Apoptotic effect of melatonin on ER-positive breast cancer cell lines: ADGRL4 gene expression and promoter methylation.

Breast cancer (BC) is the second most common malignancy worldwide. ADGRL4, as a modulator of angiogenesis, undergoes various epigenetic modifications affecting its biological functions. In this study, we aimed to assess ADGRL4 promoter methylation status and its expression levels in primary breast tumors and to evaluate its potency as a plausible prognostic biomarker in BC. Furthermore, we evaluated the effect of melatonin on ADGRL4 expression and viability of BC cells in vitro. One hundred breast tumor tissue samples and adjacent non-tumor tissues were collected, followed by DNA isolation, bisulfite conversion, qRT-PCR, qMSP assay, and immunoblotting. In addition, four BC cell lines were treated with melatonin and subjected to ADGRL4 expression analysis and apoptosis assay. We found a significant correlation between ADGRL4 expression levels and HER2 status and stage of disease (P < 0.05). We observed a substantial attenuation in ADGRL4 promoter methylation in tumor samples compared to marginal non-tumor samples. A significantly lower expression of ADGRL4 was detected in two BC cell lines in the presence of melatonin. MCF-7 and BT474 melatonin-treated cell lines showed a significantly higher number of apoptotic cells than non-treated cells (P < 0.0001). Based on the receiver operating characteristic (ROC) curve analysis, ADGRL4 expression and ADGRL4 promoter methylation status showed moderate prognostic value. We found that melatonin has anti-cancer effects on BC cells. In addition, ADGRL4 expression can potentially be used as a prognostic biomarker in BC.

Three possible diagnostic biomarkers for gastric cancer: miR-362-3p, miR-362-5p and miR-363-5p.

Aim: MicroRNAs can be regarded as biomarkers for gastric cancer (GC) diagnosis in the early stages. This study assesses the expression levels of miR-362-3p, miR-362-5p and miR-363-5p as potential biomarkers for GC.Materials & methods: The expression levels of the miRNAs in 90 pairs of GC and adjacent normal tissue samples were analyzed by quantitative real-time reverse transcription PCR (qRT-PCR) and some bioinformatics tools were utilized for analyzing the target genes and possible molecular pathways in which these miRNAs participate.Results & conclusion: There was a significant overexpression of the miRNAs in GC cells and an outstanding correlation between their overexpression with some clinicopathological features of the patients.

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Investigating SNHG3 and BCYRN1 lncRnas expression in the peripheral blood cells of multiple sclerosis patients.

BACKGROUND: MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. METHODS: A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. RESULTS: Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02).Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). DISCUSSION: Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.

Reduction of ristocetin-induced platelet aggregation (RIPA) during storage despite plasma renewal: evidence for hemostatic importance of GPIbα shedding.

BACKGROUND: Platelet storage is complicated by deleterious changes, among which reduction of ristocetin-induced platelet aggregation (RIPA) has a poorly understood mechanism. The study elucidates the mechanistic roles of all the possible players in this process. RESEARCH DESIGN AND METHODS: PRP-platelet concentrates were subjected to RIPA, collagen-induced platelet aggregation (CIPA), and flowcytometric analysis of GPIbα and PAC-1 binding from days 0 to 5 of storage. Platelet-poor plasma was subjected to colorimetric assays for glucose/LDH evaluation and automatic analyzer to examine VWF antigen and activity. RESULTS: From day three of platelet storage, reducing CIPA but not RIPA was correlated with the reduction of both metabolic state and integrin activity. RIPA reduction was directly related to the decreased levels of total-content/expression of GPIbα, and inversely related to its shedding levels during storage. Re-suspension of 5-day stored platelet in fresh plasma compensated CIPA, but not RIPA. VWF concentration and its activity did not change during storage while they had no correlation with RIPA. CONCLUSIONS: This study identified the irreversible loss of platelet GPIbα, but not VWF status, as the primary cause of the storage-dependent decrease of RIPA. Unlike CIPA, this observation was not compensated by plasma refreshment, suggesting that some evidence of PSL may not be recovered after transfusion.

The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes-specific markers and inflammation in women with type 2 diabetes: A randomized double-blind placebo-controlled trial.

This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.

Upregulation of Long Noncoding RNA PCAT1 in Iranian Patients with Colorectal Cancer and Its Performance as a Potential Diagnostic Biomarker.

