Background/Aim: Long non-coding RNAs (lncRNAs) such as NEAT1, HULC, and MALAT1, which are expressed in adipose tissue, are known to play a role in regulating adiposity. However, how the plasma expression of these lncRNAs changes in obese patients following rapid adipose tissue loss after sleeve gastrectomy remains unclear. This study aimed to investigate the relationship between plasma NEAT1, HULC, and MALAT1 expression levels and short-term weight loss after sleeve gastrectomy. Materials and Methods: Plasma samples prospectively collected from patient groups were used for total RNA extraction to measure the expression levels of NEAT1, HULC, and MALAT1 both before sleeve gastrectomy and 30 days after the procedure. Additionally, patients were followed for changes in body mass index (BMI) and HbA1C levels over a 12-month period. Associations between lncRNA expression levels and clinical parameters were evaluated. Results: Before sleeve gastrectomy, the expression levels of NEAT1 and HULC were significantly higher in obese patients compared to non-obese individuals (p < 0.0001). Sleeve gastrectomy was associated with decreased expression levels of NEAT1 (p = 0.004) and HULC (p = 0.0027). NEAT1 and HULC expression levels showed significant associations with changes in HbA1C and BMI, respectively (p < 0.05). Conclusions: NEAT1 and HULC expression levels were associated with short-term metabolic and anthropometric changes following sleeve gastrectomy. These findings are exploratory and hypothesis-generating, and further studies with larger cohorts and longer follow-up are needed to determine their potential clinical relevance.

Objectives:Glioblastoma (GB) is the most aggressive type of brain tumor in adults, and the chemical agent temozolomide (TMZ) is widely used for its treatment. However, TMZ resistance can lead to therapeutic failure. The aim of this study was to investigate the effect of the bioflavonoid fisetin on GB cell growth and on overcoming TMZ resistance in TMZ-sensitive, inherited-resistant, and acquired-resistant GB cells the effect of fisetin on TMZ efficacy evaluin primary GB cells. Materials and Methods:GB cell lines (T98G; intrinsic TMZ-resistant, A172; TMZ-sensitive, A172-R; acquired TMZ-resistant) and primary GB cells derived from patient samples were treated with effective doses of TMZ (ranging from 900 to 1000 μM), fisetin (ranging from 13.78 to 16.40 μM), or a combination of both. TMZ resistance was acquired in A172 cells through stepwise increases in TMZ concentration. Real-time cell proliferation was measured using the xCELLigence system. The migratory capacity of the cells was evaluated using a wound-healing assay. The RNA expression of the epithelial-to-mesenchymal transition (EMT)-inducing transcription factor E-box-binding homeobox 1 (ZEB1) was assessed by quantitative polymerase chain reaction. Cell assays were analyzed by analysis of variance, and ZEB1 expression was analyzed by t-test. Results:Fisetin substantially enhanced the effect of TMZ in all the cell lines included in the present study, as evidenced by significant decreases in cell proliferation and wound-healing, and in ZEB1 expression (p<0.0001). In addition, TMZ+fisetin reduced ZEB1 expression in primary GB tumors but not in butterfly GB cells. Conclusion:Fisetin alone was effective against GB; importantly, the TMZ+fisetin combination demonstrated greater efficacy than TMZ alone by enhancing sensitivity to TMZ through downregulation of ZEB1 in various resistant models, including patient-derived samples. Since ZEB1 is associated with EMT and drug resistance, fisetin may be a promising anticancer candidate to improve chemotherapeutic efficacy in resistant GB and to shed light on personalized treatments, pending further preclinical research.

Ph-like ALL, a high-risk subgroup of B-cell ALL, is associated with a poor prognosis. The genetic diversity observed across different ethnicities underscores the importance of population-specific studies to gain a deeper understanding of its genetic drivers and clinical outcomes. This study aims to characterize the Ph-like ALL group in Turkish pediatric B-ALL patients and evaluate our custom-developed gene panel for subgroup identification. To identify the Ph-like subgroup, RNA was isolated from 35 bone marrow samples, and targeted mRNA expression analysis was performed by RT-qPCR using a custom-designed panel consisting of 96 genes. Additionally, the Archer FusionPlex ALL Panel (ArcherDX, Boulder, CO) was employed for further evaluation of patients demonstrating the highest similarity rates. This study employed a gene panel designed to differentiate Turkish Ph-like ALL patients within the Ph-negative group, identifying two Ph-like cases (6%). The panel demonstrated 96.9% sensitivity and 93.9% specificity in detecting Ph-like ALL, highlighting its effectiveness in differential diagnosis. In the Ph-like cases, alterations in PAX5 (rs143723948, rs879020782) and IKZF1 (rs6975767) were observed. Both cases shared a novel EPOR variant (rs1312770718), with no known clinical impact. Additionally, a novel variantin the PTPN11 gene was interpreted as "Possibly Damaging". This study introduces a gene profiling-based diagnostic approach for the Ph-like subgroup of pediatric B-ALL in Turkish patients. The integration of targeted tyrosine kinase inhibitors into treatment protocols, guided by the diagnostic algorithm, aims to improve prognosis and survival, advancing personalized management of Ph-like ALL.

Glioblastoma (GB) is an aggressive brain tumor characterized by extensive heterogeneity. We aimed to generate patient-derived GB organoids preserving histological features and to establish a biobank for future studies. Materials and Methods: Tumor tissues from GB patients were dissected into 0.5–1 mm fragments and cultured for 14 days in organoid medium under orbital shaking. Immunohistochemical analysis was performed to assess GFAP, OLIG2, IDH-1, p53, ATRX, and Ki67 expression before and after organoid formation. Results: All tumor samples formed spherical organoids within 14 days. Histological analysis showed preservation of GB-specific morphological features, including nuclear atypia and pleomorphism. GFAP, OLIG2, and ATRX expression patterns were concordant between parental tumors and organoids in cases. IDH-1 expression was consistent in three patients. Ki67 and p53 expression levels showed similar patterns between organoids and corresponding tumors. Conclusion: Patient-derived GB organoids retain key histopathological features and may serve as a platform for GB modeling.

Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive pediatric CNS malignancies characterized by SMARCB1 loss, which leads to the dysregulated expression of Enhancer of Zeste Homolog 2 (EZH2), a key catalytic component of the Polycomb Repressive Complex 2 (PRC2). This dysregulation results in aberrant trimethylation of histone H3 at lysine 27 (H3K27me3), driving tumor progression. While EZH2 inhibitors like tazemetostat are in clinical use, their efficacy remains limited, necessitating a deeper understanding of PRC2 regulation. We investigated the role of long non-coding RNAs (lncRNAs) in modulating the EZH2-PRC2 axis in AT/RT. Expression levels of lncRNAs (MALAT1, ANRIL, KCNQ1OT1) were analyzed via RT-PCR in 10 archival AT/RT patient tissues. RNA immunoprecipitation (RIP) was performed to identify direct interactions with EZH2. The functional impact of MALAT1 inhibition on H3K27me3 levels, mesenchymal markers (CDH2, TWIST, ZEB1), and tumorigenic behaviors (migration, invasion, sphere formation) was evaluated in vitro. MALAT1, ANRIL, and KCNQ1OT1 were significantly overexpressed in AT/RT tissues (p < 0.05). RIP assays revealed that only MALAT1 directly interacts with EZH2 in DAOY and primary AT/RT cells. MALAT1 knockdown significantly reduced H3K27me3 levels (p < 0.05) and markedly impaired cell migration, invasion, and sphere-forming capacity. These phenotypic changes were associated with the downregulation of key mesenchymal markers (CDH2, TWIST, ZEB1). Our findings identify MALAT1 as a critical epigenetic regulator in AT/RT that interacts with EZH2 to maintain the PRC2-mediated repressive landscape. Targeting the MALAT1-EZH2 axis provides a novel translational perspective to enhance the efficacy of epigenetic therapies in AT/RT. MALAT1 is significantly upregulated in AT/RT and correlates with aggressive clinicopathological features. MALAT1 physically interacts with EZH2, sustaining the H3K27me3 repressive landscape in patient-derived cells. Inhibition of the MALAT1-EZH2 axis reverses the mesenchymal phenotype and impairs tumor sphere growth. EZH2 inhibition triggers a compensatory increase in MALAT1, suggesting a novel feedback loop and resistance mechanism. Dual targeting of MALAT1 and EZH2 represents a promising therapeutic strategy for pediatric rhabdoid tumors.

Glioblastoma (GB), the most aggressive type of brain tumor, has a poor prognosis. In this study, we aimed to develop a drug delivery system that can be used in GB treatment with the bioactive compounds oleuropein (OL) and its derivative hydroxytyrosol (HT) loaded into mesoporous silica nanoparticles (MSNs) and to investigate their anticancer effects on GB cells. MSNs were synthesized via a sol‒gel method, followed by surface grafting of azetidine to introduce hyperbranched polypropylene imine (PPI) groups, increasing the particle stability and OL/HT loading efficiency. OL and HT-loaded MSN-PPI nanocarriers (MSN-PPI@OL and MSN-PPI@HT) were characterized, and their effects on tumor aggressiveness were evaluated in T98G cells. The results showed that the nanocarriers presented a positive surface charge and hydrodynamic sizes between 300 and 500 nm, with effective concentrations above 100 µg/mL. MSN-PPI@OL and MSN-PPI@HT alone and in combination with temozolomide (TMZ) inhibited cell migration (p < 0.0001), reduced the expression of epithelial‒mesenchymal transition (EMT) markers (p < 0.05), and suppressed angiogenesis (p < 0.0001). In the colony formation assays, the MSN-PPI nanocarriers had stronger antiproliferative effects than did TMZ (p < 0.0001) and suppressed the expression of stem cell markers (p < 0.05). Additionally, these treatments decreased LOXL1-AS1, PVT1, and MALAT1 expression (p < 0.05) and reduced global cell viability (p < 0.0001). In conclusion, these findings suggest the potential of MSN-PPI@OL and MSN-PPI@HT as effective therapeutic strategies for GB.

In this study, bioactive and biocompatible transdermal patches were fabricated through the lyophilization of a chitosan/carboxymethylcellulose/akermanite composite matrix. The influence of curcumin incorporation at 0.5%, 1%, and 2% on the physicochemical, morphological, and biological properties of the patches was systematically investigated. Scanning electron microscopy revealed an interconnected porous structure with pore sizes ranging from 29 to 57 mu m, facilitating cell infiltration and nutrient transport. Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy confirmed the successful integration of akermanite and curcumin, along with characteristic interactions within the polymeric network. In vitro release studies demonstrated a biphasic profile consisting of an initial burst followed by a sustained release phase, with the CCMAKCur0.5 sample achieving the highest cumulative release (94.28%). Antioxidant performance, evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, ranged from 21.55% (CCM) to 38.96% (CCMAKCur0.5), while higher curcumin concentrations reduced activity due to increased matrix densification. Simulated body fluid immersion confirmed apatite formation, particularly in CCMAKCur0.5 and CCMAKCur2, indicating enhanced bioactivity. Cytocompatibility studies with HUVECs showed no toxic effects, and scratch assays demonstrated that CCMAKCur0.5 most effectively promoted wound closure. Overall, the findings indicate that curcumin- and akermanite-loaded lyophilized patches represent promising candidates for transdermal therapeutic applications.

