S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation.

Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks. During the last 4 weeks, SAM (16 mg/kg) was co-administrated with D-galactose. Behavior tests were used to assess cognitive function and depression-like behaviors of rats. Results showed that cognitive impairment and depression-like behaviors were reversed by SAM. SAM reduced neuronal cell loss, increased brain-derived neurotrophic factor level in the hippocampus, inhibited amyloid-ß level and microglia activation, as well as pro-inflammatory factors levels in the hippocampus and serum. Further, SAM enhanced antioxidant capacity and attenuated cholinergic damage by reducing malondialdehyde levels, increasing acetylcholine levels, expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the hippocampus. Above all, SAM has a potential neuroprotective effect on ameliorating cognitive impairment in brain aging, which is related to inhibition of oxidative stress and neuroinflammation, as well as α7nAChR signals. DATA AVAILABILITY: Data will be made available on request.

Research status, hotspots and trends of acupuncture and moxibustion in the treatment of Alzheimer's disease: A bibliometric analysis.

BACKGROUND: Acupuncture and moxibustion (AM) are utilized to treat Alzheimer's disease (AD). However, no bibliometric analysis has explored this issue. Thus, this study investigated the status, hotspots and trends of AM in the treatment of AD. METHODS: CiteSpace and VOSviewer softwares were used to analyze the literature on the AM for AD in the Web of Science Core Collection database. We analyzed the data of countries/regions, institutions, journals, authors, keywords, and cited references. RESULTS: After removing duplicates, 193 articles were retrieved. The number of publications on this topic has increased gradually. The most productive and collaborative country was China (143 documents), followed by South Korea (19). The top 3 active academic institutions were Beijing University of Chinese Medicine, Capital Medicine University, and Guangzhou University of Chinese Medicine. The most productive journal was Evidence-based Complementary and Alternative Medicine (13 documents), followed by the Frontiers in Aging Neuroscience (10), Medicine (10), and Neural Regeneration Research (10). The top 3 co-cited journals were Evidence-based Complementary and Alternative Medicine (156 citations), Acupuncture Electro-therapeutics Research (152), and Acupuncture in Medicine (146). The research hotspots in this domain are dementia, memory, hippocampus, mouse models, and Parkinson's disease. Major frontiers are comparing the therapeutic effects of acupuncture and donepezil and electroacupuncture at different frequencies in this field. CONCLUSION: This bibliometric study identified relevant hotspots and trends in research on AM in the treatment of AD, which can provide researchers with key information in this domain and help further explore new research directions.

Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats.

Baihui-penetrating-Qubin acupuncture is frequently used to treat intracerebral hemorrhage (ICH) in China. Acupuncture affects multiple microRNAs in diseases. MicroRNA-23a-3p (miR-23a-3p) has been demonstrated to be up-regulated in ICH patients. Herein, the effect of Baihui-penetrating-Qubin acupuncture on miR-23a-3p expression after ICH and the role of miR-23a-3p in ICH were discussed. A rat model of ICH was induced by infusing autologous blood into caudate nucleus. Acupuncture was performed after ICH once a day for 30 min. After 3 consecutive days of acupuncture, the neurobehavioral function, brain edema, neuronal cell death, inflammation, ferroptosis, nuclear factor E2-like 2 (NFE2L2) signaling and miR-23a-3p levels in brain tissues were analyzed. Additionally, antagomiR-23a-3p was injected into rats 3 days prior to ICH modeling to analyze the function of miR-23a-3p in neuronal cell death, inflammation, ferroptosis, and NFE2L2 signaling. Acupuncture relieved the ICH-induced neurological function deficits, increases in brain water content and Fluoro-Jade B (FJB)-positive cells and release of proinflammatory cytokines. Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. This study provides a potential mechanism underlying the Baihui-penetrating-Qubin acupuncture improving the early injury after ICH.

[Effect of electroacupuncture at governor vessel on learning-memory ability and serum level of APP, Aß1-42 in patients with Alzheimer's disease].

