and lymph involvement levels (p < 0.05). The 165 determined targets were classified into three domains. The most significant enrichment in biological processes, cellular components, and molecular functions was in the cellular nitrogen compound biosynthetic process, cytosolic ribosome, and protein binding, respectively. CONCLUSIONS: We highlighted tumor suppressive role of miR-99a in OSCC patients. It seems that miR-99a can be considered a valuable biomarker for the early diagnosis of erosive atrophic OLP before transformation. CLINICAL RELEVANCE: Our results may help to better understand the prognostic factor for oral squamous cell carcinoma to evaluate survival and subsequent tumor development. And it may also help to understand the pathogenesis of OSCC.

Unveiling the Potential of Serum MiR-483-5p: A Promising Diagnostic and Prognostic Biomarker in OLP and OSCC Patients by In silico Analysis of Differential Gene Expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.

MiR-548c-3p through suppressing Tyms and Abcg2 increases the sensitivity of colorectal cancer cells to 5-fluorouracil.

Background: Colorectal cancer, is one of most prevalent the cancer in the world. 5-Fluorouracil is a standard chemotherapeutic drug while the acquisition of resistance to 5-Fluorouracil is one of the problems during treatment. In this study, we aimed to find the miRNAs that modulate the expression of Tyms and Abcg2 as resistance-inducing genes in the resistant cell lines to 5-Fluorouracil. Methods: 5-Fluorouracil-resistant HCT116 and SW480 cell lines were generated by consecutive treatment of cells with 5-Fluorouracil. This resistance induction was validated by MTT assays. The expression of the Tyms and Abcg2 gene and miR-548c-3p were studied by quantitative real-time PCR in the cell lines. Results: We hypothesized that miR-548c-3p is targeting Tyms and Abcg2 simultaneously. Increased expression Tyms gene in the two most resistant cell lines derived from HCT116 and all resistant cell lines derived from SW480 except one were seen. Increased expression of Abcg2 was observed in the most resistant HCT116-derived cell line and all resistant cell lines, derived from SW480. In all resistant cell lines, the expression of miR-548c-3p was decreased. Conclusion: It can be concluded downregulation of miR548c-3p is in line with Tyms and Abcg2 overexpression in resistant cell lines to 5-Fluorouracil.

Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies.

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC.

A label-free electrochemical biosensor based on PBA-Au-MXene QD for miR-122 detection in serum samples.

A poly(n-butyl acrylate)-gold-MXene quantum dots (PBA-Au-MXene QD) nanocomposite-based biosensor is presented that is modified by unique antisense single-stranded DNA (ssDNA) and uses the electrochemical detection methods of DPV, CV, and EIS to early detect miR-122 as a breast cancer biomarker in real clinical samples. This fabrication method is based on advanced nanotechnology, at which a poly(n-butyl acrylate) (PBA) as a non-conductive polymer transforms into a conductive composite by incorporating Au-MXene QD. This biosensor had a limit of detection (LOD) of 0.8 zM and a linear range from 0.001 aM to 1000 nM, making it capable of detecting the low concentrations of miR-122 in patient samples. Moreover, it allows approximately 100% sensitivity and 100% specificity for miR-122 without extraction. The synthesis and detection characteristics were evaluated by different complementary tests such as AFM, FTIR, TEM, and FESEM. This new biosensor can have a high potential in clinical applications to detect breast cancer early and hence improve patient outcomes.

Melatonin Attenuates Arsenic-Induced Neurotoxicity in Rats Through the Regulation of miR-34a/miR-144 in Sirt1/Nrf2 Pathway.

