Cancer multimodal treatment by combining the effects of different theranostics agents can efficiently improve treatment efficacy and reduce side effects. In this work, we demonstrate the theranostics nanodevices on the basis of Cu-loaded polydopamine nanoparticles (CuPDA NPs), which are able to offer magnetic resonance imaging (MRI)-guided thermochemotherapy (TCT). Systematical studies reveal that after Cu ions loading, the molar extinction coefficient of PDA NPs is greatly enhanced by 4 times, thus improving the performance in photothermal therapy. Despite Cu ions being toxic, the release of Cu is mainly stimulated in acidic environment. Once the NPs deposit in the slightly acidic tumor microenvironment (pH ≈ 6.5-6.8), the release rate boosts ∼30%, which effectively avoids the systematic toxicity during chemotherapy. Meanwhile, due to the increment of the electron-proton dipole-dipole interaction correlation time τ, the spin-lattice relaxation time (T) for PDA NPs is found to be shortened by Cu loading, which boosts the longitudinal relaxivity (r). Hence, CuPDA NPs can be used as T-weighted contrast agent in MRI. In addition, due to the naturally existing DA in the human body with stealth effect, CuPDA NPs have an outstanding tumor retention rate as high as 8.2% ID/g. Further in vitro and in vivo tests indicate that CuPDA NPs possess long blood circulation time, good photothermal and physiological stability, and biocompatibility, which are potential nanodevices for MRI-guided TCT with minimal side effects.

Iron oxide (Fe3O4), polydopamine (PDA), and in particular their composites are examples of the safest nanomaterials for developing multifunctional nanodevices to perform noninvasive tumor diagnosis and therapy. However, the structures and performances of Fe3O4-PDA nanocomposites should be further perfected to enhance the theranostic efficiency. In this work, we demonstrate the fabrication of PDA-capped Fe3O4 (Fe3O4@PDA) superparticles (SPs) employing preassembled Fe3O4 nanoparticles (NPs) as the cores. Owing to the collective effect of preassembled Fe3O4 NPs, the superparamagnetism and photothermal performance of Fe3O4@PDA SPs are greatly enhanced, thus producing nanodevices with improved magnetic resonance imaging (MRI)-guided photothermal efficiency. Systematical studies reveal that the molar extinction coefficient of the as-assembled Fe3O4 SPs is 3 orders of magnitude higher than that of individual Fe3O4 NPs. Also due to the high aggregation degree of Fe3O4 NPs, the T2-weighted MRI contrast is greatly enhanced for the SPs with r2 relaxivity of 230.5 mM(-1) s(-1), which is ∼2.5 times larger than that of individual Fe3O4 NPs. The photothermal stability, physiological stability, and biocompatibility, as well as the photothermal performance of Fe3O4 SPs, are further improved by enveloping with PDA shell.

SummaryTendon injuries are significant clinical problems. Current treatments often result in incomplete repair or healing, which may lead to reduced function and rupture. Stem cell-based therapy is a promising intervention for tendon repair. In this article, we attempt to provide a brief overview on the recent progress in the field, current understanding of the underlying mechanisms of the approach, and the potential of stem cell-based therapies beyond cell implantation. We conclude the review by sharing our viewpoints on the challenges, opportunities, and future directions of this approach.The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

Recent studies suggest that microRNAs (miRNAs) are critical regulators in many types of cancer, including osteosarcoma. miR-342-3p has emerged as an important cancer-related miRNA in several types of cancers. However, the functional significance of miR-342-3p in osteosarcoma is unknown. The aims of this study were to investigate whether miR-342-3p is dysregulated in osteosarcoma and to explore the biological function of miR-342-3p in regulating cellular processes of osteosarcoma cells. We found that miR-342-3p expression was significantly decreased in osteosarcoma tissues and cell lines. Overexpression of miR-342-3p inhibits the proliferation, migration, and invasion of osteosarcoma cells. In contrast, the inhibition of miR-342-3p exhibited the opposite effect. Astrocyte-elevated gene-1 (AEG-1) was identified as one of the target genes of miR-342-3p in osteosarcoma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Overexpression of miR-342-3p also inhibited the Wnt and nuclear factor κB signaling pathways. Moreover, overexpression of AEG-1 partially rescued the inhibitory effects of miR-342-3p mediated on the proliferation, migration, and invasion of osteosarcoma cells. Overall, our results show that miR-342-3p inhibits the proliferation, migration, and invasion of osteosarcoma cells through targeting AEG-1, suggesting a potential target for the development of miRNA-based therapy for osteosarcoma.

