[Early electroacupuncture intervention delays progression of disease in mice with amyotrophic lateral sclerosis by down-regulating TLR4/NF-κB signaling].

OBJECTIVE: To observe the effect of early electroacupuncture (EA) intervention on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in mice with amyotrophic lateral sclerosis (ALS), so as to explore its mechanisms underlying alleviation of ALS. METHODS: Fifty-four ALS (ALS-SOD1G93A) mice with SOD1G93A gene mutation identified by PCR were randomly divided into model group, 60 day(d) EA group and 90 d EA group(n=18 mice in each group), and other 18 ALS-SOD1G93A negative mice were used as the control group. At the age of 60 and 90 days, mice of the two EA groups received EA (2 Hz, 1 mA) stimulation of bilateral "Jiaji" (EX-B2) of L1-L2 and L5-L6 for 20 min, twice a week for 4 weeks,respectively. When being 60 days old, the mice in the model and control groups were subjected to the same binding as that in the two EA groups but without EA intervention. The tail suspension test was used to judge the onset time of disease and the survival period, and rotary rod fatigue test was used to evaluate the hind limb motor function. Nissl staining method was used to observe the content of Nissl bodies in the anterior horn of the lumbar spinal cord. Immunohistochemical staining was used to observe the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in the anterior horn of the lumbar spinal cord, and Western blot was used to detect the relative expression of TLR4, NF-κB and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord. RESULTS: The disease onset time apparently delayed in the 60 d EA group than in the model group (P<0.01). The survival time was apparently shorter in the model group than in the control group (P<0.01), and obviously prolonged in the 60 d EA and 90 d EA groups than in the model group (P<0.01). The rotatory rod time was obviously shorter in the model group than in the control group (P<0.05), and apparently longer in the 60 d EA group than in the model group and 90 d EA group (P<0.05). Compared with the control group, the model group had a decrease in the number of Nissl bodies in the anterior horn of the lumbar spinal cord (P<0.01), and an increase in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.01). In contrast to the model group, both 60 d EA and 90 d EA groups had an apparent increase in the number of Nissl bodies and a marked decrease in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.05, P<0.01). The therapeutic effects of 60 d EA group were evidently superior to those of 90 d EA group in delaying the onset time of disease, prolonging the survival time and rotatory rod time, increasing the number of Nissl bodies, and in down-regulating the expression of Iba-1, TLR4, NF-κB and TNF-α (P<0.05, P<0.01). CONCLUSION: The early intervention of EX-B2 EA is more effective in delaying the progression of ALS than post-onset intervention in ALS-SOD1G93A mice, which may be related to its functions in inhibiting the excessive activation of microglia, and down-regulating TLR4/NF-κB signaling.

A Systematic Screening of Traditional Chinese Medicine Identifies Two Novel Inhibitors Against the Cytotoxic Aggregation of Amyloid Beta.

The toxic aggregates of amyloid beta (Aß) disrupt the cell membrane, induce oxidative stress and mitochondrial dysfunction, and eventually lead to Alzheimer's disease (AD). Intervening with this cytotoxic aggregation process has been suggested as a potential therapeutic approach for AD and other protein misfolding diseases. Traditional Chinese Medicine (TCM) has been used to treat AD and related cognitive impairment for centuries with obvious efficacy. Extracts or active ingredients of TCMs have been reported to inhibit the aggregation and cytotoxicity of Aß. However, there is a lack of systematic research on the anti-Aß aggregation effects of TCM components. In this study, we performed a systematic screening to identify the active ingredients of TCM against the cytotoxic aggregation of Aß42. Through a literature and database survey, we selected 19 TCM herbals frequently used in the treatment of AD, from which 76 major active chemicals without known anti-amyloid effects were further screened. This took place through two rounds of MTT-based screening detection of the cytotoxicity of these chemicals and their effects on Aß42-induced cytotoxicity, respectively. Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and sinapic acid (SA) were found to be less toxic, and they inhibited the cytotoxicity of Aß42. Further studies demonstrated that TSG and SA concentration-dependently attenuated the amyloidosis and membrane disruption ability of Aß42. Thus, we identified two novel chemicals (TSG and SA) against the cytotoxic aggregation of Aß42. Nonetheless, further exploration of their therapeutic potential is warranted.

