The pathogenesis of CRC remains to be further understood. This study was designed to elucidate the role of Foxp3+IL-17+ T cells in the pathogenesis of CRC. Surgically removed CRC tissue was collected from 12 patients with CRC. The frequency and cytokine profile of Foxp3+IL-17+ T cells in CRC were examined by flow cytometry. Chemokine CXCL11 was examined in CRC tissue by Western blotting. Treg chemotaxis was examined in a transwell system. The effect of Foxp3+IL-17+ T cells on induction of cancer-initiating cells was examined; the latter's Akt and MAPK activities and colony formation were examined afterward. Abundant Foxp3+IL-17+ T cells were detected in CRC tissue that expresses high levels of TGF-β, CXCR3, CCR6, and RORγt. High levels of CXCL11 were detected in CRC tissue-derived CD68+ cells, which had a strong chemotactic effect on Foxp3+ Tregs. Hypoxia induced the expression of IL-17 in Foxp3+ Tregs; Foxp3+IL-17+ T cells were capable of inducing CRC-associated cell markers in BMMo and drove the cells to be cancer-initiating cells. High levels of phosphorylated Akt and MAPK were detected in the induced cancer-initiation cells; the latter has the capability to form a colony. CRC tissue-derived Foxp3+IL-17+ cells have the capacity to induce cancer-initiating cells.

Structural equation modeling (SEM) and fMRI were used to test whether changes in the regional activity are accompanied by changes in the inter-regional connectivity as motor practice progresses. Ten healthy subjects were trained to perform finger movement task daily for 4 weeks. Three sessions of fMRI images were acquired within four weeks. The changes in inter-regional connectivity were evaluated by measuring the effective connectivity between the primary motor area (M1), supplementary motor area (SMA), dorsal premotor cortex (PMd), basal ganglia (BG), cerebellum (CB), and posterior ventrolateral prefrontal cortex (pVLPFC). The regional activities in M1 and SMA increased from pre-training to Week 2 and decreased from Week 2 to Week 4. The inter-regional connectivity generally increased in strength (with SEM path coefficients becoming more positive or negative) as practice progressed. The increases in the strength of the inter-regional connectivity may reflect long-term reorganization of the skilled motor network. We suggest that the performance gain was achieved by dynamically tuning the inter-regional connectivity in the motor network.

Neuroimaging studies of functional activation often only reflect differentiated involvement of brain regions compared between task performance and control states. Signals common for both states are typically not revealed. Previous motor learning studies have shown that extensive motor skill training can induce profound changes in regional activity in both task and control states. To address the issue of brain activity changes in the resting-state, we explored long-term motor training induced neuronal and physiological changes in normal human subjects using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Ten healthy subjects performed a finger movement task daily for four weeks, during which three sessions of fMRI images and two sessions of PET images were acquired. Using a classical data analysis strategy, we found that the brain activation increased first and then returned to the pre-training, replicating previous findings. Interestingly, we also observed that motor skill training induced significant increases in regional cerebral blood flow (rCBF) in both task and resting states as the practice progressed. The apparent decrease in activation may actually result from a greater increase in activity in the resting state, rather than a decrease in the task state. By showing that training can affect the resting state, our findings have profound implications for the interpretation of functional activations in neuroimaging studies. Combining changes in resting state with activation data should greatly enhance our understanding of the mechanisms of motor-skill learning.

Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 ( FSCN1 ) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1 . Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1 . Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC.