Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

GHRH expression plasmid improves osteoporosis and skin damage in aged mice.

The hormone secretion of GHRH-GH-IGF-1 axis in animals was decreased as aging. These hormones play an important role in maintaining bone mass and bone structure, and also affect the normal structure and function of the skin. We used plasmid-based technology to deliver growth hormone releasing hormone (GHRH) to elderly mice. In the current study, 80 and 120 µg/kg pVAX-GHRH plasmid expression plasmid were injected into old mice, the serum GHRH and insulin-like growth factor-1(IGF-1) content were increased within three weeks (P < 0.05). In the groups of 80 and 120 µg/kg plasmid, the content of procollagen type I N-terminal pro-peptide (PINP) in the serum was increased(P < 0.05), and the content of C-terminal telopeptides of type I collagen (CTX-1) in the serum was reduced significantly (P < 0.05). Furthermore, the expression of osteoprotegerin (OPG) and osteocalcin (OCN) in the femur also was increased(P < 0.05). The bone mineral density(BMD)、trabecular bone volume (BV/TV) and trabecular number(Tb.N) of mouse femur were increased significantly (P < 0.05) and trabecular separation(Tb.Sp) was decreased(P < 0.05). There were more trabecular bones in the bone marrow cavity and the trabecular bones are thicker in the groups of 80 and 120 µg/kg plasmid relative to control. The superoxide dismutase (SOD) content in the skin was increased(P < 0.05), and the malondialdehyde (MDA) content was reduced significantly (P < 0.05). Meanwhile, the skin moisture content also increased significantly(P < 0.05). Moreover, the expression of matrix metalloproteinase 3(MMP3) and matrix metalloproteinase 9(MMP9) was decreased in the skin(P < 0.05). The thickness of the dermis and epidermis of the skin had increased significantly(P < 0.05). Skin structure is more dense and complete in the two groups. These results indicate that 80 and 120 µg/kg plasmid-mediated GHRH supplementation can improve osteoporosis and skin aging in aged mice.

Effect of Moringa oleifera supplementation on productive performance, colostrum composition and serum biochemical indexes of sow.

Moringa oleifera has been considered as a potential functional feed or food, since it contains multiple components beneficial to animal and human. However, little is known about the effects of Moringa oleifera supplementation on productive performances in sows. In the current study, the results showed that dietary Moringa oleifera significantly decreased the farrowing length and the number of stillborn (p < .05), while had an increasing trend in the number of live-born (0.05 < p < .10). Furthermore, 8% Moringa oleifera supplementation significantly elevated protein levels in the colostrum (p < .05); 4% Moringa oleifera lowed serum urea nitrogen of sows after 90 days of gestation (p < .05) and significantly decreased serum glucose on 10 days of lactation (p < .05). Both groups showed significant elevation in serum T-AOC activity (p < .05). The serum malondialdehyde (MDA) of sows declined significantly in 4% Moringa oleifera addition group (p < .05). 8% Moringa oleifera meal significantly elevated serum CAT activity after 60 days of gestation (p < .05), while decreased the serum MDA level and increased the serum GSH-Px activity of sows at 10 days of lactation (p < .05). Of piglets, both two dosages of Moringa oleifera supplementation essentially reduced the serum urea nitrogen (p < .05), and 4% Moringa oleifera meal increased serum total protein (p < .05). In addition, piglets that received 8% Moringa oleifera had the highest serum CAT and SOD activities among all groups (p < .05). The present study indicated that Moringa oleifera supplementation could enhance the reproduction performances, elevate protein levels in the colostrum and improve the serum antioxidant indices in both sows and piglets.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

Exploration of long noncoding RNA in bovine milk exosomes and their stability during digestion in vitro.

