Highlights d Knockdown of Ptbp1 converts Mu ¨ller glia into retinal ganglion cells in mature retinas d Central projections of converted retinal ganglion cells restore visual responses d Induction of neurons with dopaminergic features in PD model mice

Mast cell-derived chymase is implicated in myocardial fibrosis (MF), but the underlying mechanism of intracellular signaling remains unclear. Transforming growth factor-beta 1 (TGF-beta1) is identified as the most important profibrotic cytokine, and Smad proteins are essential, but not exclusive downstream components of TGF-beta 1 signaling. Moreover, novel evidence indicates that there is a cross talk between Smad and mitogen-activated protein kinase (MAPK) signaling cascade. We investigated whether chymase activated TGF-beta 1/Smad pathway and its potential role in MF by evaluating cardiac fibroblasts (CFs) proliferation and collagen synthesis in neonatal rats. MTT assay and 3H-Proline incorporation revealed that chymase induced CFs proliferation and collagen synthesis in a dose-dependent manner. RT-PCR and Western blot assay demonstrated that chymase not only increased TGF-beta1 expression but also upregulated phosphorylated-Smad2/3 protein. Furthermore, pretreatment with TGF-beta 1 neutralizing antibody suppressed chymase-induced cell growth, collagen production, and Smad activation. In contrast, the blockade of angiotensin II receptor had no effects on chymase-induced production of TGF-beta 1 and profibrotic action. Additionally, the inhibition of MAPK signaling had no effect on Smad activation elicited by chymase. These results suggest that chymase can promote CFs proliferation and collagen synthesis via TGF-beta 1/Smad pathway rather than angiotensin II, which is implicated in the process of MF.

Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson’s disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to the development of PD, and whether the change of HIP2 in blood could reflect its expression in the brain or motor functions in PD patients. In this study, we established a mouse line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to spontaneous motor function impairment and dopaminergic neuronal loss. Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6-hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons. Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model for PD, we observed concurrent, highly correlated decrease of HIP2 expression in the brain and in the blood. Using blood samples from more than 300 patients, we validated the decreased HIP2 mRNA in PD patients, including de novo patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2 mRNA levels accompanying improved motor and overall daily functions in 75% of the PD patients with instructed Tai Chi training. Therefore, our in vivo studies have indicated HIP2 insufficiency as a contributing factor for PD, and functionally validated blood HIP2 as a useful and reversible biomarker for PD.

I ntimai tear in ascending aorta usually develops following aortic pathology, such as aortic dissection and aortic pseudoaneurysm after thoracic surgery. [1][2][3][4] Open aortic replacement is the conventionally gold standard for ascending aortic pathology.In this report, we describe our initial experience with a novel minimally invasive device repair (MIDR) for intimal tear in ascending aorta in high-risk patients under transesophageal echocardiographic (TEE) guidance. METHODS Patient's Clinical DetailsBetween January 2017 and January 2021, 10 selected patients with intimal tear in ascending aorta were selected for MIDR. Clinical data was summarized in Table 1. The clinical protocol was approved by the Ethics Committee of the hospital and all patients provided informed written consent.