Background: Long noncoding RNAs (lncRNAs) as critical molecules play an essential role in the development of cancers. In colorectal cancer (CRC), various lncRNAs are related to cell proliferation, apoptosis, migration, and invasion. LncRNA prostate cancer-associated transcript 1 (PCAT-1), as an oncogenic factor, is a diagnostic biomarker that regulates cell proliferation, migration, invasion, and apoptosis. Methods: This study evaluated the relationship between PCAT-1, CRC occurrence, and pathological features of Iranian patients. The studied samples included 100 colorectal tumor tissues and 100 adjacent healthy tissues of Iranian CRC patients. RNAs were extracted from cancerous and noncancerous tissues to synthesize complementary DNA. The expression level of PCAT-1 was assessed using the real-time PCR method, and the data analysis was assessed using SPSS software. Results: In this study, expression level of PCAT-1 in tumor tissue was significantly increased in Iranian patients, and pathological studies of the patients had no significant relationship with the PCAT-1 expression profile. Conclusion: Our results suggested that the high expression of PCAT-1 resulted in the occurrence of colorectal tumor tissues in Iranian patients, which can be considered a diagnostic biomarker in CRC.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Border fences reduce potential for transboundary migration of Marco Polo Sheep (Ovis ammon polii) in the Pamir Plateau.

Border fences have severely impeded the transboundary migration of a number of large mammals worldwide, with central Asia being one of the most impacted. The Marco Polo sheep (Ovis ammon polii), an iconic species of Pamir, is threatened in its transboundary movement by increasing border fencing among their five distributed countries, including Tajikistan, Kyrgyzstan, China, Afghanistan, and Pakistan. In this study, by building ensemble species distribution models, we found that eastern Tajikistan had the largest suitable Macro Polo sheep habitat (about 42 % of the total suitable habitat), followed by China (about 32 %). We used least-cost paths to identify 51 ecological corridors including 5 transboundary ecological corridors, which may be important to maintain connectivity in both domestic and transboundary regions. To assess the potential barrier effect of border fences, we assessed four scenarios (30, 40, 50 and 60°) corresponding to the upper limit of the slope for the construction of fences. In areas too steep for fencing, these could be used by wild sheep to cross barriers or borders and may represent migration or movement routes, defined as natural passages. In the most pessimistic Scenario 60, only 25 migratory passages along the border fences were identified, compared to 997 in the most optimistic scenario (Scenario 30), indicating a strong negative effect of intensive border fencing on the transboundary movement of Marco Polo sheep. The establishment of transnational conservation parks, and ensuring permeability is maintained in key areas, could have a positive impact on the connectivity and persistence of Marco Polo sheep populations, and provide important lessons for other large migratory mammals in transboundary regions.

High-resolution assessment of the carrying capacity and utilization intensity in mountain rangelands with remote sensing and field data.

Dry rangelands provide resources for half of the world's livestock, but degradation due to overgrazing is a major threat to system sustainability. Existing carrying capacity assessments are limited by low spatiotemporal resolution and high generalization, which hampers applied ecological management decisions. This paper provides an example for deriving the carrying capacity and utilization levels for cold drylands at a new level of detail by including major parts of the transhumance system. We combined field data on vegetation biomass and communities, forage quality, productivity, livestock species and quantities, grazing areas and their spatiotemporal variations with Sentinel-2 and MODIS snow cover satellite imagery to develop maps of forage requirements and availability. These products were used to calculate carrying capacity and grazing potential in the Pamir-Hindukush Mountains. Results showed high spatial variability of utilization rates between 5% and 77%. About 30% of the area showed unsustainable grazing above the carrying capacity. Utilization rates displayed strong spatial differences with unsustainable grazing in winter pastures and at lower elevations, and low rates at higher altitudes. The forage requirements of wild herbivores (ungulates and marmots) were estimated to be negligible compared to livestock, with one tenth of the biomass consumption and no increase in unsustainably grazed pastures due to the wider distribution of animals. The assessment was sensitive to model parameterization of forage requirements and demand, whereby conservative scenarios, i.e. lower fodder availability or higher fodder requirements of livestock due to climate and altitude effects, increased the area with unsustainable grazing practices to 50%. The presented approach enables an in-depth evaluation of the carrying capacity and corresponding management actions. It includes new variables relevant for transhumance systems, such as the combination of forage quantity and quality or accessibility restrictions due to snow, and shows utilization patterns at high spatial resolutions. Regional maps allow the identification of unsustainable utilization areas, such as winter pastures in this study.

The effect of glatiramer acetate, IFNß-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients.

OBJECTIVE: Multiple sclerosis (MS) is a progressing neurodegenerative disease marked by chronic central nervous system inflammation and degeneration.This study investigates gene expression profiles of T-box transcription factor TBX21 (T-bet), interferon-gamma (IFN-γ), and long non-coding RNA MEG3 in peripheral blood mononuclear cells (PBMCs) from treatment-naïve Relapsing-Remitting Multiple Sclerosis patients (RRMS), healthy controls, and RRMS patients on different Disease Modifying Therapies (DMTs). The aim is to understand the role of T-bet, IFN-γ, and MEG3 in MS pathogenesis and their potential as diagnostic and therapeutic targets. RESULTS: Elevated T-bet expression is observed in treatment-naïve RRMS patients compared to healthy individuals. RRMS patients treated with Interferon beta-1alpha (IFNß-1a) and fingolimod exhibit downregulated T-bet and MEG3 expression levels, respectively, with more pronounced effects in females. Healthy individuals show a moderate positive correlation between T-bet and MEG3 and between IFN-γ and T-bet. In RRMS patients treated with Glatiramer Acetate (GA), a strong positive correlation is observed between MEG3 and IFN-γ. Remarkably, RRMS patients treated with Dimethyl Fumarate (DMF) exhibit a significant positive correlation between T-bet and MEG3. These findings underscore the diagnostic potential of T-bet in RRMS, warranting further exploration of MEG3, T-bet, and IFN-γ interplay in RRMS patients.

MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.

Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis-given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.

Study of LncRNA BANCR Expression in Tumor Tissues and Adjacent Normal Tissues in Gastric Cancer Patients.

Background: Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including cancer development and progression. This study aimed to investigate the expression differences of the BRAF-activated non-coding RNA (BANCR) gene in GC tissues compared to adjacent normal tissues. The potential diagnostic significance of BANCR in GC was explored, with the aim of improving diagnostic and therapeutic approaches for this global health burden. Materials and Methods: Tissue samples from 100 gastric cancer (GC) patients were collected, and BANCR expression was analyzed using quantitative real-time PCR. Correlations between BANCR expression and clinicopathological features were assessed, and its biomarker potential was evaluated. Results: In individuals diagnosed with GC, the expression of BANCR was notably elevated in tumor tissues compared to adjacent normal tissues (P < 0.0001). However, the analysis of gene expression data did not demonstrate any statistically significant correlation between elevated BANCR expression and clinicopathological features. According to the ROC analysis, BANCR demonstrated an AUC of 0.6733 (P < 0.0001), with a sensitivity of 73% and a specificity of 45%. However, further evaluation is required to determine its potential as a biomarker (CI 95% = 0.5992 to 0.7473). Conclusions: The observed upregulation of BANCR in GC tissues implies its potential involvement as an oncogenic lncRNA in GC patients. Furthermore, BANCR may serve as a promising biomarker for identification and treatment of GC.

Expression Level of lncRNA CYTOR in Iranian Cervical Cancer Patients.

Background: A critical role has been known for lncRNAs in the initiation and development of cancers. Therefore, lncRNAs have been reported as the possible biomarkers in relation to the diagnosis and therapy of malignancies. This project examined the change in CYTOR lncRNA expression in human cervical cancer samples as compared with adjacent healthy ones. Methods: We provided one hundred fifteen pairs of tumorous and adjacent healthy tissue specimens of cervical cancer patients. RNAs were isolated from tissue specimens and cDNAs were synthesized. We considered quantitative Real-time PCR (qRT-PCR) to examine the expression levels of CYTOR lncRNA. In addition, the biomarker activity of CYTOR and the associations between the lncRNA and clinicopathological characteristics were evaluated. Results: The significant increased expression of CYTOR was obtained in cancerous samples as compared with non-cancerous ones (P< 0.0001). A significant correlation was indicated between CYTOR expression and the squamous subtype of cervical cancer (p=0.046). The receiver operating characteristic (ROC) curve-related AUC (area under the curve), specificity, and sensitivity were calculated 0.88, 81.74%, and 80%, respectively, which may introduce CYTOR as a potential biomarker. Conclusion: CYTOR may be an effective oncogene and biomarker in cervical cancer cases given its increased expression in human cervical cancer tissues.

Emerging roles of miR-145 in gastrointestinal cancers: A new paradigm.