Previous studies have demonstrated that bovine milk contains mRNA and microRNA that are largely encapsulated in milk-derived exosomes. However, little information is available about long noncoding RNAs (lncRNA) in bovine milk. Increasing evidence suggests that lncRNA are of particular interest given their key role in gene expression and development. We performed a comprehensive analysis of lncRNA in bovine milk exosomes by RNA sequencing. We used a validated human in vitro digestion model to investigate the stability of lncRNA encapsulated in bovine milk exosomes during the digestion process. We identified 3,475 novel lncRNA and 6 annotated lncRNA. The lncRNA shared characteristics with those of other mammals in terms of length, exon number, and open reading frames. However, lncRNA showed higher expression than mRNAs. We selected 12 lncRNA of high-expression abundance and identified them by PCR. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that lncRNA regulate immune function, osteoblastogenesis, neurodevelopment, reproduction, cell proliferation, and cell-cell communication. We also investigated the 12 lncRNA using quantitative real-time PCR to reveal their expression profiles in milk exosomes during different stages of lactation (colostrum 2 d, 30 d, 150 d, and 270 d); their resulting expression levels in milk exosomes showed variations across the stages. A digestion experiment showed that bovine milk exosome lncRNA was resistant to in vitro digestion with different digestive juices, including saliva, gastric juice, pancreatic juice, and bile juice. Taken together, these results show for the first time that cow milk contains lncRNA, and that their abundance varied at different stages of lactation. As expected, bovine milk exosomal lncRNA were stable during in vitro digestion. These findings provide a basis for further understanding of the physiological role of milk lncRNA.

Tian Wang Bu Xin Dan for Insomnia: A Systematic Review of Efficacy and Safety.

BACKGROUND: The Traditional Chinese Medicine (TCM) Tian Wang Bu Xin Dan (TWBXD) has been used widely for treating insomnia in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of TWBXD in the treatment of insomnia. OBJECTIVE: This study evaluated the efficacy and safety of TWBXD for insomnia. METHODS: We searched seven main databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wan-fang. We identified randomized-controlled trials (RCTs) for insomnia treatment involving TWBXD, TWBXD combined with conventional Western medicine, and conventional Western medicine from their inception to May 2018. The quality of literature was evaluated by Cochrane assessing tool to reduce the risk of bias. Meta-analysis and heterogeneity of results across the trials were performed. RevMan 5.3 was used to synthesize the results. RESULTS: 14 studies involving 1,256 participants were identified in this systematic review. Methodological deficiencies existed in most of the included trials. Few studies described the generation of a random sequence in detail, the concealment of allocation, and the methods of blinding. No placebo was used in treatment. 12 trials compared TWBXD with conventional Western medicine and 2 trials compared TWBXD combined with conventional Western medicine. The results of our meta-analysis showed relative benefits in effective rates in favor of TWBXD (Odds Ratio [OR] 2.71, 95% confidence interval [CI] 1.67 to 4.39, P < 0.00001) and TWBXD combined with conventional Western medicine (OR 5.05, 95% CI 1.58 to 16.12, P=0.006). The Pittsburgh Sleep Quality Index (PSQI) scores showed similar results, which favored TWBXD (Weighted Mean Difference [WMD] -1.82, 95% CI -3.00 to -0.64, P=0.003). Only 5 trials reported adverse events, whereas the other 9 trials did not provide the safety information. CONCLUSION: This review demonstrates that although the effects of TWBXD on insomnia were promising, they need to be interpreted with caution, due to the poor methodological quality and the small number of trials of the included studies. TWBXD seems to be generally safe, but there is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further studies on a larger scale with more rigorous designs are required to evaluate the role of TWBXD in the insomnia treatment.

Alterations of static functional connectivity and dynamic functional connectivity in motor execution regions after stroke.

The aims of this study were to examine both static functional connectivity (FC) and dynamic FC alterations in motor execution regions after stroke and to investigate whether the altered static or dynamic FC was associated with the clinical behaviors in stroke patients. Seventy-six stroke patients and 55 healthy controls (HC) were recruited. Static FC and dynamic FC maps were computed based on the seeds of six core regions in motor execution network. Correlation analyses were performed between static or dynamic FC and clinical behavioral scores in stroke patients. Compared with the HC, the stroke patients had significantly higher static FC between the seeds and the precentral or postcentral gyrus, frontal gyrus, inferior parietal lobule, thalamus and insula, and lower static FC between the seeds and the cerebellum and middle temporal gyrus. There were significant differences in dynamic FC between the seeds and precuneus, calcarine gyrus, insula, inferior parietal lobule, precentral gyrus, and middle temporal, frontal or occipital gyrus between the stroke patients and HC. Furthermore, a significant negative correlation was found between the Fugl-Meyer assessment scores and dynamic FC of the ipsilesional primary motor cortex and contralesional precentral gyrus in patients. The current study shows that the patterns of both static FC and dynamic FC changed after stroke, and correlation between motor function and temporal variability in the FC of the precentral gyrus was significant in stroke patients. Our findings indicate that dynamic FC might be a potential indicator for evaluating motor function after stroke.

