Development of Polymethine Dyes for NIR-II Fluorescence Imaging and Therapy.

Fluorescence imaging in the second near-infrared window (NIR-II) is burgeoning because of its higher imaging fidelity in monitoring physiological and pathological processes than clinical visible/the second near-infrared window fluorescence imaging. Notably, the imaging fidelity is heavily dependent on fluorescence agents. So far, indocyanine green, one of the polymethine dyes, with good biocompatibility and renal clearance is the only dye approved by the Food and Drug Administration, but it shows relatively low NIR-II brightness. Importantly, tremendous efforts are devoted to synthesizing polymethine dyes for imaging preclinically and clinically. They have shown feasibility in the customization of structure and properties to fulfill various needs in imaging and therapy. Herein, a timely update on NIR-II polymethine dyes, with a special focus on molecular design strategies for fluorescent, photoacoustic, and multimodal imaging, is offered. Furthermore, the progress of polymethine dyes in sensing pathological biomarkers and even reporting drug release is illustrated. Moreover, the NIR-II fluorescence imaging-guided therapies with polymethine dyes are summarized regarding chemo-, photothermal, photodynamic, and multimodal approaches. In addition, artificial intelligence is pointed out for its potential to expedite dye development. This comprehensive review will inspire interest among a wide audience and offer a handbook for people with an interest in NIR-II polymethine dyes.

[Retracted] Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R.

Following the publication of the above paper, a concerned reader drew to the Editors' attention that certain of the western blot data shown in Figs. 4B and 6D, and the scratch­wound assay data shown in Fig. 2D, were strikingly similar to data that had already appeared in previously published papers written by different authors at different institutes. Furthermore, there appeared to be anomalies associated with the cell invasion assay data portrayed in Fig. 2E. Having considered the issues identified, the Editor of Oncology Reports has decided that this article should be retracted from the Journal on account of the reappearance of previously published data and the uncertainties regarding the data in Fig. 2E. After consulting the authors, they agreed with the Editor's decision that this paper should be retracted. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1671­1679, 2016; DOI: 10.3892/or.2015.4498].

Potential Use of Anti-Cancer Drugs for Treatment of Preeclampsia by Targeting the miRNA-IGF1R-PI3K-AKT Axis.

Aim: Preeclampsia (PE) belongs to hypertensive disorders of pregnancy (HDP), which can cause maternal death worldwide. This study aimed to identify the miRNA-mRNA-associated ceRNA network and to find new treatment schedules for PE. Methods: 4 microarray datasets were downloaded from the Gene Expression Omnibus database. We obtained 1737 differentially expressed mRNAs (865 upregulated and 872 downregulated) and 148 differentially expressed miRNAs (76 upregulated and 72 downregulated) from the placenta tissues of PE, respectively. Functional enrichment analyses of DEmRNAs were performed. The regulatory relationship between DEmiRNAs and DEmRNA was predicted via related databases. An miRNA-mRNA regulatory network was constructed. Results: hsa-let-7c and IGF1R were identified as potential regulators for PE, and function enrichment analysis showed that the PI3K-Akt signaling pathway was closely related. Therefore, ceRNAs might regulate the PI3K-Akt signaling pathway via the upregulation of IGF1R by binding to hsa-let-7c, affecting invasion of trophoblast, angiogenesis, and proinflammation in PE. Further study demonstrated that anticancer drugs including the PI3K inhibitor, AKT inhibitor, and IGF-1 inhibitor might be a potential solution for PE treatment. Conclusions: The hsa-let-7c/IGF1R axis might affect the PI3K-Akt signaling pathway which is involved in the pathogenesis of PE, and inhibitors targeting this pathway might be used for PE treatment.

Determination of metabolic phenotype and potential biomarkers in the liver of heroin addicted mice with hepatotoxicity.