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism. METHODS: Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and ß-amyloid protein 1-42 (Aß1-42) were detected by ELISA. RESULTS: Compared before treatment, the MoCA scores were increased after treatment in the two groups (P<0.05), and the MoCA score in the observation group was higher than that in the control group (P<0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups (P<0.05), and the ADAS-Cog score in the observation group was lower than that in the control group (P<0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups (P<0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group (P<0.05). Compared before treatment, the serum levels of APP and Aß1-42 were lower after treatment in the two groups (P<0.05), and the serum levels of APP and Aß1-42 in the observation group were lower than those in the control group (P<0.05). CONCLUSION: EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aß1-42 and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.

Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats.

BACKGROUND: An increasing number of studies have shown that obesity is the key etiological agent of cardiovascular diseases, nonalcoholic fatty liver disease, type 2 diabetes and several kinds of cancer and that gut microbiota change was one of the reasons suffering from obesity. At present, the gut microbiota has gained increased attention as a potential energy metabolism organ. Our recent study reported that cordycepin, a major bioactive component separated from Cordyceps militaris, prevented body weight gain in mice fed a high-fat diet directly acting to adipocytes, however, the effect of cordycepin regulating gut microbiota keeps unknown. METHODS: In this research, we synthesized cordycepin (3-deoxyadenosine) by chemical methods and verified that cordycepin reduces body weight gain and fat accumulation around the epididymis and the kidneys of rats fed a high-fat diet. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to test the species of intestinal bacteria in high-fat-diet-induced obese rats. RESULTS: We found that cordycepin modifies the relative abundance of intestinal bacteria in high-fat-diet-induced obese rats. However, cordycepin did not alter the variety of bacteria in the intestine. Cordycepin treatment dramatically reversed the relative abundance of two dominant bacterial phyla (Bacteroidetes and Firmicutes) in the high-fat-diet-induced obese rats, resulting in abundance similar to that of the chow diet group. CONCLUSION: Our study suggests that cordycepin can reduce body weight and microbiome done by cordycepin seems be a result among its mechanisms of obesity reduction.

Vitamin D Deficiency Promotes Liver Tumor Growth in Transforming Growth Factor-ß/Smad3-Deficient Mice Through Wnt and Toll-like Receptor 7 Pathway Modulation.

Disruption of the TGF-ß pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-ß signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-ß pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-ß pathway member expression levels and ß-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-ß member expression with lower ß-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-ß pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and ß-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling.

IL-30 (IL27p28) attenuates liver fibrosis through inducing NKG2D-rae1 interaction between NKT and activated hepatic stellate cells in mice.

UNLABELLED: Chronic hepatic diseases, such as cirrhosis, hepatocellular carcinoma, and virus-mediated immunopathogenic infections, affect billions of people worldwide. These diseases commonly initiate with fibrosis. Owing to the various side effects of antifibrotic therapy and the difficulty of diagnosing asymptomatic patients, suitable medication remains a major concern. To overcome this drawback, the use of cytokine-based sustained therapy might be a suitable alternative with minimal side effects. Here, we studied the therapeutic efficacy and potential mechanisms of interleukin (IL)-30 as antifibrosis therapy in murine liver fibrosis models. CCl4 or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) 0.1% (wt/wt) Purina 5015 Chow (LabDiet, St. Louis, MO) was fed for 3 weeks to induce liver fibrosis. Either control vector (pCtr) or pIL30 was injected hydrodynamically once per week. A significant decrease in collagen deposition and reduced expression of alpha-smooth muscle actin (α-SMA) protein indicated that IL-30-based gene therapy dramatically reduced bridging fibrosis that was induced by CCl4 or DDC. Immunophenotyping and knockout studies showed that IL-30 recruits natural-killer-like T (NKT) cells to the liver to remove activated hepatic stellate cells (HSCs) significantly and ameliorate liver fibrosis. Both flow cytometric and antibody-mediated neutralization studies showed that liver NKT cells up-regulate the natural killer group 2, member D (NKG2D) ligand and bind with the NKG2D ligand, retinoic acid early inducible 1 (Rae1), and positively activated HSCs to ameliorate liver fibrosis. Furthermore, adoptive transfer of liver NKT cells in T-cell-deficient mice showed reduction of fibrosis upon IL-30 administration. CONCLUSIONS: Highly target-specific liver NKT cells selectively remove activated HSCs through an NKG2D-Rae1 interaction to ameliorate liver fibrosis after IL-30 treatment.