Spindle apparatus coiled-coil protein 1 (SPDL1) serves as a novel prognostic biomarker in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified. METHODS: Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC. RESULTS: In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis. CONCLUSIONS: SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.

The role of lysosomes in cancer development and progression.

Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.

Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN-amplified neuroblastoma growth.

MYCN-amplified neuroblastoma (NB) is characterized by poor prognosis, and directly targeting MYCN has proven challenging. Here, we showed that aldehyde dehydrogenase family 18 member A1 (ALDH18A1) exerts profound impacts on the proliferation, self-renewal, and tumorigenicity of NB cells and is a potential risk factor in patients with NB, especially those with MYCN amplification. Mechanistic studies revealed that ALDH18A1 could both transcriptionally and posttranscriptionally regulate MYCN expression, with MYCN reciprocally transactivating ALDH18A1 and thus forming a positive feedback loop. Using molecular docking and screening, we identified an ALDH18A1-specific inhibitor, YG1702, and demonstrated that pharmacological inhibition of ALDH18A1 was sufficient to induce a less proliferative phenotype and confer tumor regression and prolonged survival in NB xenograft models, providing therapeutic insights into the disruption of this reciprocal regulatory loop in MYCN-amplified NB.

Systematic comparison of biologically active foreign ions-codoped calcium phosphate microparticles on osteogenic differentiation in rat osteoporotic and normal mesenchymal stem cells.

Osteoporosis is a disease characterized by structural deterioration of bone tissue, leading to skeletal fragility with increased fracture risk. Calcium phosphates (CaPs) are widely used in bone tissue engineering strategies as they have similarities to bone apatite except for the absence of trace elements (TEs) in the CaPs. Bioactive glasses (BGs) have also been used successfully in clinic for craniomaxillofacial and dental applications during the last two decades due to their excellent potential for bonding with bone and inducing osteoblastic differentiation. In this study, we evaluated the osteogenic effects of the ionic dissolution products of the quaternary Si-Sr-Zn-Mg-codoped CaP (TEs-CaP) or 45S5 Bioglass® (45S5 BG), both as mixtures and separately, on rat bone marrow-derived mesenchymal stem cells (rOMSCs & rMSCs) from osteoporotic and normal animals, using an MTT test and Alizarin Red S staining. The materials enhanced cell proliferation and osteogenic differentiation, especially the combination of the BG and TEs-CaP. Analysis by quantitative PCR and ELISA indicated that the expression of osteogenic-specific genes and proteins were elevated. These investigations suggest that the TEs-CaP and 45S5 BG operate synergistically to create an extracellular environment that promotes proliferation and terminal osteogenic differentiation of both osteoporotic and normal rMSCs.

[Effects of simulated nitrogen deposition on competition of weedy species (Echinochloa crusgalli var. mitis L.) and upland rice (Oryza sativa L.) under different air temperatures].

A greenhouse experiment was conducted to study the effects of simulated nitrogen deposition on the growth and competition of C4 weedy species (Echinochloa crusgalli var. mitis L. ) and C3 upland rice (Oryza sativa L.) under day/night temperature of 35 degrees C/25 degrees C and 30 degrees C/20 degrees C. The results showed that under day/night temperature 35 degrees C/25 degrees C, 4.0 g x m(-2) x a(-1) N deposition enhanced the shoot biomass of E. crusgalli and O. sativa by 29.18% and 27.80%, respectively, compared with control. The N and P uptake by E. crusgalli increased by 87.33% and 49.73%, respectively, but no change was found for O. sativa. Under 30 degrees C/20 degrees C, three N depositions (2, 4 and 6 g x m(-1) x a(-1) ) enhanced the shoot biomass, tiller number, and shoot N and P uptake of E. crusgalli by 48.99%, 72.68% and 36.18%, 111.11%, 122.22% and 144.44%, 108.88%, 129.22% and 134.29%, and 16.53%, 65.05% and 22.47%, respectively, but no changes were observed for O. sativa. Nitrogen deposition significantly increased the shoot biomass ratio of E. crusgalli to O. sativa under 30 degrees C/20 degrees C, but had no impact on this ratio under 35 degrees C/25 degrees C. It was suggested that N deposition could enhance the competition of E. crusgalli over O. sativa, especially under lower air temperature.

[Effect of flavonoids from Hippophae rhamniodes residues on blood lipoid metabolism and antioxidative activity in climacteric rats].

OBJECTIVE: To study the effect of flavonoids from seed residues of Hippophae rhamnoides (FH) on the lipid metabolism and antioxidative activity in climacteric rats. METHOD: Menopausal rats with aging were used in this experiment. The rats were fed with FH by gastrogavage for 13 weeks. The effect of drug on the lipid metabolism and the antioxidative activity were observed after the rats were killed. RESULT: Serum total cholesterol was decreased significantly in rats fed with FH, T-AOC and SOD in serum and liver were significantly higher than those in rats fed with water, and at the same time MDA was lower than that in rats fed with water. CONCLUSION: FH can improve the climacteric rats' lipid metabolism, and enhance the antioxidation in climacteric rats.