The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management.

Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found in the abdomen, but may occasionally present at uncommon sites including the cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely rare. In this report, we describe a 12-year-old girl with giant GN in the thoracic spine, who underwent successful resection (T1–4 level) of the tumor. Histopathological examination confirmed the diagnosis. GN should be considered in the differential diagnosis of any paraspinal mass. A high index of suspicion and correlation of clinico-radiological findings is necessary in differentiating a large benign tumor from a malignant growth. Complete surgical excision is the treatment of choice; however tumor size and location need to be considered for the surgical approach (one-step or multiple surgeries). Close follow-up after surgery is mandatory.

Osteosarcoma is the most bone-associated malignancy with high lethality. The current therapeutic strategy benefits little on the survival of patients. Studies have shown that aberrant activation of Wnt/β-catenin pathway is essential for the progression of osteosarcoma, implying that targeting this signaling may be an effective way of therapeutics. Recently, TIKI family has been identified as a new class of negative regulators for Wnt/β-catenin pathway. However, the implication of TIKIs with osteosarcoma has not been explored. Here, we constructed an adenoviral vector that expresses TIKI2 in osteosarcoma cells (Ad-TIKI2). TIKI2 expression was found to be reduced in osteosarcoma specimens and cell lines. In tested osteosarcoma cells, the activation of Wnt/β-catenin pathway was found to be inhibited by TIKI2 expression. Furthermore, the proliferation, colony formation ability, and invasion were all significantly suppressed in osteosarcoma cells infected with Ad-TIKI2. Finally, animal experiments further confirmed that TIKI2 restoration was able to inhibit the growth of osteosarcoma in vivo. Taken together, we provided evidence that reduced expression of TIKI family protein in osteosarcoma may participate in the progression of osteosarcoma and restoring its expression was able to impair the growth of osteosarcoma.

This study's goal is to determine similarities and differences in the molecular pathways or potential functions of the various targeted regions or genes of the Vegf family-VegfA, VegfB, VegfC, and Pgf-using the BXD genetic reference panel. Data from whole genome expression profiles of retinas from the well-characterized mouse recombinant inbred (RI) strain population derived from C57BL/6J X DBA/2J (BXD) were analyzed. Multiple analytical tools and statistical strategies were used to investigate the expression level. The expression Quantitative Trait Loci (QTLs) of these probes were mapped and compared. Our data showed that VegfA2 has the highest expression levels among all probes of Vegf genes. The expression levels of Vegf family genes are not significantly correlated. In the overall comparison, expression levels of VegfA1 and VegfA2 are positively correlated (R = 0.540). The expression levels of VegfB and VegfC are weakly correlated (R = 0.360). VegfC is also weakly correlated with the expression levels of Pgf (R = 0.324). The interaction of VegfB- and VegfA2-associated 50a2 genes was very weak (R50 ab = 0.3129). The interaction of top VegfB-associated 50b genes with VegfA2 has a reciprocal negative impact (R50ba = -0.42758). The VegfC-associated top 50c genes are strongly correlated with VegfB (R50 cb = 0.8159), while they are negatively correlated with VegfA2 (R50ca = -0.1450). Expression quantitative trait loci (eQTL) analysis suggested that the regulatory mechanisms for the expression levels of these genes in the Vegf family are different from each other. The expression level of VegfA associates with a group of genes that are not associated with other genes in the Vegf family.