[Tiaoshen acupuncture method combined with electroacupuncture for diarrhea-type irritable bowel syndrome : a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between Tiaoshen acupuncture method combined with electroacupuncture (EA) and EA alone in the treatment of diarrhea-type irritable bowel syndrome (IBS-D). METHODS: A total of 76 patients of IBS-D were randomly divided into a Tiaoshen group (38 cases, 2 cases dropped off ) and an EA group (38 cases, 1 case dropped off). The EA group was treated with acupuncture at Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25), Dachangshu (BL 25), Zusanli (ST 36), Shangjuxu (ST 37), etc. for 30 min. The bilateral Tianshu (ST 25) and the same side of Zusanli (ST 36) and Shangjuxu (ST 37) were connected EA (discontinuous wave, 1 Hz in frequency, 4-6 mA in current intensity). In the Tiaoshen group, the Tiaoshen acupuncture method was added on the basis of the EA group. The acupoints were Baihui (GV 20), Shenting (GV 24) and Benshen (GB 13), and the needles were retained for 30 min. Both groups were treated once a day, 6 days as a course of treatment, with an interval of 1 d between treatment courses, and a total of 4 courses of treatment were required. The IBS symptom severity scale (IBS-SSS) score, IBS quality of life scale (IBS-QOL) score and Hamilton depression scale (HAMD) score were observed before and after treatment in the two groups, and the clinical effect was evaluated. RESULTS: After treatment, the total effective rate in the Tiaoshen group was 94.4% (34/36), which was higher than 78.4% (29/37) in the EA group (P<0.05). The IBS-SSS and HAMD scores of both groups after treatment were lower than before treatment (P<0.05), while IBS-QOL scores were higher than before treatment (P<0.05). Moreover, the changes of above scores in the Tiaoshen group were higher than those in the EA group (P<0.05). CONCLUSION: The Tiaoshen acupuncture method combined with EA have a significant effect in treatment of IBS-D, can significantly reduce the symptoms of abdominal pain, abdominal distension and diarrhea in patients, effectively improve patients' quality of life and depression condition, the effect is better than the simple EA treatment.

Effects of Dietary Phospholipids on Growth Performance, Digestive Enzymes Activity and Intestinal Health of Largemouth Bass (Micropterus salmoides) Larvae.

While the beneficial roles of dietary phospholipids on health status and overall performances of fish larvae have been well demonstrated, the underlying mechanisms remain unclear. To address this gap, the present study was conducted to investigate the effects of dietary phospholipids on growth performance, intestinal development, immune response and microbiota of larval largemouth bass (Micropterus salmoides). Five isonitrogenous and isolipidic micro-diets were formulated to contain graded inclusion levels of phospholipids (1.69, 3.11, 5.23, 7.43 and 9.29%). Results showed that the supplementation of dietary phospholipids linearly improved the growth performance of largemouth bass larvae. The inclusion of dietary phospholipids increased the activity of digestive enzymes, such as lipase, trypsin and alkaline phosphatase, and promoted the expression of tight junction proteins including ZO-1, claudin-4 and claudin-5. Additionally, dietary phospholipids inclusion alleviated the accumulation of intestinal triacylglycerols, and further elevated the activity of lysozyme. Dietary phospholipids inhibited the transcription of some pro-inflammatory cytokines, including il-1ß, and tnf-α, but promoted the expression of anti-inflammatory cytokines tgf-ß, with these modifications being suggested to be mediated by the p38MAPK/Nf-κB pathway. The analysis of bacterial 16S rRNA V3-4 region indicated that the intestinal microbiota profile was significantly altered at the genus level with dietary phospholipids inclusion, including a decreased richness of pathogenic bacteria genera Klebsiella in larval intestine. In summary, it was showed that largemouth bass larvae have a specific requirement for dietary phospholipids, and this study provided novel insights on how dietary phospholipids supplementation contributes to improving the growth performance, digestive tract development and intestinal health.

Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature.

Gardner syndrome (GS) is an autosomal dominant disease characterized by the presence of colonic polyposis, osteoma and soft tissue tumors. It is regarded as a clinical subgroup of familial adenomatous polyposis (FAP) and may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 23-year-old female patient with GS who presented with gastric polyposis and was successively treated with restorative proctocolectomy in combination with ileal pouch anal anastomosis (RPC/ IPAA), ileostomy, ileostomy closure operation, snare polypectomy during 8 mo. After operation, the patient took oral traditional Chinese medicine pills made of Fructus mume and Bombyx batryticatu for about 6 mo. The innutrition and anaemia of this patient were gradually improved. Gastroscopy showed that the remnant gastric polypi gradually decreased and finally disappeared 19 mo after the first operation. The patient had 2-3 times of solid stool per day at the time we wrote this paper.