Uncovering the Localization and Function of a Novel Read-Through Transcript 'TOMM40-APOE'.

Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, TOMM40-APOE. With cDNA amplification from THP-1 cells, the TOMM40-APOE3 product was successfully generated. We also generated TOMM40-APOE4, another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability.

Acupuncture Can Regulate the Distribution of Lymphocyte Subsets and the Levels of Inflammatory Cytokines in Patients With Mild to Moderate Vascular Dementia.

Background: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease, but there is a lack of definitive treatment for VD. Acupuncture treatment is effective in improving the cognitive impairment and behavioral capacity of patients with VD. In recent years, more studies indicated that peripheral inflammation and abnormal peripheral immune function may aggravate neuroinflammation and cognitive dysfunction. However, there are few studies about the acupuncture and the abnormal peripheral immune function of VD. Also, few studies concern the regulating effect of acupuncture on peripheral immunity of patients with VD. Objective: The aim of this study was to explore the effect of the "sanjiao" acupuncture method on peripheral immunity of patients with mild to moderate VD. Methods: A total of 30 patients with VD were involved in the acupuncture group (AG), which was treated with the "sanjiao" acupuncture method once a day for six times a week and lasted for 12 weeks, and 30 healthy elderly people were assigned to the normal group (NG), which had no treatment. The distribution of lymphocyte subsets and the levels of some inflammatory cytokines in the peripheral blood of subjects were evaluated using the flow cytometry (FCM) and the enzyme-linked immunosorbent assay (ELISA). Results: A total of 60 subjects were involved in this study, while 58 subjects completed the entire trial. Before treatment, the levels of CD3+ T, CD4+ T cells, CD4+/CD8+, Tregs, B cells, IFN-γ, and IL-10 in patients with VD were significantly decreased compared with the normal group (all P < 0.05 or P < 0.01). The level of TNF-α in peripheral blood of patients with VD was significantly increased (P < 0.01). After acupuncture treatment, the levels of CD3+ T, CD4+ T cells, and IFN-γ were significantly increased (all P < 0.05 or P < 0.01). The level of TNF-α was significantly decreased (P < 0.01). The proportion of Tregs was increased (P < 0.01), but it was still lower than that of the normal group (P < 0.05). Conclusion: The acupuncture method can increase the proportion of CD3+, CD4+ T cells, and Tregs in peripheral blood of patients with VD. And, it reduces the levels of pro-inflammatory factor TNF-α, which achieves the anti-inflammatory effects and immunostimulation. It suggests that acupuncture can improve the peripheral immune dysfunction of patients with VD by regulating the distribution of lymphocyte subsets and the levels of inflammatory cytokines. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR-IOR-17012052].

Acupuncture promotes expression of Hsp84/86 and delays brain ageing in SAMP8 mice.

OBJECTIVE: To study the effects of acupuncture on expression of heat shock protein (Hsp) 84 and 86, and brain ageing, in the senescence accelerated mouse prone 8 (SAMP8) model of Alzheimer's disease. METHODS: 7-month-old male senescence resistant mouse strain 1 (SAMR1) and SAMP8 mice were assigned to the following groups, with 15 animals in each group: SAMR1 control (Rc), SAMP8 control (Pc), SAMP8 acupuncture (Pa), SAMP8 sham-acupuncture (Psa). The Pa group was given acupuncture treatment once daily for 15 days. Neuromuscular coordination and cognitive function of the mice were evaluated by the tightrope test and Morris water maze test, respectively. The number of neurons in the CA1, CA3 and dentate gyrus (DG) regions of the hippocampus were measured. The levels of oxidative stress and protein carbonyl, mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus were detected. RESULTS: Compared with the Rc group, in the Pc mice there was a lower success rate for the tightrope test, impaired cognitive abilities, a decline in neuron numbers, reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increased levels of superoxide anion and protein carbonyl, and decreased mRNA and protein levels of Hsp84 and Hsp86 (all P<0.05). After acupuncture treatment, the success rate for the tightrope test was elevated, cognitive function was improved, neuron numbers were enhanced, levels of SOD and GSH-Px were increased, levels of superoxide anion and protein carbonyl were decreased, and Hsp84 and Hsp86 mRNA and protein expression were increased in the Pa mice when compared with the Pc and Psa groups (all P<0.05). CONCLUSION: Acupuncture may delay brain ageing in SAMP8 mice by reducing oxidative protein damage and promoting Hsp84 and Hsp86 expression.

Effect of electro-scalp acupuncture on acute ischemic stroke: a randomized, single blind, trial.

OBJECTIVE: To determine the clinical efficacy and safety of electro-scalp acupuncture in the treatment of patients with acute ischemic stroke. METHODS: Totally 74 patients with acute ischemic stroke were enrolled and divided into either body acupuncture (Control) or electro-scalp acupuncture (ESA) groups according to randomized controlled principle. The patients in the control group were given body acupuncture treatment once daily for 28 d, whereas except for the body acupuncture, electro-scalp acupuncture was additional treatment given to the ESA group. Neurological deficits, everyday motor function and muscle strength were evaluated at baseline and the 28th d by NIH Stroke Scale (NIHSS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index Score (MBI), respectively. RESULTS: There were not obvious between-group differences in the baseline efficacy parameters (NIHSS, FMA and MBI) (all P > 0.05), whereas significant between-group differences were found in post-treatment NIHSS, FMA-UE and MBI scores (all P < 0.05). After acupuncture treatment, systematic within-group improvements were found in the two groups for any of the efficacy parameters assessed (all P < 0.01), and the ESA group showed higher significant improvements in NIHSS, FMA-UE and MBI scores (all P < 0.05). CONCLUSION: Electro-scalp acupuncture was efficacious in the treatment of acute ischemic stroke, which resulted in meaningful improvements in neurologic function, motor function and activities of daily living of patients.