Patients with Parkinson's disease (PD) were often observed with gastrointestinal symptoms, which preceded the onset of motor symptoms. Neuropathology of PD has also been found in the enteric nervous system (ENS). Many studies have reported significant PD-related alterations of gut microbiota. This meta-analysis was performed to evaluate the differences of gut microbiota between patients with PD and healthy controls (HCs) across different geographical regions. We conducted a systematic online search for case-control studies detecting gut microbiota in patients with PD and HCs. Mean difference (MD) and 95% confidence interval (CI) were calculated to access alterations in the abundance of certain microbiota families in PD. Fifteen case-control studies were included in this meta-analysis study. Our results showed significant lower abundance levels of Prevotellaceae (MD = −0.37, 95% CI = −0.62 to −0.11), Faecalibacterium (MD = −0.41, 95% CI: −0.57 to −0.24), and Lachnospiraceae (MD = −0.34, 95% CI = −0.59 to −0.09) in patients with PD compared to HCs. Significant higher abundance level of Bifidobacteriaceae (MD = 0.38, 95%; CI = 0.12 to 0.63), Ruminococcaceae (MD = 0.58, 95% CI = 0.07 to 1.10), Verrucomicrobiaceae (MD = 0.45, 95% CI = 0.21 to 0.69), and Christensenellaceae (MD = 0.20, 95% CI = 0.07 to 0.34) was also found in patients with PD. Thus, shared alterations of certain gut microbiota were detected in patients with PD across different geographical regions. These PD-related gut microbiota dysbiosis might lead to the impairment of short-chain fatty acids (SCFAs) producing process, lipid metabolism, immunoregulatory function, and intestinal permeability, which contribute to the pathogenesis of PD.

Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn’t affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.

Activated T regulatory (T reg ) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T reg cells and the progression of human colon cancer. We designed a cross-sectional study of CD4 1 Foxp3 1 T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of T reg cells with colon cancer stage. The phenotypes, cytokine-release patterns and suppression ability of these T reg cells were analyzed. We found that T reg cells increased significantly in both peripheral blood and cancer tissue. In addition, the T reg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T reg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T reg cells (Foxp3 hi CD45RA 2 ) and nonsuppressive T reg cells (Foxp3 lo CD45RA 2 ), but not resting T reg cells (Foxp3 low CD45RA 1 ), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T reg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T-cell antigen-4. Activated T reg cells, however, secreted significantly lower levels of effector cytokines (interleukin-2, tumor necrosis factor-a and interferon-c) than did resting T reg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T reg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T reg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.CD4 þ Foxp3 þ Regulatory T cells (T reg cells) are essential to maintain self-tolerance and immune hemostasis. 1,2 They play important roles in a variety of human diseases including autoimmune disease, chronic infection and cancers. 3-5 A large body of evidence suggests that T reg cells are one of the major players for tumor immune suppression and the main obstacle to successful tumor immunotherapy. 3,[6][7][8] The prevalence of T reg cells significantly increases in the human peripheral blood and/or tumors of multiple types of cancers. 9-12 These cells are recruited to tumor sites, where they suppress antitumor cytotoxic responses. 3,[13][14][15] Animal models show that inhibiting T reg cells improves tumor immunity or enhances tumor vaccine therapeutic effects. 16,17 In human colon cancer, studies have revealed that CD4 þ CD25 þ Foxp3 þ T reg cells are increased in peripheral blood mononuclear cells (PBMCs) and draining lymph nodes. These T reg cells were capable of suppression on antigen-specific CD4 þ T cells. Surgical removal of colon cancer reduces the T reg cell population and restores antigen-specific CD4 þ activity. 18,19 However, it is believed that nonspecific suppression of T reg cells might be dangerous, as it may produce an overwhelming autoimmune response.Human CD4 þ Foxp3 þ T reg ce...