Differential expression of two genes Oct-4 and MUC5AC associates with poor outcome in patients with gastric cancer.

Gastric cancer (GC) is the most frequent leading cause of cancer-associated mortality worldwide that is linked to poor prognosis due to the lack of appropriate biomarkers. Our aim was to evaluate the MUC5AC and Oct-4 expression levels in GC and to assess their association with clinical factors. Immunohistochemical analysis (IHC) and qRT-PCR were performed in GC patients to examine the MUC5AC and Oct-4 expression levels. The mRNA level of MUC5AC was significantly decreased in tumour tissues compared with non-cancerous tissues (1.11 ± 0.69 vs 3.7 ± 0.71; P = .024). On the other hand, Oct-4 mRNA level was upregulated in tumour tissues as compared to normal tissues (2. 86 ± 0.78 vs 0.87 ± 0.54; P = .0015). Decreased expression of MUC5AC was detected in 27 patients (67.5%), while high to moderate expression levels were observed in 13 cases (32.5%), but in normal tissues the expression levels of MUC5AC were increased (P = .001). The decreased expression of MUC5AC was associated with aggressive tumour characteristics, such as TNM stage (P = .023), histologic type (P = .012) and lymph node metastasis (P = .001). High expression of Oct-4 was detected in 24 tumour tissues (60%), while 16 cases (40%) showed low expression level. Increased Oct-4 expression was correlated with clinicopathological characteristics such TNM stage (P = .002), histologic type (P = .008) and lymph node metastasis (P = .001). Our results showed that high Oct-4 expression and the reduction of MUC5AC expression may be involved in the progression and an unfavorable prognosis of GC.

In Vitro Transportation of Curved Canals Following Glide Path Preparation by Path File and Scout RaCe Rotary Systems versus Manual Instrumentation Using Cone-Beam Computed Tomography.

Objectives: This study aimed to assess root canal transportation of curved canals following glide path preparation by PathFile and Scout RaCe rotary systems compared with manual instrumentation with stainless steel (SS) hand files using cone-beam computed tomography (CBCT). Materials and Methods: This in-vitro experimental study was conducted on extracted human mandibular first and second molars (n=51) with 25-45° canal curvature in their mesiobuccal root. All teeth underwent CBCT and were randomly divided into three groups (n=17). In group 1, a glide path in the mesiobuccal canal was created using SS hand files to the working length. In groups 2 and 3, after canal negotiation with a #8 SS hand file, a glide path was created with PathFile and Scout RaCe systems, respectively. The teeth underwent CBCT. Pre- and postoperative CBCT scans were compared to calculate the magnitude of canal transportation at 3, 6, and 9 mm from the apex. The results were analyzed using the Kruskal-Wallis and Freedman tests (P<0.05). Results: Manual instrumentation caused significantly higher canal transportation at 3 and 9 mm from the apex compared with rotary systems (P<0.05). PathFile and Scout RaCe were not significantly different at 3 (P=0.39) or 9 mm (P=0.99). No significant difference was noted in canal transportation among the three groups at 6 mm (P=0.15). Conclusion: Scout RaCe and PathFile cause less canal transportation than manual instrumentation with SS files when used for glide path preparation in curved canals, especially in the apical third.

Polymeric-based microneedle arrays as potential platforms in the development of drugs delivery systems.

BACKGROUND: Microscopic patches as quite promising platforms in transdermal drug delivery suffer from conventional injections. In other hand, a wide range of pharmacokinetics, ranging from fast oral administration to sustained drug delivery, can be implemented with the help of microneedle arrays (MNAs). AIM OF REVIEW: Hence, in this paper, we overviewed different kinds of MNAs such as solid/coated, hollow, porous, hydrogel/swellable, and merged-tip geometry followed by introducing different types of material (silicon, glass, ceramics, dissolving and biodegradable polymers, and hydrogel) used for fabrication of MNAs. Afterwards, some conventional and brand-new simple and customizable MN mold fabrication techniques were surveyed. Polymeric MNAs have received a great deal of attention due to their potential biocompatibility and biodegradability in comparison to other materials. Therefore, we also covered different kinds of polymers such as hydrogel/swellable, dissolving and biodegradable analogues used for the development of MNAs as potential candidates in drug delivery systems (DDSs). Finally, we discussed different challenges and future perspectives in the aspect of MNAs-based drug delivery platforms. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review may provide guidelines for the rational design of polymeric MNAs-based DDSs for promising programmable drug release and enhanced therapeutic effect.