BACKGROUND: Heroin is a semi-synthetic opioid that is commonly abused drugs in the world. It can cause hepatic injury and lead to multiple organs dysfunction to its addicts. Only a few reports exist on the metabolic changes and mechanisms in the liver of heroin-addicted mice with hepatic injury. METHODS: Twelve adult male Kunming mice (30-40 g) were divided into two groups randomly. The mice in the heroin-addicted group were injected subcutaneously in the first ten days with an increased dosage of heroin from 10 mg/kg to 55 mg/kg. The dosage was then stabilized at 55 mg/kg for three days. The control group was injected with the same amount of saline in the same manner. The hepatic injury was confirmed through the combination of histopathological observation and aminotransferase (AST) and alanine aminotransferase (ALT) determination. The withdrawal symptoms were recorded and used for assessment of heroin addiction. Eventually, liver metabolic biomarkers of heroin-addicted mice with hepatotoxicity were measured using UHPLC-MS/MS. RESULTS: Biochemical analysis and histopathological observation showed that heroin-addicted mice had a liver injury. The liver metabolites of heroin-addicted mice changed significantly. Metabonomics analysis revealed 41 metabolites in the liver of addicted heroin mice as biomarkers involving 34 metabolic pathways. Among them, glutathione metabolism, taurine and hypotaurine metabolism, vitamin B2 metabolism, riboflavin metabolism, and single-carbon metabolism pathways were markedly dispruted. CONCLUSIONS: Heroin damages the liver and disrupts the liver's metabolic pathways. Glutathione, taurine, riboflavin, 4-pyridoxate, folic acid, and methionine are important metabolic biomarkers, which may be key targets of heroin-induced liver damage. Thus, this study provides an in-depth understanding of the mechanisms of heroin-induced hepatotoxicity and potential biomarkers of liver damage.

[Genetic analysis of 100 fetuses with cleft lip with or without palate].

OBJECTIVE: To explore the genetic basis for fetuses with cleft lip and palate. METHODS: For 100 fetuses diagnosed with cleft lip with or without palate, G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out on chorionic villi, amniotic fluid or cordocentesis samples. RESULTS: No genomic abnormality was found among 49 fetuses with isolated cleft lip and palate, while 12 genomic aberrations were found among 51 fetuses with syndromic cleft lip and palate, which included 4 cases with trisomy 13, 2 cases with trisomy 18, 1 with X chromosome aneuploidy, 2 with other chromosomal aneuploidies and 3 with pathogenic CNVs. CONCLUSION: The incidence of genomic abnormalities in fetuses with cleft lip and palate was high. In addition to chromosomal abnormalities, attention should also be paid to pathogenic CNVs.

Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R.

Accumulating evidence shows that microRNA-217 (miR-217) is frequently dysregulated in various cancers, and plays crucial roles in tumorigenesis and metastasis; however, the role and underlying molecular mechanism of miR-217 in human epithelial ovarian cancer (EOC) remains unclear. Here, we report that miR-217 expression was downregulated in EOC tissue and inversely correlated with advanced FIGO stage, high histological grading and lymph node metastasis (P<0.01). Function analysis revealed that the ectopic expression of miR-217 in EOC cells inhibited cell proliferation, migration and invasion in vitro, as well as suppressed tumor growth in vivo. Bioinformatics analysis and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF1R) as a direct target of miR-217 in EOC cells. Western blot assay showed that overexpression of miR-217 in EOC cells inhibited IGF1R expression. In addition, downregulation of IGF1R mimicked the tumor-suppressive effects of miR-217 in EOC cells, whereas the reintroduction of IGF1R partially abrogated the suppression effect induced by miR-217 on EOC cells. Collectively, these results demonstrated that miR-217 plays a tumor suppressor role in human epithelial ovarian cancer by directly targeting IGF1R gene, suggesting a new potential therapeutic target in EOC.

An orthodontic technique for minimally invasive extraction of impacted lower third molar.

PURPOSE: To present a novel orthodontic approach for minimally invasive extraction of impacted mandibular third molars (M3s) close to the inferior alveolar nerve (IAN). PATIENTS AND METHODS: Eight patients (8 M3s) requiring extraction of M3s were included in this study; there were 2 cases of horizontal impaction, 4 of mesioangular impaction, and 2 of vertical impaction. Cone-beam computed tomogram showed that the roots of impacted M3s in 2 cases interrupted the cortices of the mandibular canal, and those in the other 6 cases were very close to the IAN. Orthodontic treatment was performed in this study. The crowns of 5 impacted teeth were surgically exposed before the application of the orthodontic device, whereas bonding was performed directly to the occlusal surface of the other 3 M3s, which had partially erupted. The opposing maxillary M3s were removed in 3 cases. One-step orthodontic extraction was applied to vertically impacted M3s and 2-step treatment was applied to horizontally or mesioangularly impacted M3s. Success was defined as the separation of the impacted tooth from the IAN as visualized on cone-beam computed tomogram. RESULTS: After orthodontic treatment, all impacted M3s were extruded and separated from the IAN (mean, 6.6 months; range, 4 to 10 months), without any neurologic consequences. The average time of extraction was 5 minutes. In all 8 cases, new bone formation occurred distal to the adjacent second molar. CONCLUSION: This orthodontic technique may be a minimally invasive approach for the extraction of impacted M3s adjacent to the IAN, with a decreased risk of paresthesias and with osteoperiodontal advantages.