Though neurotransmitters are essential elements in neuronal signal transduction, techniques for in vivo analysis are still limited. Here, we describe an organic electrochemical transistor array (OECT-array) technique for monitoring catecholamine neurotransmitters (CA-NTs) in rat brains. The OECT-array is an active sensor with intrinsic amplification capability, allowing real-time and direct readout of transient CA-NT release with a sensitivity of nanomolar range and a temporal resolution of several milliseconds. The device has a working voltage lower than half of that typically used in a prevalent cyclic voltammetry measurement, and operates continuously in vivo for hours without significant signal drift, which is inaccessible for existing methods. With the OECT-array, we demonstrate simultaneous mapping of evoked dopamine release at multiple striatal brain regions in different physiological scenarios, and reveal a complex cross-talk between the mesolimbic and the nigrostriatal pathways, which is heterogeneously affected by the reciprocal innervation between ventral tegmental area and substantia nigra pars compacta.
Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G1 phase, which may be a result of poly(ADP-ribose) polymerase cleavage and caspase activation. Furthermore, 3,28-di-(2-nitroxy-acetyl)-oxy-BT-induced apoptosis was mitochondrion-mediated. The results of the present study demonstrated that Bcl-2-associated X protein translocated to the mitochondria from the cytosol following 3,28-di-(2-nitroxy-acetyl)-oxy-BT treatment. Notably, the phosphoinositide 3-kinase/protein kinase B signaling pathway was involved in 3,28-di-(2-nitroxy-acetyl)-oxy-BT-treated Huh7 cells. Therefore, the results of the present study demonstrated that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may inhibit HCC, which may be a possible application to treat HCC.
Background Upper limb and hand motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS), and the clinical efficacy of rehabilitation needs to be improved. This study aims to combine Jin’s three-needle acupuncture (JTN) therapy with mirror therapy (MT) for hemiplegia after CIS, objectively evaluate the clinical effects and safety of JTN to treat upper limb dysfunction, and use functional magnetic resonance imaging (fMRI) of the brain to investigate the central mechanisms of the effects, which would provide a powerful evidence-based medical basis for further supporting the application of JTN combined with MT. Methods/design This trial will be a single-blind, randomized controlled study. Patients who meet the study criteria will be recruited and randomly assigned to either the combined treatment group (JTN+MT) or the JTN group. Both interventions will be conducted for 6 days per week and last for 4 weeks. The primary outcome will be the effective rate based on the Fugl–Meyer Assessment for Upper Extremity (FMA-UE). Other outcome measures will include scores on the motor assessment scale (MAS), action research arm test (ARAT), activities of daily living (ADL) scale, and fMRI analyses. For safety evaluation, adverse events will be observed and recorded. Discussion This study may help to identify the efficacy and safety of acupuncture combined with MT for upper limb dysfunction after CIS and explore the central mechanisms with brain fMRI. Trial registration Chinese Clinical Trial Registry ChiCTR-IOR-17012174. Registered on 5 April 2017.
BackgroundThe purpose of this study was to systematically evaluate the effectiveness of acupuncture combined with balloon dilatation in patients with post-stroke cricopharyngeal achalasia (CPA) according to the effective rate, videofluoroscopy swallowing study (VFSS) score and standardized swallowing function assessment scale (SSA) score through Meta-analysis.MethodsEnglish and Chinese language literature published before July 24,2022 were searched in ten electronic databases. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. Using RevMan 5.4.1 software to perform Meta-analysis.Results10 studies with 517 patients with post-stroke CPA were included. Meta-analysis showed that the effective rate of the experience group was higher than that of the control group [OR = 0.62; 95% CI (2.32, 13.05); I2 = 0%; p = 0.0001]. Compared to the control group, the SSA score was lower in the experience group [MD = −4.22; 95% CI (−4.57, −3.87); I2 = 42%; p < 0.00001]. In terms of VFSS scores, the experience group showed greater efficacy differences than control group [MD = 1.53; 95% CI (1.32, 1.75); I2 = 0%; p < 0.00001]. The subgroup analysis of VFSS score based on the average course of disease (<1 month vs. ≥1 month) showed no significant difference. The subgroup analysis based on average age (>60 years vs. ≤60 years) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup older than 60 years. The subgroup analysis based on the treatment course (>30 days vs. ≤30 days) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup the treatment course>30 days.ConclusionAcupuncture combined with balloon dilatation may be an effective method for treating post-stroke CPA. Compared with balloon dilatation, acupuncture combined with balloon can significantly improve the swallowing function of patients, and it is also effective for patients of different courses, ages, and treatment course, while patients over 60 years old and the treatment course over 30 days may have better clinical outcomes.
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