Reactive oxygen species (ROS) with strong oxidizing and high activity have been regarded as an effective “weapon” for antitumor therapy, since it can induce organelle injury, oxidative damage, and cell death. Herein, hollow structured manganese carbonate (MnCO3) nanocubes are fabricated and loaded with photosensitizer (chlorin e6, Ce6), obtaining a responsive nanoplatform H-MnCO3/Ce6-PEG (HMCP NCs). Two different approaches to upregulate intracellular ROS level were realized by HMCP NCs. On one hand, with irradiation of external laser, Ce6 could generate singlet oxygen (1O2) through a multistep photochemical process applied in photodynamic therapy (PDT). On the other hand, MnCO3 could be specifically degraded into Mn2+ in an acidic tumor microenvironment (TME), triggering Mn2+-activated Fenton-like reaction to convert endogenous H2O2 into hydroxyl radical (•OH). In vitro combined chemodynamic therapy (CDT) and PDT showed that the metal ion-enhanced ROS production could break the intracellular redox equilibrium, thus leading to cell death. In vivo combined CDT/PDT with HMCP NCs exhibited remarkably enhanced therapeutic efficacy in inhibiting tumor growth, without resulting in noticeable damage to normal tissues. This work presents a unique type of manganese-based nanoplatform for efficiently generating ROS in solid tumors, favorable for ROS-involved therapeutic strategies.

Gastric cancer is one of the most common types of human cancer associated with a poor prognosis. MicroRNAs (miRs), a class of non-coding RNAs that are 18–25 nucleotides in length, act as key regulators in gene expression, and have been implicated in various human cancer types. miR-125b has been implicated in the malignant progression of gastric cancer. However, the association between miR-125b expression, clinicopathological characteristics and trastuzumab resistance in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains unclear. In the current study, in situ hybridization data demonstrated that 81.8% (108/132) of gastric cancer tissues exhibited positive expression of miR-125b, while only 26.3% (10/38) of non-tumor gastric tissues were miR-125b-positive. Reverse transcription-quantitative polymerase chain reaction data indicated that the expression level of miR-125b was markedly increased in gastric cancer tissues compared with non-cancerous gastric tissues. Furthermore, the miR-125b level was significantly associated with tumor (T) stage, lymph node metastasis, distant metastasis and TNM stage of gastric cancer (P<0.05). Increased miR-125b expression predicated poor prognosis in patients with gastric cancer. For HER2-positive gastric cancer, the upregulation of miR-125b expression was significantly associated with advanced malignant progression, as well as a poor prognosis (P<0.05). Furthermore, data from the present study indicated that the increased miR-125b level was significantly associated with trastuzumab resistance in HER2-positive gastric cancer (P<0.05). Therefore, the current study suggests that miR-125b may become a potential biomarker for predicting prognoses and clinical outcomes in patients with HER2-positive gastric cancer that receive trastuzumab treatment.

The aim of this study was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorders (ASD) by measuring serum circulating levels of BDNF as well as calcium and comparing them with age-matched and sex-matched normal controls. The study included 75 drug-naive ASD children and 75 age-sex-matched healthy children. The concentration of serum BDNF was determined using the enzyme-linked immunosorbent assay method at baseline. Clinical information was collected. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean serum BDNF levels were significantly (P<0.0001) higher in children with ASD compared with the control cases (17.59±5.55 vs. 11.21±2.79 ng/ml; t=8.902). On the basis of the receiver operating characteristic curve, the optimal cutoff value of serum BDNF levels as an indicator for auxiliary diagnosis of autism was projected to be 12.65 ng/ml, which yielded a sensitivity of 80.8% and a specificity of 70.2%; the area under the curve was 0.840 [95% confidence interval (CI), 0.777-0.904]. In univariate logistic regression analysis, with an unadjusted odds ratio of 9.42 (95% CI, 4.33-25.95; P<0.0001), BDNF of 12.65 ng/ml or more had an association with a diagnosis of ASD. After adjusting for possible covariates, BDNF of 12.65 ng/ml or more is still an independent indicator of ASD, with an adjusted odds ratio of 7.33 (95% CI, 2.98-16.55; P<0.0001). Serum BDNF levels may be associated independently with the severity of ASD, and higher BDNF levels could be considered an independent diagnostic marker of ASD.

MicroRNAs (miRs) have been demonstrated to regulate various biological processes in human cancer, including non-small cell lung cancer (NSCLC). However, little evidence has been provided regarding the exact role of miR-200c in mediating the malignant progression of NSCLC, as well as the underlying mechanism. The present study aimed to investigate the putative role of miR‑200c in the progression of NSCLC. The expression levels of miR‑200c were significantly reduced in NSCLC cell lines compared with in normal lung epithelial cells, as determined by reverse transcription‑quantitative polymerase chain reaction. Overexpression of miR‑200c significantly suppressed cell migration and invasion of A549 NSCLC cells. Results of a luciferase reporter assay further identified zinc finger E‑box‑binding homeobox 2 (ZEB2) as a direct target gene of miR‑200c, and the expression of ZEB2 was shown to be suppressed in A549 cells overexpressing miR‑200c. Furthermore, small interfering RNA‑mediated inhibition of ZEB2 suppressed the migration and invasion of A549 cells. In addition, since ZEB2 is an epithelial‑mesenchymal transition (EMT) regulator, the role of miR‑200c in the regulation of EMT in NSCLC cells was further examined. Results of a western blot analysis indicated that overexpression of miR‑200c upregulated E‑cadherin, and downregulated N‑cadherin and vimentin expression in A549 cells, thus suggesting that EMT was suppressed. Based on these results, the present study suggested that miR‑200c was able to inhibit the metastasis of NSCLC cells by targeting ZEB2. Therefore, miR-200c may be considered as a potential candidate for the treatment of NSCLC.

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