Arsenic (As) exposure is known to cause several neurological disorders through various molecular mechanisms such as oxidative stress, apoptosis, and autophagy. In the current study, we assessed the effect of melatonin (Mel) on As-induced neurotoxicity. Thirty male Wistar rat were treated daily for 28 consecutive days. As (15 mg/kg, gavage) and Mel (10 and 20 mg/kg, i.p.) were administered to rats. Morris water maze test was done to evaluate learning and memory impairment in training days and probe trial. Oxidative stress markers including MDA and GSH levels, SOD activity, and HO-1 levels were measured. Besides, the levels of apoptosis (caspase 3, Bax/Bcl2 ratio) and autophagy markers (Sirt1, Beclin-1, and LC3 II/I ratio) as well as the expression of miR-144 and miR-34a in cortex tissue were determined. As exposure disturbed learning and memory in animals and Mel alleviated these effects. Also, Mel recovered cortex pathological damages and oxidative stress induced by As. Furthermore, As increased the levels of apoptosis and autophagy proteins in cortex, while Mel (20 mg/kg) decreased apoptosis and autophagy. Also, Mel increased the expression of miR-144 and miR-34a which inhibited by As. In conclusion, Mel administration attenuated As-induced neurotoxicity through anti-oxidative, anti-apoptotic, and anti-autophagy mechanisms, which may be recommended as a therapeutic target for neurological disorders.

Chromosomal Instability in Various Generations of Human Mesenchymal Stem Cells Following the Therapeutic Radiation.

Background: Radiotherapy is a crucial treatment for most malignancies. However, it can cause several side effects, including the development of secondary malignancies due to radiation-induced genomic instability (RIGI). The aim of this study was to evaluate genomic instability in human mesenchymal stem cells (hMSCs) at different X-ray radiation doses. Additionally, the study aimed to examine the relative expression of certain genes involved in DNA repair, proto-oncogenes, and tumor suppressor genes. Methods: After extracting, characterizing, and expanding hMSCs, they were exposed to X-ray beams at doses of 0, 0.5, 2, and 6 Gy. Nuclear alterations were evaluated through the cytokinesis-block micronucleus (CBMN) assay at 2, 10, and 15 days postirradiation. The expressions of BRCA1, BRCA2, TP53, Bax, Bcl2, and KRAS genes were analyzed 48 hr after irradiation to evaluate genomic responses to different radiation doses. Results: The mean incidence of micronuclei, nucleoplasmic bridges, and nuclear buds was 4.8 ± 1.6, 47.6 ± 6, and 18 ± 2.6, respectively, in the nonirradiated group 48 hr after the fourth passage, per 1,000 binucleated cells. The incidence of micronuclei in groups exposed to 0.5, 2, and 6 Gy of radiation was 14.3 ± 4.9, 32.3 ± 6.5, and 55 ± 9.1, respectively, 48 hr after irradiation. The expression levels of the BRCA2, Bax, TP53, and KRAS genes significantly increased after exposure to 6 Gy radiation compared to the control groups. However, there was no significant increase in BRCA1 and Bcl2 gene expression in our study. Conclusion: This study demonstrated significant nuclear alterations in the 10 days postirradiation due to the RIGIs that they inherited from their irradiated ancestral cells. While chromosomal instability is a prevalent event in malignant cells, so it seems necessary to optimize radiotherapy treatment protocols for tissues that contain stem cells, especially with IMRT, which delivers a low dose to a larger volume of tissues.

Deciphering colorectal cancer progression features and prognostic signature by single-cell RNA sequencing pseudotime trajectory analysis.

Colorectal cancer is the third most common cancer and second cancer with the highest mortality rate in the world. Progression, which leads to metastasis, is one of the biggest challenges in cancer treatment, and despite improvement in screening and treatment techniques, 5 years of survival of colorectal cancer patients drop from 91% in stage I to 12% in stage IV. Single-cell RNA sequencing is one of the most powerful tools to study complex diseases such as cancer, and despite its recent emergence, it's rapidly growing. In contrast to bulk RNA sequencing, which averages out expression of thousands of cells, single-cell RNA sequencing can capture intra-tumor heterogeneity. Moreover, cellular dynamic events like progression can be studied by pseudotime trajectory analysis of single-cell RNA sequencing data. Herein we used Samsung Medical Center (SMC) colorectal cancer single-cell RNA sequencing dataset to find important tumor epithelial cells subtypes. Subsequently, we've found important genes with a dynamic pattern along cancer progression by using pseudo-time trajectory analysis. Also, we found TGFB1 and IL1B as effective ligands and several transcription factors which may regulate the expression of pseudo-time related genes. In the end, we've constructed a LASSO cox regression using 20 psudotime genes, which can predict 3-year survival of colorectal cancer patients with AUC >0.7.

