miR-335 Restrains the Aggressive Phenotypes of Ovarian Cancer Cells by Inhibiting COL11A1.

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPß/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

Neurotensin-Conjugated Reduced Graphene Oxide with Multi-Stage Near-Infrared-Triggered Synergic Targeted Neuron Gene Transfection In Vitro and In Vivo for Neurodegenerative Disease Therapy.

Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro-specific peptide)-conjugated polyethylenimine (PEI)-modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two-stage near-infrared (NIR)-laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First-stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second-stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO-PEI-NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC-12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi-stage stimuli-responsive NIR laser treatment. The combination of neuro-specific targeting peptide and external NIR-laser-triggered aid provides a nanoplatform for gene therapy in CNS diseases.

Surfactant-free, lipo-polymersomes stabilized by iron oxide nanoparticles/polymer interlayer for synergistically targeted and magnetically guided gene delivery.

Gene therapy holds promise to suppress carcinomas but still remains far removed from clinic because of the lack of a safe and effective delivery system. Besides enhancing transfection efficiency, the difficulty in gene therapy is how to deliver sufficient gene molecules to the site of interest. Herein, the rational design of surfactant-free lipo-polymersomes (LPPs) to overcome these problems is reported, simultaneously using a lipid-stabilized double emulsion approach. The LPPs are designed to conceal the cationic lipids and plasmid DNA inside the core along with iron oxide nanoparticles/polymer interlayer and a relatively neutral lipid shell to avoid the undesired interaction during circulation, leading to high accumulation in the tumors of mice. Furthermore, guided by an external magnetic field and the folic acid (FA) that target tumors via folate receptor-mediated endocytosis on the cell surface, the vectors demonstrate a 30-40-fold increase in cell uptake. Moreover, this synergistic tumor-targeted approach can enhance a 10-fold increase in in vivo transfection efficacy by promoting the delivery of LPPs to cancer cells and facilitating the endosomal escape of gene molecules. The new insights and capabilities represent a major step in nanovector engineering for safe and efficient gene delivery.

Uterine choriocarcinoma accompanied by an extremely high human chorionic gonadotropin level and thyrotoxicosis.

The conventional treatments given to a 24-year-old woman with metastatic uterine choriocarcinoma and clinical and biochemical thyrotoxicosis did not appear to have any effect, probably due to an extremely high serum human chorionic gonadotropin (hCG) level which was up to 11,910,000 mIU/mL, and were initially underscored in light of the 'high-dose hook effect'. To our knowledge, no extremely high hCG level in a uterine choriocarcinoma patient has been reported in the literature. Her decapacitating symptoms subsided after the first course of chemotherapy by etoposide, methotrexate, and actinomycin D-cyclophosphamide and vincristine (EMA-CO) regimen. The serum hCG level, which reflects the quantification of host tumor burden, returned to the reference range after the fifth course of chemotherapy and the thyroid function reached euthyroid status before the third course of chemotherapy; two final courses were administered after the hCG level became undetectable. Two years after remission of disease, the patient experienced a normal pregnancy, and a term baby girl was delivered vaginally. No recurrence of uterine choriocarcinoma has been noted for 7 years.

Prenatal diagnosis of alobar holoprosencephaly with cystic hygroma.

OBJECTIVE: Holoprosencephaly is a kind of brain anomaly characterized by inadequate cleavage of the prosencephalon during early embryogenesis. In addition, holoprosencephaly associated with cystic hygroma and hydrops fetalis has never been reported. In this article, we report a rare case of holoprosencephaly associated with cystic hygroma and hydrops fetalis diagnosed prenatally. CASE REPORT: A 28-year-old woman, gravida 2, para 0, artificial abortion 1, was referred to our antenatal clinic at 16 weeks of gestation due to fetal cystic hygroma detected by prenatal routine ultrasonography at a local hospital. In our clinic, single ventricle with fused thalami and cystic mass at the fetal neck as well as hydrops fetalis were noted by level II ultrasound. Under the impression of holoprosencephaly with cystic hygroma and hydrops fetalis, termination of pregnancy with misoprostol was undertaken. The histopathology of fetal autopsy confirmed our diagnosis and disclosed additional intracranial abnormalities. CONCLUSION: Fetus with holoprosencephaly might have other associated structural abnormalities. Cystic hygroma and hydrops fetalis are rare associations. Meticulous sonographic examination to depict the associated defects are necessary in any fetus with holoprosencephaly.

Acute viral hepatitis C-induced jaundice in pregnancy.

OBJECTIVE: Acute viral hepatitis C-induced jaundice in pregnancy is very rare and may be fatal. Here, we report a complicated case with acute hepatitis C-induced jaundice in pregnancy with successful management. CASE REPORT: A 27-year-old pregnant woman, gravida 2, para 1, with gestational age of 36 weeks and 5 days, was referred to our hospital due to jaundice and elevated liver enzymes of undetermined cause. She had been suffering from general weakness, diarrhea and vomiting for 1 week, and jaundice with tea-colored urine for 3 days. At our medical center, acute viral hepatitis C-induced jaundice was suspected. Since her general condition deteriorated at 36 weeks and 6 days of gestation, we decided to induce labor. A male baby was born smoothly via the vaginal route, with birth weight 2,857 g, birth length 48.6 cm, and 1- and 5-minute Apgar scores of 7 and 9, respectively. Maternal condition improved dramatically after delivery and her serum liver enzymes and bilirubin levels gradually approached normal ranges. CONCLUSION: Mothers and fetuses with acute viral hepatitis C-induced jaundice during pregnancy are at great risk of mortality and morbidity. Timely termination may be one of the choices of treatment when fetal maturity has been reached and the maternal condition has deteriorated.