Enzyme immobilization onto the nanomaterials: Application in enzyme stability and prodrug-activated cancer therapy.

Nanoparticles (NPs) have been widely used for immobilization of wide ranges of enzymes. However, the stabilization of enzymes on NPs is a major challenge, crucial for regulating enzymatic activity and their medical applications. To overcome these challenges, it is necessary to explore how enzymes attach to nanomaterials and their properties are affected by such interactions. In this review we present an overview on the different strategies of the enzyme immobilization into the NPs and their corresponding stability against temperature and pH. The effects of surface charge, particle size, morphology, and aggregation of NPs on the stability of immobilized enzymes were summarized. The activity of immobilized enzyme into the NPs was reviewed to disclose more detail regarding the interaction of biomolecules with NPs. The combination of enzyme immobilization with prodrugs was also reviewed as a promising approach for biomedical application of enzyme in cancer therapy. Finally, the current challenges and future applications of NPs in enzyme immobilization and the utilization of immobilized enzyme toward prodrug activation in cytoplasm of cancer cells were presented. In conclusion, this review may pave the way for providing a perspective on development to the industrial and clinical translation of immobilized enzymes.

Up-regulation of miR-130b expression level and down-regulation of miR-218 serve as potential biomarker in the early detection of human osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity that principally emerges in children and adolescents. MiRNAs regulate a variety of normal physiologic processes and are involved in tumorigenesis and development of multiple malignancies, including OS. This study was aimed to evaluate the clinical significance of miR-130b and miR-218 in osteosarcoma patient. METHODS: We utilized quantitative real-time PCR to evaluate the level of miR-130b and miR-218 expressions in OS patients and normal tissues and their relationship with clinicopathological features and survival in OS patients. RESULTS: QRT-PCR indicated that miR-130b expression in tumor tissues was strongly elevated than adjacent non-tumor tissues (P < 0.001), while the level of miR-218 expression in osteosarcoma tissues was down-regulated than adjacent non-tumor tissues (P < 0.001). We evaluated the clinical significance of miR-130b and miR-218 in osteosarcoma. Clinical correlation analysis showed that increased expression of miR-130b and decreased expression of miR-218 were significantly associated with advanced tumor stage (x (2) = 6.285, P < 0.009; x (2) = 7.172, P < 0.007), distant metastasis (x (2) = 5.528; P < 0.001; x (2) = 4.617, P < 0.001) and size of tumor (x (2) = 5.01, P = 0.013; x (2) = 4.271, P = 0.019). CONCLUSIONS: Taken together, our data indicated that high miR-130b level and low level of miR-218 are associated with poor clinicopathological characteristics. Furthermore, miR-130b may play a key role in the progression of osteosarcoma.

Down-regulated MicroRNA 148b expression as predictive biomarker and its prognostic significance associated with clinicopathological features in non-small-cell lung cancer patients.

BACKGROUND: Lung cancer is most common and is the leading cause of cancer-related death in both men and women worldwide. Understanding of the molecular mechanisms underlying non-small cell lung cancer (NSCLC) development and progression are important. In the present study, we investigated the potential role of miR-148b expression analysis as potential lung cancer biomarker with the correlation of circulating miR-148b to clinicopathological features. METHODS: A total of 104 NSCLC patients were diagnosed and cancer tissues together with adjacent normal tissues were evaluated. Quantitative Real-time PCR method was utilized to evaluate the expression levels of miR-148b. In addition, we investigated to clarify the relationship of miR-148b with clinicopathological features and survival in patients with NSCLC. RESULTS: Our findings showed that miR-148b was downregulated in tumor tissues when compared with corresponding adjacent normal lung tissues (0.34 ± 0.13 vs. 1.00 ± 0.57, P < 0.05). Moreover decreased expression of miR-148b was significantly related to TNM stage (P = 0.001) and lymph node-metastasis (P = 0.023). This findings suggested that miR-148b was down-regulated in NSCLC patients and may play a key role as a tumor suppressor gene in NSCLC. Kaplan-Meier survival analysis and log-rank test suggested that low-expression group of patients had significantly shorter overall survival than high-expression group (log-rank test: P = 0.031). Multivariate Cox proportional hazards model analysis indicated that low miR-148b expression was independently linked to poor survival of patients with NSCLC (HR = 3.215, 95 % CI: 1.543-10.621, P = 0.021) and other factors were not significant independent predictor of survival in patients with NSCLC. CONCLUSION: Our findings demonstrated that miR-148b may play a role as independent prognostic factor for patients with NSCLC.