Improvement of anti-nutritional effect resulting from ß-glucanase specific expression in the parotid gland of transgenic pigs.

ß-Glucan is the predominant anti-nutritional factors in monogastric animal feed. Although ß-glucanase supplementation in diet can help to eliminate the adverse effects, enzyme stability is substantially modified during the feed manufacturing process. To determine whether the expression of endogenous ß-glucanase gene (GLU) in vivo can improve digestibility of dietary ß-glucan and absorption of nutrients, we successfully produced transgenic pigs via nuclear transfer which express the GLU from Paenibacillus polymyxa CP7 in the parotid gland. In three live transgenic founders, ß-glucanase activities in the saliva were 3.2, 0.07 and 0.03 U/mL, respectively, and interestingly the enzyme activities increased in the pigs from 178 days old to 789 days old. From the feed the amount of gross energy, crude protein and crude fat absorbed by the transgenic pigs was significantly higher than the non-transgenic pigs. Meanwhile the moisture content of the feces was significantly reduced in transgenic pigs compared with the non-transgenic pigs. Furthermore, in all positive G1 pigs, ß-glucanase activity was detectable and the highest enzyme activity reached 3.5 U/mL in saliva. Also, crude protein digestion was significantly higher in G1 transgenic pigs than in control pigs. Taken together, our data showed that the transgenic ß-glucanase exerted its biological catalytic function in vivo in the saliva, and the improved performance of the transgenic pigs could be accurately passed on to the offspring, indicating a promising alternative approach to improving nutrient availability was established to improve utilization of livestock feed through transgenic animals.

Effect of ginseng polysaccharides on the immunity and growth of piglets by dietary supplementation during late pregnancy and lactating sows.

There are many reports that dietary supplementation with plant polysaccharides in pigs might promote their growth, but little is known about the maternal effect of ginseng polysaccharides (GPS) on piglets' growth by dietary supplementation to pregnant and lactating sows. In the current study, the effects of dietary supplementation with GPS on the immunity of sows and growth of their piglets were investigated. Results showed no significant difference among the four groups in the total number of piglets, live piglets, weak piglets and birth weight of piglets, indicating the GPS-treatment has no adverse effect on reproduction. Furthermore, the weaning weight of the GPS-treated groups was higher than that of control group (P < 0.05); among them, the addition of 200 mg/kg dose has the best effect. Interestingly, GPS increased the total immunoglobulin G concentration in milk and serum of sows (P < 0.05). The concentrations of interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and interferon-γ in milk and serum of sows were also increased in the experimental groups relative to the control (P < 0.05). Meanwhile, maternal supplementation of GPS significantly increased IL-2 and TNF-α concentration in the piglets' serum of the experimental groups relative to control (P < 0.05). GPS (200 mg/kg) significantly increased the glutathione peroxidase activity in milk and serum (P < 0.05), while the concentrations of malondialdehyde were significantly reduced (P < 0.05). The present results indicated that GPS supplementation during late pregnancy and lactation improved immunity-related bio-molecular levels in sow serum and milk, which may be further beneficial to piglet health and growth through biological transmission effects.

Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with Myasthenia Gravis: A Systematic Review and Meta-Analysis.