Design of a rapid electrochemical biosensor based on MXene/Pt/C nanocomposite and DNA/RNA hybridization for the detection of COVID-19.

Since the rapid spread of the SARS-CoV-2 (2019), the need for early diagnostic techniques to control this pandemic has been highlighted. Diagnostic methods based on virus replication, such as RT-PCR, are exceedingly time-consuming and expensive. As a result, a rapid and accurate electrochemical test which is both available and cost-effective was designed in this study. MXene nanosheets (Ti3C2Tx) and carbon platinum (Pt/C) were employed to amplify the signal of this biosensor upon hybridization reaction of the DNA probe and the virus's specific oligonucleotide target in the RdRp gene region. By the differential pulse voltammetry (DPV) technique, the calibration curve was obtained for the target with varying concentrations ranging from 1 aM to 100 nM. Due to the increase in the concentration of the oligonucleotide target, the signal of DPV increased with a positive slope and a correlation coefficient of 0.9977. Therefore, at least a limit of detection (LOD) was obtained 0.4 aM. Furthermore, the specificity and sensitivity of the sensors were evaluated with 192 clinical samples with positive and negative RT-PCR tests, which revealed 100% accuracy and sensitivity, 97.87% specificity and limit of quantification (LOQ) of 60 copies/mL. Besides, various matrices such as saliva, nasopharyngeal swabs, and serum were assessed for detecting SARS-CoV-2 infection by the developed biosensor, indicating that this biosensor has the potential to be used for rapid Covid-19 test detection.

Inducing apoptosis by using microRNA in radio-resistant prostate cancer: an in-silico study with an in-vitro validation.

BACKGROUND: One of the problems with radiation therapy (RT) is that prostate tumor cells are often radio-resistant, which results in treatment failure. This study aimed to determine the procedure involved in radio-resistant prostate cancer apoptosis. For a deeper insight, we devoted a novel bioinformatics approach to analyze the targeting between microRNAs and radio-resistant prostate cancer genes. METHOD: This study uses the Tarbase, and the Mirtarbase databases as validated experimental databases and mirDIP as a predicted database to identify microRNAs that target radio-resistant anti-apoptotic genes. These genes are used to construct the radio-resistant prostate cancer genes network using the online tool STRING. The validation of causing apoptosis by using microRNA was confirmed with flow cytometry of Annexin V. RESULTS: The anti-apoptotic gene of radio-resistant prostate cancer included BCL-2, MCL1, XIAP, STAT3, NOTCH1, REL, REL B, BIRC3, and AKT1 genes. These genes were identified as anti-apoptotic genes for radio-resistant prostate cancer. The crucial microRNA that knockdown all of these genes was hsa-miR-7-5p. The highest rate of apoptotic cells in a cell transfected with hsa-miR-7-5p was (32.90 ± 1.49), plenti III (21.99 ± 3.72), and the control group (5.08 ± 0.88) in 0 Gy (P < 0.001); also, this rate was in miR-7-5p (47.01 ± 2.48), plenti III (33.79 ± 3.40), and the control group (16.98 ± 3.11) (P < 0.001) for 4 Gy. CONCLUSION: The use of this new treatment such as gene therapy to suppress genes involved in apoptosis can help to improve the treatment results and increase the quality of life of patients with prostate cancer.

Screening and introduction of key cell cycle microRNAs deregulated in colorectal cancer by integrated bioinformatics analysis.

