The mortality rate of ovarian cancer is the highest among gynecological tumors. The two factors leading to high mortality of ovarian cancer are late clinical stage and chemotherapy resistance. It is very important to reverse or intervene chemotherapy resistance. Abnormal circadian rhythm is related to the occurrence of tumor, and circadian clock protein PERIOD2 (PER2) acts as a tumor suppressor in cancer; however, little is known about its involvement in chemosensitivity.

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.

Human intake of selenium (Se) mainly occurs through the food chain, and is largely dependent on the bioavailability of soil Se. Sulfur (S) and phosphorus (P) also as essential nutrients for plants, their antagonistic with Se effects on Se bioavailability should be considered. We conducted pot experiments to investigate the interaction effect on the bioavailability of Se in the soil using a sequential extraction method and diffusive gradients in thin films (DGT). The results showed that the root and shoot Se of pak choi increased at most 340%-360% with S and P application, while the Se uptake by pak choi was slightly inhibited when S and P application was 100 mg kg-1. With high S and P application, pak choi Se had a high bioaccumulation factor (BAF) and low translocation factor (TF), and soil Soluble-Se (SOL-Se) increased 178%-299%, which due to the competitive adsorption of S, P with Se and changes in soil pH that lead to the transformation of soil Se fractions. In addition, the available Se concentration in soil measured by the DGT (CDGT-Se) increased by 866% with exogenous S and P application, and its source was HA-Se. However, CDGT-Se failed to show a good linear relationship with the Se content of pak choi. The application of DGT to assess the bioavailability of Se in soils where Se is present in the steady state needs to be further explored. We discuss the effect of S and P application on the bioavailability of soil Se and provide evidence for agricultural production and rational fertilizer use on Se-rich land.

microRNAs are a type of small non-coding RNAs which play important roles in post-transcriptional gene regulation, and the characterization of microRNA expression profiling in peripheral blood mononuclear cells (PBMCs) from patients with Klinefelter syndrome requires further investigation. In this study, PBMCs were obtained from patients with Klinefelter syndrome and normal controls. After preparation of small RNA libraries, the two groups of samples were sequenced simultaneously using next generation high-throughput sequencing technology, and novel and known microRNAs were analyzed. A total of 9,772,392 and 9,717,633 small RNA reads were obtained; 8,014,466 (82.01%) and 8,104,423 (83.40%) genome-matched reads, 64 and 49 novel microRNAs were identified in the library of Klinefelter syndrome and the library of healthy controls, respectively. There were 71 known microRNAs with differential expression levels between the two libraries. Clustering of over-represented gene ontology (GO) classes in predicted targets of novel microRNAs in the Klinefelter syndrome library showed that the most significant GO terms were genes involved in the endomembrane system, nucleotide binding and kinase activity. Our data revealed that there are a large number of microRNAs deregulated in PBMCs taken from patients with Klinefelter syndrome, of which certain novel and known microRNAs may be involved in the pathological process of Klinefelter syndrome. Further studies are necessary to determine the roles of microRNAs in the pathological process of Klinefelter syndrome in the future.

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood-brain barrier (BBB), resulting in the poor therapeutic outcomes.

Oxidative stress is an important cause of dopaminergic (DA) neuron apoptosis in Parkinson's disease (PD). Mesenchymal stromal cells (MSCs) possess antioxidative features. In this study, we investigated whether MSCs could reduce oxidative stress and protect DA neurons from apoptosis by intravenous (I.V.) injection in the early stage of a 6-hydroxydopamine (6-OHDA)-induced PD model. MSCs were injected into the tail vein of mice, and behavioral tests, immunofluorescence staining, western blot, and oxidative stress levels were assessed at different time points. After 6-OHDA exposure, DA neuron apoptosis was detected, together with severe oxidative stress in brain and periphery. Compared with the non-transplanted sham controls, motor function in the 6-OHDA-lesioned group after I.V. injection of MSCs was significantly improved, and the levels of DA neuron apoptosis and oxidative stress decreased. The results demonstrate that MSCs can rescue DA neurons from ongoing apoptosis by reducing oxidative stress, and provide insights on developing new therapeutic strategies to offset the degenerative process of PD.

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor, and the HER2 receptor; it is highly proliferative and becomes the deadliest forms of breast cancer. Effective prognostic methods and therapeutic targets for TNBC are required to improve patient outcomes. Here, we report that acidic nuclear phosphoprotein 32 family member E (ANP32E), which promotes cell proliferation in mammalian development, is highly expressed in TNBC cells compared to other types of breast cancer. High expression of ANP32E correlates significantly with worse overall survival (OS; P < 0.001) and higher risks of disease recurrence (P < 0.001) in patients with TNBC. Univariate and multivariate Cox-regression models show that ANP32E is an independent prognostic factor in TNBC. Furthermore, we discovered that ANP32E promotes tumor proliferation in vitro by inducing G1/S transition, and ANP32E inhibition suppresses tumor formation in vivo. By examining the expression of E2F1, cyclin E1, and cyclin E2, we discovered that ANP32E promotes the G1/S transition by transcriptionally inducing E2F1. Taken together, our study shows that ANP32E is an efficient prognostic marker, and it promotes the G1/S transition and induces tumorigenesis of TNBC cells by transcriptionally inducing E2F1.

Ovarian cancer is the most lethal cancer in the female reproductive system. It has been shown that 'time chemotherapy' of ovarian cancer has an important impact on the chemotherapy effect and prognosis of patients, but the specific mechanism is not known.

Lymph node metastasis (LNM) is a critical cause for disease progression and treatment failure in cervical cancer. However, the mechanism underlying cervical cancer LNM remains unclear. In this study, HN1 was found to be dramatically upregulated in cervical cancer and patients with higher HN1 expression are more likely to exhibit a higher rate of LNM and lower survival rate. Univariate and multivariate Cox-regression analyses showed that HN1 is an independent prognostic factor in cervical cancer. Meanwhile, HN1 promotes lymphangiogenesis of cervical cancer in vitro. The in vivo experiment also indicates that HN1 enhances LNM in cervical cancer. Furthermore, we also found that HN1 activated the NF-κB signaling pathway to enhance the expression of downstream genes. Taken together, our study suggests that HN1 plays a crucial role in promoting LNM and acts as a prognostic biomarker in cervical cancer.

Induced neural stem cells (iNSCs) can be reprogrammed from somatic cells and have shown potentials in treatment of various neurological diseases/disorders. Obtaining iNSCs of nonhuman primates serves as an important bridge for clinical translation using iNSCs. In the current study, cynomolgus (Macaca fascicularis) bone marrow mesenchymal stromal cells (MSCs) were reprogrammed into iNSCs by transduction of non-integrative Sendai virus encoding transgenes OCT4, SOX2, KLF4 and C-MYC. The obtained iNSCs showed characteristics of normal neural stem cells (NSCs) and could differentiate into neurons, astrocytes and oligodendrocytes. Furthermore, iNSCs could give rise to dopaminergic neural cells in vitro, which showed safety and efficacy after transplantation into the striatum of an immunodeficient mouse Parkinson's disease (PD) model.

Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies that is closely associated with the Hepatitis B virus (HBV). HBV integration into host genomes can induce instability and the aberrant expression of human genomic DNA. To directly assess HBV integration breakpoints at whole genome level, four small sequencing libraries were constructed and the HBV integration profiles of four patients with HCC were characterized. In total, the current study identified 11,800,974, 11,216,998, 11,026,546 and 11,607,842 clean reads for patients 1-3 and 4, respectively, of which 92.82, 95.95, 97.21 and 97.29% were properly aligned to the hybrid reference genome. In addition, 220 HBV integration events were detected from the tumor tissues of four patients with HCC and an average of 55 breakpoints per sample was calculated. The results indicated that HBV integration events may be implicated in HCC physiologies and diseases. The results acquired may also provide insight into the pathogenesis of HCC, which may be valuable for future HCC therapy.

HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear.

Despite advances in the treatment of cervical cancer (CC), the prognosis of patients with CC remains to be improved. This study aimed to explore candidate gene targets for CC. CC datasets were downloaded from the Gene Expression Omnibus database. Genes with similar expression trends in varying steps of CC development were clustered using Short Time-series Expression Miner (STEM) software. Gene functions were then analyzed using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein interactions among genes of interest were predicted, followed by drug-target genes and prognosis-associated genes. The expressions of the predicted genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Red and green profiles with upward and downward gene expressions, respectively, were screened using STEM software. Genes with increased expression were significantly enriched in DNA replication, cell-cycle-related biological processes, and the p53 signaling pathway. Based on the predicted results of the Drug-Gene Interaction database, 17 drug-gene interaction pairs, including 3 red profile genes (TOP2A, RRM2, and POLA1) and 16 drugs, were obtained. The Cancer Genome Atlas data analysis showed that high POLA1 expression was significantly correlated with prolonged survival, indicating that POLA1 is protective against CC. RT-qPCR and Western blotting showed that the expressions of TOP2A, RRM2, and POLA1 gradually increased in the multistep process of CC. TOP2A, RRM2, and POLA1 may be targets for the treatment of CC. However, many studies are needed to validate our findings.