BACKGROUND: The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has been used widely for treating myasthenia gravis (MG) in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing therapy as an adjunctive therapy in MG patients. METHODS: Seven electronic databases were searched through June 2016. Randomized controlled trials (RCTs) evaluating the add-on effect of Qi-supplementing therapy in MG patients were included. The outcome measures were the total effective rate, relapse rate, and adverse events. RESULTS: Twenty-three RCTs involving 1,691 MG patients were included. The included studies were of low-to-moderate quality. Meta-analysis showed that Qi-supplementing therapy combined with Western medicine (WM) significantly improved the total response rate and reduced the relapse risk during 6-24 months of follow-up. Subgroup analysis showed that Qi-supplementing therapy only affected the total response rate within the first 6 months of treatment. Moreover, the rate of adverse events was lower with the addition of Qi-supplementing therapy to WM than with WM only. CONCLUSIONS: Short-term Qi-supplementing therapy combined with WM appears to be superior to WM for improving the total response rate and reducing the relapse rate. However, more high-quality RCTs are warranted owing to methodological flaws of previous trials.

The anorexigenic effect of serotonin is mediated by the generation of NADPH oxidase-dependent ROS.

Serotonin (5-HT) is a central inhibitor of food intake in mammals. Thus far, the intracellular mechanisms for the effect of serotonin on appetite regulation remain unclear. It has been recently demonstrated that reactive oxygen species (ROS) in the hypothalamus are a crucial integrative target for the regulation of food intake. To investigate the role of ROS in the serotonin-induced anorexigenic effects, conscious mice were treated with 5-HT alone or combination with Trolox (a ROS scavenger) or Apocynin (an NADPH oxidase inhibitor) by acute intracerebroventricular injection. Both Trolox and Apocynin reversed the anorexigenic action of 5-HT and the 5-HT-induced hypothalamic ROS elevation. The mRNA and protein expression levels of pro-opiomelanocortin (POMC) were dramatically increased after ICV injection with 5-HT. The anorexigenic action of 5-HT was accompanied by markedly elevated hypothalamic MDA levels and GSH-Px activity, while the SOD activity was decreased. Moreover, 5-HT significantly increased the mRNA expression of UCP-2 but reduced the levels of UCP-3. Both Trolox and Apocynin could block the 5-HT-induced changes in UCP-2 and UCP-3 gene expression. Our study demonstrates for the first time that the anorexigenic effect of 5-HT is mediated by the generation of ROS in the hypothalamus through an NADPH oxidase-dependent pathway.

The effect of dietary Panax ginseng polysaccharide extract on the immune responses in white shrimp, Litopenaeus vannamei.

The immunostimulatory effects of orally administered Panax ginseng root or its polysaccharides (GSP) in white shrimp, Litopenaeus vannamei, were investigated in this study. Shrimp were fed a diet containing 0.4 g kg⁻¹ GSP over a period of 84 days, during which the activities of total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), acid phosphatase (ACP), and alkaline phosphatase (AKP), as well as malondialdehyde (MDA) content, and expressions of cytosolic superoxide dismutase (cyt-SOD), CAT, GSH-Px, and peroxiredoxin (Prx) genes were determined in various tissues of the shrimp. Results showed that the shrimp fed the GSP diet had significantly increased ACP and AKP activities in the gills. The GSP-fed shrimp also displayed significantly increased T-SOD and GSH-Px activities in the gills and hepatopancreas of the shrimp; meanwhile there was enhanced CAT activity in the gills, but decreased MDA content in the gills, hepatopancreas and muscle. The mRNA expressions of cyt-SOD, CAT, GSH-Px and Prx were significantly elevated in the gills and hepatopancreas of the shrimp fed the GSP diet for 84 days, compared with that of the control. Therefore, GSP can be used as an immunostimulant for shrimp through dietary administration to increase immune enzyme activity and modify expression of immune genes in shrimp.

[Anxiety disease: decreased of functional connectivity in left superior temporal gyrus (GTs) and right GTs].

