Oral microbiome characteristics in patients with pediatric solid tumor.

Background: Pediatric solid tumor, the abnormal proliferation of solid tissues in children resulting in the formation of tumors, represent a prevailing malignant ailment among the younger population. Extensive literature highlights the inseparable association linking oral microbiome and adult tumors, but due to differences in age of onset, characteristics of onset, etc., there are many differences between Pediatric solid tumors and adult tumors, and therefore, studying the relationship between Pediatric solid tumor and the oral microbiota is also essential. Methods: To unravel the distinct characteristics of the oral microbiota within Pediatric solid tumor patients, 43 saliva samples, encompassing 23 Pediatric solid tumor patients and 20 healthy controls, were diligently procured. A meticulous screening process ensued, and conducted microbial MiSeq sequencing after screening. Results: We documented the oral microbiome attributes among pediatric diagnosed with solid tumors (PST), and meanwhile, we observed a significant trend of decreased oral microbiota diversity in the pediatric solid tumor group. There were notable disparities in microbial communities observed between the two groups, 18 genera including Veillonellaceae, Firmicutes unclassified, Coriobacteriia, Atopobiaceae, Negativicutes, were significantly enriched in PST patients, while 29 genera, including Gammaproteobacteria, Proteobacteria, Burkholderiales, Neisseriaceae, were dominant in the HCs group. It was found that PST group had 16 gene functions, including Amino acid metabolism, Cysteine and methionine metabolism, Photosynthesis antenna proteins, Arginine and proline metabolism, and Aminoacyl tRNA biosynthesi, were significantly dominant, while 29 gene functions that prevailed in HCs. Conclusion: This study characterized the oral microbiota of Pediatric solid tumor patients for the first time, and importantly, targeted biomarkers of oral microbiota may serve as powerful and non-invasive diagnostic tools for pediatric solid tumor patients.

Constrained Output-Feedback Control for Discrete-Time Fuzzy Systems With Local Nonlinear Models Subject to State and Input Constraints.

This article presents a new approach to design static output-feedback (SOF) controllers for constrained Takagi-Sugeno fuzzy systems with nonlinear consequents. The proposed SOF fuzzy control framework is established via the absolute stability theory with appropriate sector-bounded properties of the local state and input nonlinearities. Moreover, both state and input constraints are explicitly taken into account in the control design using set-invariance arguments. Especially, we include the local sector-bounded nonlinearities of the fuzzy systems in the construction of both the nonlinear controller and the nonquadratic Lyapunov function. Within the considered local control context, the new class of nonquadratic Lyapunov functions provides an effective solution to estimate the closed-loop domain of attraction, which can be nonconvex and even disconnected. The convexification procedure is performed using specific congruence transformations in accordance with the special structures of the proposed SOF controllers and nonquadratic Lyapunov functions. Consequently, the fuzzy SOF control design can be reformulated as an optimization problem under strict linear matrix inequality constraints with a linear search parameter. Compared to existing fuzzy SOF control schemes, the new structures of the control law and the Lyapunov function are more general and offer additional degrees of freedom for the control design. Both theoretical arguments and numerical illustrations are provided to demonstrate the effectiveness of the proposed approach in reducing the design conservatism.

ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and the therapeutic outcomes remain undesirable. Increasing evidence shows that aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) plays crucial roles in tumorigenesis of multiple tumors. However, the expression status and functions of ARNTL2 in PDAC remain elusive. Here we showed that ARNTL2 expression was markedly upregulated in PDAC tissues and cell lines. elevated expression of ARNTL2 was positively related to unfavorable prognosis. Knockdown of ARNTL2 could suppress motility and invasive ability of PDAC cells in vitro, as well as tumor development in vivo. In addition, microRNA-26a-5p (miR-26a-5p) was identified as the crucial specific arbitrator for ARNTL2 expression and the expression of miR-26a-5p was inversely correlated with ARNTL2 expression in PDAC tissues. Functionally, elevated expression of miR-26a-5p was found to inhibit the proliferation, migration, and invasion of PDAC cells in vitro, while ARNTL2 increased expression could partially abolish the suppressive effect of miR-26a-5p. Mechanism study indicated that elevated expression of miR-26a-5p suppressed TGF/BETA signaling pathway by targeting ARNTL2 in PDAC cells. In conclusion, our data suggested that ARNTL2 acted as an oncogene to regulate PDAC growth. MiR-26a-5p/ARNTL2 axis may be a novel therapeutic candidate target in PDAC treatment.