Surgery is one of the most effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). Despite the widespread application of surgical approaches, recurrence rates remain substantial. Although chemotherapy is frequently employed, the supporting evidence for its efficacy in this context remains inconclusive. In the present study, we aimed to identify potential predictors of post-metastasectomy recurrence by analyzing clinical, pathological, and molecular features of both primary colorectal tumors and their corresponding hepatic metastases. Specifically, we evaluated the expression of epithelial-mesenchymal transition (EMT) markers, cancer stem cell (CSC) markers, and selected oncogenic mRNAs (RAS, mTOR, and CMYC) in tissue samples from 84 patients. RAS and CMYC are well-known proto-oncogenes involved in cell proliferation and survival, while mTOR functions as a central regulator of cell growth and metabolism. Following liver metastasectomy, intra-hepatic recurrence was observed in 40.5% of the cases. Among the molecular markers analyzed, the EMT transcription factor SNAIL-which plays a critical role in cancer cell invasion and metastasis-and mTOR exhibited significantly elevated expression in metastatic lesions from patients who experienced recurrence. While SNAIL expression did not show a clear association with the time to recurrence, increased mTOR expression in metastatic liver tissue was significantly associated with both shorter recurrence-free survival and diminished overall survival (p < 0.001). Results showed that mTOR expression levels could be a clinically relevant predictive indicator of remnant liver recurrence. In patients with liver metastases, the use of mTOR inhibitors may be considered after hepatic metastasectomy.

OBJECTIVES:This study was conducted to examine the dose-related effects over time of oleuropein on the proliferation and area of tumor spheroids in hepatocellular carcinoma cells.MATERIALS AND METHODS:We examined the possible effects of 100 to 500 μM dose concentrations of oleuropein on HepG2 cell proliferation using a real-time cell analyzer. A 3-dimensional hepatocellular carcinoma tumor spheroid model was established by seeding HepG2 cells at a density of 160 cells/well in custom 96-well microplates with low attachment surfaces and culturing for 3 days. Tumor spheres were treated with increasing oleuropein doses for 72 hours, and images were captured every 24 hours. The dose-dependent effects of oleuropein on tumor sphere size were analyzed by measuring the area of tumor spheres with ImageJ software. We conducted oleuropein viability and cytotoxicity analyses using calcein acetoxymethyl ester-based and propidium iodide-based staining in the tumor model.RESULTS:Oleuropein inhibited cell proliferation; as the dose concentration of oleuropein increased, so did its capacity to inhibit cell proliferation (P < .001). The size of untreated tumor spheres increased at 72 hours (P < .001). However, treatment with 100 to 500 μM oleuropein reduced tumor size by 63.56% to 88.06% compared with untreated cells at the end of 72 hours (P < .001). With increasing concentrations, oleuropein inhibited the viability of tumor spheres, eliminating necrotic death caused by tumor hypoxia.CONCLUSIONS:Overall, oleuropein reduced the size of tumors by inhibiting tumor proliferation and viability. In this context, oleuropein could be a candidate molecule for further extensive studies to reduce hepatocellular carcinoma tumors to meet Milan criteria for liver transplant.

Background. Congenital lung malformations (CLMs) refer to structural abnormalities of the lungs that occur during fetal development. Matrix metalloproteinases (MMPs) constitute a group of zinc-dependent enzymes, with certain members of this family playing pivotal roles in the remodeling of the lungs both prenatally and postnatally. This study aimed to explore expression levels of MMP-2, MMP-7, and MMP-9 in CLMs which are recognized as pivotal contributors to their clinical pathology. Methods. A total of 41 patients between the ages of 0-17 years that had undergone lung surgery for CLMs between March 2007- July 2023 were analyzed. The demographic features, clinical and pathological findings were recorded. The expression levels of MMP-2, MMP-7 and MMP-9 in patients’ tissues were examined by reverse transcription polymerase chain reaction and compared in CLMs and adjacent normal lung tissues. Results. Among patients with CLMs, 12 patients had congenital pulmonary airway malformations (CPAM, one patient had bilateral lesions), 18 patients had bronchopulmonary sequestration (BPS), 7 patients had congenital lobar overinflation (CLO), and 4 patients had bronchogenic cyst (BC). The higher expression of MMP-7 and MMP-9 in all CLM tissues compared to normal tissue was observed. But, there was a trend in MMP-2 expression in CPAM tissues and MMP-2 showed high expression in the BPS, CLO and BC groups, which was not statistically significant. Upon collective analysis of all groups, it was observed that mRNA expressions of MMP-7 and MMP-9 exhibited greater upregulation in CPAM and BC in comparison to BPS and CLO. Conclusions. Our findings indicate a specific involvement of MMP-7 and MMP-9 in the pathogenesis of CLMs, particularly in CPAM and BC. To the best of our knowledge, this research represents the initial demonstration of MMP expression in CLMs.

Objective: This research explores the regulation of SLC2A3 and NLRP3 genes in cancers of the head and neck region, including oral squamous cell carcinoma (OSCC), focusing on their contribution to tumor progression and the regulatory effects of specific miRNAs. Methods: SLC2A3 and NLRP3 gene expressions in HNSC were analyzed using the GEPIA database with TCGA and GTEx data. Protein-protein interactions were predicted via the STRING database, while miRNA-mRNA interactions were examined using miRDB. RT-qPCR was used to analyze gene expression in tissue samples obtained from 50 individuals with OSCC and 6 non-cancerous controls, while miRNA levels were measured using TaqMan™ Advanced miRNA Assays. Statistical analyses included t-tests, ANOVA, and Kaplan-Meier survival analysis. Results: SLC2A3 levels were markedly elevated in HNSC tumor samples relative to non-cancerous tissues (p = 0.01) and showed a progressive increase with advancing tumor stages (p = 0.0059). NLRP3 expression was found to be higher in HNSC (p = 0.01) without any significant association with tumor progression. In OSCC, both SLC2A3 and NLRP3 expressions increased with tumor stage and were strongly correlated (p < 0.0001). Elevated NLRP3 was associated with reduced survival rates (p = 0.0001). miR-22 and miR-30e levels decreased with tumor progression and were linked to poor survival (p

Metastasectomy of liver metastases of colorectal cancer (CRC) offers the greatest likelihood of cure. Nevertheless, recurrence rates after this procedure are high, and chemotherapy is a reasonable choice with inconclusive evidence. In our study, we aimed to investigate the parameters that can be used to predict the development of recurrence after metastasectomy by examining clinical, pathological and molecular markers in primary tumor and their liver metastases.

Infliximab (IFX) is widely used in the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Still, long-term use may be ineffective or suggest some side effects. This study investigated the role of Myricetin, a flavonoid, alone and its complementary therapeutic potential in combination with IFX against UC, CH, and cancerization. DSS triggered the development of acute UC syndromes in Wistar albino rats, while TNBS treatment triggered some of the symptoms seen in CD. The effectiveness of IFX, Myricetin, and their combination against UC and CD was determined by the disease activity index and changes in TNF-α secretion. The effect of IFX and Myricetin on tumor aggressiveness was evaluated by in vitro wound healing and colony formation analysis and expression of NF-κB and COX2 genes in a colon cancer cell line. Myricetin strongly reduced NF-κB expression in the DSS-induced UC model (p < 0.0001), but this effect was weaker in the TNBS-induced CD model, while COX2 expression was the opposite. Myricetin was beneficial as a complement to IFX in the CD model, while also promoting the improvement of clinical symptoms of the acute UC model (p < 0.05). Myricetin slowed down wound healing and colony formation of HT-29 cells and attenuated NF-κB expression. Myricetin may promise an alternative treatment approach in acute UC. Additionally, CD cases may benefit from Myricetin only when used in conjunction with IFX.

The overall survival of patients with the advanced and recurrent gastric cancer (GC) remains unfavorable. In particular, this is due to cancer spreading and resistance to chemotherapy associated with the epithelial-mesenchymal transition (EMT) of tumor cells. EMT can be identified by the transcriptome profiling of GC for EMT markers. Indeed, analysis of the TCGA and GTEx databases (n = 408) and a cohort of GC patients (n = 43) revealed that expression of the CDH2 gene was significantly decreased in the tumors vs. non-tumor tissues and correlated with the overall survival of GC patients. Expression of the EMT-promoting transcription factors SNAIL and ZEB1 was significantly increased in GC. These data suggest that targeting the EMT might be an attractive therapeutic approach for patients with GC. Previously, we demonstrated a potent anti-cancer activity of the olive leaf extract (OLE). However, its effect on the EMT regulation in GC remained unknown. Here, we showed that OLE efficiently potentiated the inhibitory effect of the chemotherapeutic agents 5-fluorouracil (5-FU) and cisplatin (Cis) on the EMT and their pro-apoptotic activity, as was demonstrated by changes in the expression of the EMT markers (E- and N-cadherins, vimentin, claudin-1) in GC cells treated with the aforementioned chemotherapeutic agents in the presence of OLE. Thus, culturing GC cells with 5-FU + OLE or Cis + OLE attenuated the invasive properties of cancer cells. Importantly, upregulation of expression of the apoptotic markers (PARP cleaved form) and increase in the number of cells undergoing apoptosis (annexin V-positive) were observed for GC cells treated with a combination of OLE and 5-FU or Cis. Collectively, our data illustrate that OLE efficiently interferes with the EMT in GC cells and potentiates the pro-apoptotic activity of certain chemotherapeutic agents used for GC therapy.

Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber network (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHNTMZ and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHNTMZ+rutin, significantly reduced sphere size compared to untreated and LHNTMZ-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHNTMZ+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHNTMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHNTMZ+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHNTMZ+rutin is a promising biocompatible model for the local treatment of GB.

Objective: We hypothesized that microRNAs (miRNAs) might be involved in tumor development by critically regulating cancer stem cell (CSC) markers in the early stages of colon cancer (eCC). This study aimed to determine the expression profiles of miRNAs in CSC-positive eCC patients and examine their associations with recurrence. Materials and Methods: We analyzed CD133, LGR5 and SOX2 expression profiles to determine CSC status in 30 eCC specimens. Then, using the results of RT2 miRNA PCR custom arrays, we evaluated the expression profiles of 38 miRNAs in CSC-positive eCC patients. Results: Recurrence occurred in 5 patients within ten years after surgery. We determined down-regulation of miR-125b and up-regulation of miR-135b were significant in CSC-positive eCC patients (p=0.021, p=0.001, respectively). We found that low expression of miR-125b was associated with recurrence in eCC (p=0.0022). Conclusions: We suggest that recurrence might be prevented by increasing the expression of miR-125b in eCC.

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) coreshell nanofiber webs were encapsulated with OL (PLA(OL)), rutin (PLA(rutin)), and TMZ (PLA(TMZ)) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core -shell structures with an average diameter between 133 +/- 30.7-139 +/- 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA(OL) and PLA(TMZ) suppressed GB cell viability with a controlled release that increased over 120 h, while PLA(rutin) caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nanowebs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Introduction: Recent research into multiple sclerosis (MS) has focused on the role of microRNAs (miRNAs) in the development of the disease. This study was designed to analyze miR-146a expression in whole blood and fecal samples of patients with MS. The study aimed to analyze clinical data using the miR-146a expression values obtained. Subjects and Methods: This study included patients with relapsing–remitting MS (RRMS) (n = 53), clinically isolated syndrome (CIS) (n = 15), and healthy controls (n = 26). Total RNA was isolated from the participants' whole blood and fecal samples. RNA extraction was performed using QIAamp RNA Blood Mini Kits for blood samples and RNeasy PowerMicrobiome Kits for feces. miR-146a expressions were studied using real-time polymerase chain reaction. Finally, relative expression was correlated with clinicopathologic factors. Results: MiR-146a expression was significantly decreased in the whole blood (P < 0.001) and fecal samples (P = 0.036) of patients with RRMS. There was no significant difference in the miR-146a expression rate between patients with CIS and controls. Moreover, the miR-146a expression level in patients with RRMS was decreased compared with those with CIS (P < 0.001). A significant association was determined between miR-146a expression and sex in blood samples. When sex stratification was applied to expression values obtained from fecal samples, miR-146a expression was downregulated only in females (P = 0.008). Discussion: miRNAs play an essential role in maintaining the stable course of MS, and this process has some sex-specific differences. Expression of fecal miR-146a may be used as a biomarker to diagnose and predict prognosis in patients with RRMS.

AIM:To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM).MATERIAL AND METHODS:Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction.RESULTS:The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression.CONCLUSION:Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.