Gastrointestinal (GI) carcinomas are a group of cancers affecting the GI tract and digestive organs, such as the gastric, liver, bile ducts, pancreas, small intestine, esophagus, colon, and rectum. MicroRNAs (miRNAs) are small functional non-coding RNAs (ncRNAs) which are involved in regulating the expression of multiple target genes; mainly at the post-transcriptional level, via complementary binding to their 3'-untranslated region (3'-UTR). Increasing evidence has shown that miRNAs have critical roles in modulating of various physiological and pathological cellular processes and regulating the occurrence and development of human malignancies. Among them, miR-145 is recognized for its anti-oncogenic properties in various cancers, including GI cancers. MiR-145 has been implicated in diverse biological processes of cancers through the regulation of target genes or signaling, including, proliferation, differentiation, tumorigenesis, angiogenesis, apoptosis, metastasis, and therapy resistance. In this review, we have summarized the role of miR-145 in selected GI cancers and also its downstream molecules and cellular processes targets, which could lead to a better understanding of the miR-145 in these cancers. In conclusion, we reveal the potential diagnostic, prognostic, and therapeutic value of miR-145 in GI cancer, and hope to provide new ideas for its application as a biomarker as well as a therapeutic target for the treatment of these cancer.

Expression pattern of PCAT1, PCAT2, and PCAT5 lncRNAs and their value as diagnostic biomarkers in patients with gastric cancer.

BACKGROUND: Gastric cancer (GC), is a complex multifactorial neoplasm with a high mortality and prevalence rate all over the world. Hence, it is necessary to identify the multiple pathways that are previously unknown and are involved in its initiation and progression. Recently, it has become clear that long non-coding RNAs (lncRNAs) play a crucial role in the onset and spread of cancer. The current study assessed the lncRNAs PCAT1, PCAT2, and PCAT5 expression in primary gastric tumors and adjacent noncancerous tissues. METHODS: 90 pairs of GC and adjacent noncancerous tissue samples were obtained. Total RNA was extracted, then cDNA was synthesized. Using quantitative reverse transcriptase PCR (qRT-PCR), PCAT1, PCAT2, and PCAT5 expression levels were evaluated. Using the SPSS statistical package, the correlation between clinicopathological characteristics and the expression of PCAT1, PCAT2, and PCAT5 was investigated. The diagnostic value of PCAT1, PCAT2, and PCAT5 in GC was assessed using the receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to surrounding non-cancerous tissues, PCAT1, PCAT2, and PCAT5 were all significantly overexpressed in tumoral tissues (P = 0.001, P = 0.019, and P = 0.0001, respectively). PCAT5 expression was significantly associated with gender (P = 0.020), according to our research. The ROC curve's findings indicated that PCAT1, PCAT2, and PCAT5 may each function as poor diagnostic biomarkers, with respective AUC values of 64 %, 60 %, and 68 %, specificity values of 68 %, 60 %, and 76 %, and sensitivity values of 55 %, 72 %, and 52 %. CONCLUSION: Our research suggested that PCAT1, PCAT2, and PCAT5 may be engaged in promoting and developing GC cells as a novel oncogene because of the increased expression of PCAT1, PCAT2 and PCAT5 in tumor tissues of GC patients. Additionally, PCAT1, PCAT2, and PCAT5 can be thought of as poor diagnostic biomarkers for GC case detection.

Up-regulation of BOK-AS1, FAM215A and FEZF1-AS1 lncRNAs and their potency as moderate diagnostic biomarkers in gastric cancer.

BACKGROUND: Gastric cancer is the fifth most frequent cancer worldwide and the fourth leading cause of death from cancer, a complex multifactorial neoplasm. LncRNAs are regulatory RNA molecules larger than 200 nucleotides, which can have profound effects on the oncogenic process of various types of cancer. Therefore, these molecules can be used as diagnostic and therapeutic biomarkers. This study aimed to determine the differences in BOK-AS1, FAM215A, and FEZF1-AS1 gene expression between tumor tissue and adjacent healthy non-tumor tissue of gastric cancer (GC) patients. METHODS: In this study one hundred pairs of cancerous and non-cancerous marginal tissues were gathered. Next, RNA extraction and cDNA synthesis were achieved for all of the samples. Then, the qRT-PCR was performed to measure the expression of BOK-AS1, FAM215A and FEZF1-AS1 genes. RESULTS: All BOK-AS1, FAM215A and FEZF1-AS1 genes showed significantly increased expression in tumor tissues compared with non-tumor tissues. The outcome of the ROC analysis demonstrated that BOK-AS1, FAM215A, and FEZF1-AS1 may act as mean biomarkers with AUC of 0.7368, 0.7163 and 0.7115, specificity of 64%, 61% and 59%, and sensitivity of 74%, 70%, and 74% respectively. CONCLUSION: Based on the increased expression of the BOK-AS1, FAM215A and FEZF1-AS1 genes in GC patients, this study suggests that these genes may function as oncogenic factors. Furthermore, the mentioned genes can be considered as intermediate biomarkers for diagnosis and treatment of gastric cancer. In addition, no association between these genes and clinicopathological features was observed.