The Long Non-coding RNA ZFAS1 Sponges miR-193a-3p to Modulate Hepatoblastoma Growth by Targeting RALY via HGF/c-Met Pathway.

Hepatoblastoma (HB) is the most common and aggressive malignant hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Recently, long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) has been reported to be an oncogenic gene in multiple cancers. However, the expression status and specific role of ZFAS1 involved in cancer progression of human HB remain unknown. This study aimed to identify the role of ZFAS1/miR-193a-3p/RALY axis in the development of HB. Here we showed that the expression of ZFAS1 was significantly upregulated in both HB tissues and cell lines. High ZFAS1 expression was significantly associated with aggressive tumor phenotypes and poorer overall survival in HB. In vitro and in vivo function assays indicated that silencing of ZFAS1 significantly suppressed HB cell proliferation and invasion. Furthermore, miR-193a-3p was identified to be the target of ZFAS1. Subsequently, RALY was confirmed to be regulated by miR-193a-3p/ZFAS1 axis. Mechanistically, our results indicated that the ZFAS1 participated to the progression of HB via regulating the HGF/c-Met signaling. Collectively, these data demonstrated that ZFAS1 acted as an oncogene to promote initiation and progression of HB by regulating miR-193a-3p/RALY (RALY Heterogeneous Nuclear Ribonucleoprotein) axis via HGF/c-Met Pathway, which provides an efficient marker and new therapeutic target for HB.

LncRNA RMRP silence curbs neonatal neuroblastoma progression by regulating microRNA-206/tachykinin-1 receptor axis via inactivating extracellular signal-regulated kinases.

BACKGROUND: Neuroblastoma is the commonest malignancy in neonates. Long non-coding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to be an oncogenic factor in some malignancies. However, its roles and molecular mechanisms in neuroblastoma progression are poor defined. METHODS: The expression of RMRP, microRNA-206 (miR-206), and tachykinin-1 receptor (TACR1) mRNA was measured by RT-qPCR assay. Protein levels of TACR1, phosphorylated extracellular signal-regulated kinases (ERK) 1/2 (p-ERK1/2) and ERK1/2 were detected by western blot assay. Cell proliferation was assessed by CCK-8 and colony formation assays. Cell migratory and invasive capacities were determined using Transwell migration and invasion assays. The interaction between miR-206 and RMRP or TACR1 was verified by luciferase assay. The roles and molecular mechanisms of RMRP knockdown on the growth of neuroblastoma xenografts were examined in vivo. RESULTS: RMRP was highly expressed in neuroblastoma tissues. RMRP knockdown inhibited proliferation, migration and invasion in neuroblastoma cells. Moreover, TACR1 was a target of miR-206 and RMRP performed as a molecular sponge of miR-206 to sequester miR-206 from TACR1 in neuroblastoma cells. TACR1 overexpression abrogated the inhibitory effect of RMRP downregulation on neuroblastoma cell progression by activating ERK1/2 pathway. Inhibition of TACR1 and ERK1/2 pathway abated RMRP-mediated pro-proliferation effect in neuroblastoma cells. RMRP knockdown hindered neuroblastoma xenograft growth by regulating miR-206/TACR1 axis via inactivating ERK1/2 pathway in vivo. CONCLUSION: RMRP knockdown hindered the tumorigenesis and progression of neuroblastoma by regulating miR-206/TACR1 axis via inactivating ERK1/2 pathway, hinting a potential therapeutic target for neuroblastoma.