OBJECTIVE: Neuronal circuits involved in the pathophysiology of anxiety are not yet fully understood. We used functional connectivity MRI to explore the characteristic of functional connectivity in anxiety disorders patient and the neural mechanism of this disease. This work was selected as an oral presentation in 2006 ISMRM. METHODS: Twenty right-handed subjects were included in this study, and were divided into two groups. The anxiety (P) group (n = 10; 7 male, mean age 42 years) consisted of patients meeting DSM-IV criteria for a principal diagnosis of anxiety disorder. The control (C) group consisted of volunteers free of psychiatric symptoms, and was matched on age and gender (n = 10; 7 male) with the panic patients. The subjects underwent noninvasive functional magnetic resonance imaging while listening actively to (1): emotionally neutral word alternating with no word as the control condition (CN, PN), and (2): threat-related words alternating with emotionally neutral word as the experimental condition (CT, PT). Each word was presented in pseudorandom order in each 16 s block of 12 words of the same type. Eight alternating blocks of neutral words were presented for about 256 s. The subject was only asked to passively listen to each word. All MRI data were obtained on a 1.5-Tesla scanner Data analysis was performed with SPM99 to find significant activations in two tasks for two groups. Based on group t-test, we chose two anatomically defined regions: left superior temporal gyrus (GTs) and right GTs. Then, based on individual t-map, the voxel with the largest t-value within two regions was taken as the subject-specific peak voxel. We define clusters based on faces and edges, but not corners, so each voxel has 18 neighbors. Subject-specific averaged time series were extracted by averaging the time series of 19 voxels. Since healthy control subjects showed no significant activation (corrected, P < 0.05) during processing of anxiety word to neutral word, region of interest during processing of neutral word to no word was used as substitution. The connectivity degree eta(i j) between the node i and the node j is used to identify the change of the functional connectivity associated with differential tasks, which calculated by using the methods that have developed by ourselves. Moreover, we just consider coherence in low-frequency (0-0.15 Hz). RESULTS: The activation brain regions have been reported in our previous work. Patients were significant different from normal controls on two experiments. The connectivity degree of left Gts and right Gts in two tasks across all subjects was calculated. Comparing during processing neutral word to blank, a significant decrease (P < 0.001) in functional degree was observed during processing of threaten word to neutral word (eta = 0.5636 for CN, eta = 0.555 for CT, eta = 0.5616 for PN, eta = 0.4926 for PT). Especially, the greater decrease connectivity degree was identified for patient group compared with normal control during threat-related words alternating with emotionally neutral word condition. The connectivity degree identifies that functional interactions change with differential task. CONCLUSION: This result suggests decreased functional connectivity among left superior temporal gyrus and right GTs during processing of anxiety word to neutral word in anxiety patients. This dysfunction may mediate the neural mechanism of this sort of disease.

Randomized and controlled clinical study of modified prescriptions of Simiao Pill in the treatment of acute gouty arthritis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the compatibility of a modified prescription of Simiao Pill in the treatment of acute gouty arthritis and to verify the clinical efficacy and safety of the drug through a clinical trial.</p><p><b>METHODS</b>A randomized and controlled clinical trial was designed based on clinical epidemiological principles. A total of 107 patients with acute gouty arthritis were enrolled and randomly assigned to four groups. The first group (Group I) included 27 patients taking gout prescription I; the second group (Group II) included 27 patients taking gout prescription II; the third group (Group III) included 28 patients taking gout prescription III; and the fourth group (control group) included 25 patients taking indomethacin and Benzobromarone as a control group. The duration of the treatment in all 4 groups was two weeks. After the treatment, the index of blood uric acid, blood leukocyte count, score of clinical symptoms, etc. were observed and measured.</p><p><b>RESULTS</b>The total clinical effective rate of the three different modified prescriptions of the Simiao Pill was above 96%, significantly superior to that of the control group (68%, P<0.05). In terms of the improvement of main symptoms, the scores of four symptoms in all TCM treatment and control groups decreased after treatment, with statistically significant differences (P<0.05). Moreover, the scores markedly fell more so in the three Chinese herb groups than in the control group, and especially in Group III (P<0.05). There was a statistically significant difference in blood uric acid values before and after the treatment in the same group but no significant inter-group difference was seen.</p><p><b>CONCLUSION</b>The modified prescriptions, based on the clinical research, clinical experience and traditional Chinese medicine theory, did show a better effect than Western medicine in this clinical study. Moreover, the prescriptions were precise, with the herbs inexpensive and readily available. The patients had good compliance with less adverse reactions noted. The modified prescription has a favorable prospect for future development and is worthy of further blind trials with larger samples.</p>