Influence of acupuncture on cognitive function and markers of oxidative DNA damage in patients with vascular dementia

AbstractObjectiveTo test the influence of acupuncture on cognitive function and a marker of oxidative DNA damage in patients with vascular dementia (VD).MethodsSixteen VD patients were evaluated before and after acupuncture, using the Folstein Mini-Mental State Examination-Revised (MMSE-R) to assess cognitive function, and the ADL-R scale to assess independence in activities of daily living (ADL). Life quality was evaluated using the DEMQOL (Dementia quality of life questionnaire) questionnaire, and syndromes and expression of vascular dementia were evaluated with the Scale for the Differentiation of Syndromes of Vascular Dementia (SDSVD). In addition, the urine concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG) —a marker of oxidative damage—was quantified with enzyme-linked immunosorbent assay.ResultsThe MMSE-R and DEMQOL scores were higher after acupuncture than before (P<0.05), while there were no obvious differences in the ADL-R or SDSVD scores (P>0.05). The 8-OHdG content in urine significantly decreased after acupuncture (P<0.05).ConclusionAcupuncture reduces the levels of 8-OHdG and improves cognitive function and quality of life in VD patients, suggesting that acupuncture is beneficial at least in part by preventing oxidative damage

Fasudil in Combination With Bone Marrow Stromal Cells (BMSCs) Attenuates Alzheimer\u27s Disease-Related Changes Through the Regulation of the Peripheral Immune System.

Alzheimer\u27s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 1

Acupuncture Effect and Central Autonomic Regulation

Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects

Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer\u27s disease.

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer\u27s disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD-C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid-β1-42 (Aβ 1-42 ), Tau protein phosphorylation (P-tau) and β-site APP-cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD-C10 administration boosted the expression of synapse-associated proteins, such as postynaptic density protein 95, synaptophsin, α-amino 3-hydroxy-5-methyl-4-isoxa-zolep-propionate receptor and neurotrophic factors, e,g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Taken together, our results demonstrate that FSD-C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ 1-42 and P-tau, and promoting the generation of synapse-associated proteins and neurotrophic factors

Effects of sea-buckthorn leaves on performance and serum metabolic profiles in Altay lambs

In this study, the effects of sea-buckthorn (Hippophae rhamnoides L.) leaves (SL) on the biochemical parameters and metabolomic profiling in Altay lamb (Ovis aries) were observed. Sixty six-month-old male Altay lambs (body weight 28.0 ± 3.5 kg) were randomly assigned to four groups (n=15). The experimental groups were named as CON, 2.5%, 5.0% and 7.5%. The group CON, contained animals fed with a basal diet. Animals of the other groups were fed a treatment diet consisting of 2.5% (Group 2.5%), 5.0% (Group 5.0%) and 7.5% (Group 7.5%) SL. The experimental period lasted 56 days. The results showed that the average daily gain (ADG) and average daily feed intake (ADFI) increased with the increase in the levels of dietary SL. Dietary SL showed a direct relationship with total protein (TP), albumin, globulin and total cholesterol (TC) content of the experimental animals. However, an indirect relationship was observed between dietary SL and the concentration of urea nitrogen (UN). The concentrations of glucose, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) showed quadratic change. Additional changes occurred in the endogenous metabolites involving multiple pathways. The pathways were tricarboxylic acid (TCA) cycle, the metabolism of protein and amino acid and the metabolism of fatty acid and steroid. The changes in metabolites primarily revealed an increase in amino acids and carbohydrates and a decrease in lipid metabolites. These findings provide a comprehensive insight into the effects of the metabolic aspects of sea-buckthorn leaves on Altay lambs. In addition, the present research results provide a better understanding to the development and utilization of sea-buckthorn as a healthy additive for small ruminant production.Keywords: Hippophae rhamnoides L., lamb, metabolomics, growth performance, serum parameter

Acupuncture for Vascular Dementia: A Pragmatic Randomized Clinical Trial

In this trial, patients who agreed to random assignment were allocated to a randomized acupuncture group (R-acupuncture group) or control group. Those who declined randomization were assigned to a nonrandomized acupuncture group (NR-acupuncture group). Patients in the R-acupuncture group and NR-acupuncture group received up to 21 acupuncture sessions during a period of 6 weeks plus routine care, while the control group received routine care alone. Cognitive function, activities of daily living, and quality of life were assessed by mini-mental state examination (MMSE), Activities of Daily Living Scale (ADL), and dementia quality of life questionnaire (DEMQOL), respectively. All the data were collected at baseline, after 6-week treatment, and after 4-week follow-up. No significant differences of MMSE scores were observed among the three groups but pooled-acupuncture group had significant higher score than control group. Compared to control group, ADL score significantly decreased in NR-acupuncture group and pooled-acupuncture group. For DEMQOL scores, no significant differences were observed among the three groups, as well as between pooled-acupuncture group and control group. Additional acupuncture to routine care may have beneficial effects on the improvements of cognitive status and activities of daily living but have limited efficacy on health-related quality of life in VaD patients

Fasudil in Combination With Bone Marrow Stromal Cells (BMSCs) Attenuates Alzheimer’s Disease-Related Changes Through the Regulation of the Peripheral Immune System

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)- homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 106 BMSCs /time/mouse), Fasudil combined with BMSCs, or saline (i.p., control) for 2 months. Morris water maze (MWM) test was used to evaluate learning and memory. The mononuclear cells (MNCs) of spleens of APP/PS1 Tg mice were analyzed using flow cytometry for CD4+ T-cells, macrophages, and the pro-inflammatory and anti-inflammatory molecules of the macrophages. Immunohistochemical staining was used to examine the expression of ROCK-II in the spleens of APP/PS1 Tg mice. The MWM test showed improved spatial learning ability in APP/PS1 Tg mice treated with Fasudil or BMSCs alone or in combination, compared to untreated APP/PS1 Tg mice. Fasudil combined with BMSCs intervention significantly promoted the proliferation of CD4+/CD25+ and CD4+/ IL-10 lymphocytes, induced the release of cytokine factors, and regulated the balance of the immune system to work functionally. It also shifted M1 (MHC-II, CD86) to M2 (IL-10, CD206) phenotype of macrophages of CD11b and significantly enhanced the anti-inflammatory and phagocytic abilities (CD16/32) of macrophages of CD11b. Immunohistochemical staining showed significantly decreased expression of ROCK-II in mice treated with combination of Fasudil with BMSCs as compared to saline control. Fasudil in combination of BMSCs improved cognition of APP/PS1 Tg mice through the regulation of the peripheral immune system, including reduction of ROCK-II expression and increased proportion of anti-inflammatory M2 mononuclear phenotype and phagocytic macrophages in the spleen of the peripheral immune system. The latter was achieved through the communication between brain and spleen to improve the immunoregulation of CNS and AD disease conditions

FSD-C10: A more promising novel ROCK inhibitor than Fasudil for treatment of CNS autoimmunity.

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and vasodilation between Fasudil and FSD-C10. The results demonstrated that FSD-C10, like Fasudil, induced neurite outgrowth of neurons and dendritic formation of BV-2 microglia and enhanced the production of neurotrophic factor brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3). However, the cell cytotoxicity and vasodilation of FSD-C10 were relatively small compared with Fasudil. Although Fasudil inhibited both ROCK I and ROCK II, FSD-C10 more selectively suppressed ROCK II, but not ROCK I, which may be related to vasodilation insensitivity and animal mortality. Thus, FSD-C10 may be a safer and more promising novel ROCK inhibitor than Fasudil for the treatment of several neurological disorders