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Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. Methods: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and mitochondrial biogenesis related genes was measured by real-time polymerase chain reaction or Western blot analysis. Results: CTGF decreased OCR, ECAR, adenosine triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression in SAS cells. Conclusion: CTGF can decrease glycolysis, mitochondrial oxidative phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA protein degradation through ubiquitin proteasome pathway and in turn reduces migration and invasion of OSCC cells. Therefore, CTGF may be developed as a potential additive therapeutic drug for oral cancer in the near future.

We investigated the application of head-up tilt table testing (HUT) and management of neurocardiogenic syncope (NCS) in children, as pediatric studies are limited. Methods: Seventy-nine patients (ages 6-18 years) underwent HUT for evaluation of syncope. Patient triggers and premonitory symptoms allowed the clinical diagnosis of NCS or non-NCS. Results were divided into four hemodynamic types (1, 2A, 2B, and 3) according to patient response to HUT. Results: NCS occurred in 65 patients and non-NCS in 14 patients. Isoproterenol infusion significantly increased the sensitivity of the test (from 28% to 45%) and was associated with a slight decrease in the specificity (from 93% to 86%). Subjects in the type 1 group accounted for the majority of responses to the test (69%). There were no complications associated with the test. At follow-up (16.6 ± 9.3 months), the overall recurrence rate was 30.8% but NCS was less severe in most patients. The recurrence rate was similar for patients with a positive or negative HUT and for both pharmacologically and non-pharmacologically treated patients. Conclusion: HUT can be safely performed with a high specificity in children, with the sensitivity of HUT improved by isoproterenol. Therefore, a positive response to treatment is reassuring to the physician and family. NCS is generally a self-limited condition despite a high recurrence rate.