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. Impaired cell cycle regulation leads to many cancers and is also approved in CRC. Therefore, cell cycle regulation is a critical therapeutic target for CRC. Furthermore, miRNAs have been discovered as regulators in a variety of cancer-related pathways. This study is designed to investigate how miRNAs and mRNAs interact to regulate the cell cycle in CRC patients. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Expression Omnibus (GEO), and Therapeutic Target Database (TTD), cell cycle-associated genes were identified and evaluated. Seven of the 22 differentially expressed genes (DEGs) implicated in the cell cycle in three GSEs (GSE24514, GSE10950, and GSE74604) were identified as potential therapeutic targets. Then, using PyRx software, we performed docking proteins with selected drugs. The results demonstrated that these drugs are appropriate molecules for targeting cell cycle DEGs. Tarbase, miRTarbase, miRDIP, and miRCancer databases were used to find miRNAs that target the indicated genes. The ability of these six miRNAs to impact the cell cycle in colorectal cancer may be concluded. These miRNAs were found to be downregulated in SW480 cells when compared to the normal tissue. Our data imply that a precise selection of bioinformatics tools can facilitate the identification of miRNAs that impact mRNA translation at different stages of the cell cycle. The candidates can be investigated more as targets for cell cycle arrest in cancers.

Harnessing the Therapeutic Potential of Antimicrobial Peptides for Cancers: State of the Art.

Despite significant breakthroughs in cancer treatment, cancer remains a serious global health concern that takes thousands of lives each year. Still, drug resistance and adverse effects are the main problems in conventional cancer therapeutic approaches. Thus, the discovery of new anticancer agents with distinct mechanisms of action is a critical requirement that offers significant obstacles. Antimicrobial peptides (AMPs), which can be found in various forms of life, are recognized as defensive weapons against infections of microbial pathogens. Surprisingly, they are also capable of killing a variety of cancer cells. These powerful peptides can cause cell death in the gastrointestinal, urinary tract, and reproductive cancer cell lines. To emphasize the anti-cancer properties of AMPs, we summarize the research that examined their impact on cancer cell lines in this review.

Compositional and functional properties of high-density lipoproteins in relation to coronary in-stent restenosis.

Introduction: In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. Material and methods: This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. Results: No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Conclusions: Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study.

Melatonin ameliorates arsenic-induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats.

Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre-treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As-mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down-regulated autophagy markers such as Beclin-1 expression and the LC3-II/I ratio. Moreover, the cardiac expression of cleaved-caspase-3 and Bax/Bcl-2 ratio was decreased by Mel pretreatment. Reduced expression of miR-34a and miR-144 by As were reversed by Mel. The histopathological changes of cardiac injury associated with As exposure was moderated by Mel. Mel may improve As-induced cardiac dysfunction through anti-oxidative, anti-apoptotic, and anti-autophagic mechanisms.

A novel electrochemical biosensor based on signal amplification of Au HFGNs/PnBA-MXene nanocomposite for the detection of miRNA-122 as a biomarker of breast cancer.

Cancer is one of the leading causes of death worldwide and a crisis for global health. Breast cancer is the second most common cancer globally. In the perusal, a novel electrochemical biosensor amplified with hierarchical flower-like gold, poly (n-butyl acrylate), and MXene (AuHFGNs/PnBA-MXene) nanocomposite and activated by highly special antisense ssDNA (single-stranded DNA) provide a promising alternative for miRNA-122 detection as a biomarker of breast cancer. The biosensor presented a detection limit of 0.0035 aM (S/N = 3) with a linear range from 0.01 aM to 10 nM. The platform was tried on 20 breast cancer miRNAs extracted from actual serum specimens (10 positives and 10 negatives). Founded on the quantitatively obtained outcomes and statistic analysis (t-test, box-graph, receiver performance characteristic curve, and cut-off amount), the biosensor showed a meaningful discrepancy between the native and positive groups with 100% specificity and 100% sensitivity. While, RT-qPCR showed less specificity and sensitivity (70% specificity, 100% sensitivity) than the proposed biosensor. To assess the quantitative capacity and biosensor detection limit for clinical tests, the biosensor diagnosis performance for continually diluted miRNA extracted from patients was compared to that gained by RT-qPCR results, indicating that the biosensor detection limit was lower than RT-qPCR. ssDNA/AuHFGN/PnBA-MXene/GCE displayed little cross-reaction with other sequences and also showed desirable stability, reproducibility, and specificity and stayed stable until 32 days. As a result, the designed biosensor can perform as a hopeful method for diagnosis applications.