The Effect of Ferrule/Crown Ratio and Post Length on the Applied Stress and Strain Distribution to the Endodontically Treated Maxillary Central Teeth: A Finite Element Analysis.

Objectives: One of the most common methods used for the reconstruction of endodontically treated teeth is post and core and crown. Various factors such as the remaining tissue above the cutting margin (ferrule) affect the fracture resistance of teeth restored with post and core and crown. This study aimed to investigate the effect of ferrule/crown ratio (FCR) on the strength of maxillary anterior central teeth using finite element analysis. Materials and Methods: A 3D scan of a central incisor was obtained, and the data were transferred to Mimics software. Then, a 3D model of the tooth was designed. Next, 300N load was applied at a 135° angle to the tooth model. Force was applied to the model both horizontally and vertically. Ferrule height was considered to be 5%, 10%, 15%, 20%, and 25% in the palatal surface and 50% in the buccal surface. The length of post in the model was 11, 13, and 15mm. Results: By increasing the FCR, stress and strain distribution increased in the dental model and decreased in the post itself. As the horizontal angle of load application increased, the level of stress and strain created in the dental model increased as well. The closer the force application site to the incisal area, the higher the stress and strain would be. Conclusion: Maximum stress was inversely correlated with FCR and post length. In ratios of 20% and higher, insignificant changes occurred in stress and strain patterns in the dental model.

Apoptosis and myocardial infarction: role of ncRNAs and exosomal ncRNAs.

ncRNAs, particularly miRNAs, lncRNAs and circRNAs, are a group of RNAs which, although they do not encode proteins (however, recent evidence shows that certain circRNAs are translatable), play a major role in regulating gene expression and, therefore, affect multiple cellular processes, in particular apoptosis. Apoptosis is proven to mediate myocardial infarction physiopathology in addition to ischemic necrosis and, therefore, has recently gained great interest as a target to improve MI outcomes. The current work reviews studies that have assessed ncRNAs with the ability to promote or suppress apoptosis in the process of MI and, therefore, may introduce new therapeutic targets for MI treatment.

Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells.

Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.

Alterations in the expression levels of long intergenic non-coding RNA APOC1P1-3 in cervical cancer tissue samples.

lncRNAs play a crucial role in the carcinogenesis process. Thus, they have been recognized as the potential therapeutic and diagnostic biomarkers of cancers. This study assessed the alteration in the expression of APOC1P1-3 lncRNA in cancerous tissues compared to their adjacent non-tumorous tissues sampled from cervical cancer patients. one hundred fifteen pairs of cancerous and adjacent non-cancerous biopsy of cervical cancer specimens were collected. RNA isolation and cDNA synthesis were carried out. The qRT-PCR was used to assess the changes in the expression of APOC1P1-3 lncRNA. Moreover, the biomarker function of the lncRNA and the correlations between APOC1P1-3 and clinicopathological parameters were measured. The APOC1P1-3 expression was significantly increased in cervical cancer specimens as compared to adjacent non-tumorous specimens (p < 0.0001). A significant association was also observed between APOC1P1-3 expression and lymph node involvement (p = 0.031). Additionally, APOC1P1-3 expression demonstrated a significant association with the depth of tumor invasion (p = 0.035), and squamous type of cervical cancer (p = 0.019). The overexpression of APOC1P1-3 was significantly observed in patients younger than 50 years old as compared to another age group (p = 0.033). The results of ROC curve exhibited that APOC1P1-3 with area under the curve (AUC), specificity, and sensitivity of 0.96, 93.91%, and 78.26%, respectively can be considered as a potential biomarker. Regarding overexpression of APOC1P1-3 in human cervical cancer samples, this lncRNA may be considered as an oncogenic factor in cervical cancer patients. Besides, APOC1P1-3 may be a possible biomarker for the diagnosis and treatment of cervical cancer patients.