The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Caffeine Impaired Acupuncture Analgesia in Inflammatory Pain by Blocking Adenosine A1 Receptor.

Caffeine consumption inhibits acupuncture analgesic effects by blocking adenosine signaling. However, existing evidence remains controversial. Hence, this study aimed to examine the adenosine A1 receptor (A1R) role in moderate-dose caffeine-induced abolishing effect on acupuncture analgesia using A1R knockout mice (A1R-/-). We assessed the role of A1R in physiological sensory perception and its interaction with caffeine by measuring mechanical and thermal pain thresholds and administering A1R and adenosine 2A receptor antagonists in wild-type (WT) and A1R-/- mice. Formalin- and complete Freund's adjuvant (CFA)-induced inflammatory pain models were recruited to explore moderate-dose caffeine effect on pain perception and acupuncture analgesia in WT and A1R-/- mice. Moreover, a C-fiber reflex electromyogram in the biceps femoris was conducted to validate the role of A1R in the caffeine-induced blockade of acupuncture analgesia. We found that A1R was dispensable for physiological sensory perception and formalin- and CFA-induced hypersensitivity. However, genetic deletion of A1R impaired the antinociceptive effect of acupuncture in A1R-/- mice under physiological or inflammatory pain conditions. Acute moderate-dose caffeine administration induced mechanical and thermal hyperalgesia under physiological conditions but not in formalin- and CFA-induced inflammatory pain. Moreover, caffeine significantly inhibited electroacupuncture (EA) analgesia in physiological and inflammatory pain in WT mice, comparable to that of A1R antagonists. Conversely, A1R deletion impaired the EA analgesic effect and decreased the caffeine-induced inhibitory effect on EA analgesia in physiological conditions and inflammatory pain. Moderate-dose caffeine administration diminished the EA-induced antinociceptive effect by blocking A1R. Overall, our study suggested that caffeine consumption should be avoided during acupuncture treatment. PERSPECTIVE: Moderate-dose caffeine injection attenuated EA-induced antinociceptive effect in formalin- and CFA-induced inflammatory pain mice models by blocking A1R. This highlights the importance of monitoring caffeine intake during acupuncture treatment.

Effect of enzymolytic soybean meal supplementation on performance, nitrogen excretion, serum biochemical parameters and intestinal morphology in broilers fed low-protein diets.

OBJECTIVE: The objective of this study was to investigate the effect of supplementation with enzymolytic soybean meal (ESBM) on broilers fed low crude protein (CP) diets. METHODS: A total of 360 one-day-old broilers were randomly assigned to six treatments with 6 replicates per treatment and 10 chicks per replicate for a period of 42 days. Chicks were fed a basal standard high-CP diet as a positive control (PC), a low-CP diet (reducing 10 g/kg CP from the PC) as a negative control (NC), or an NC + 0.5%, 1.0%, 1.5%, or 2.0% ESBM diet. RESULTS: Compared to chicks fed the PC, chicks fed the NC had a decreased body weight gain (BWG, p<0.05) from 1 to 42 days, but supplementation with 2.0% ESBM restored BWG (p<0.05) and even linearly improved the feed conversion rate (FCR, p<0.05). Digestibility of CP and ether extract was increased (p<0.05) in chicks fed a 1.0% ESBM diet compared to the PC. With increasing levels of ESBM, nitrogen (N) excretion decreased (p<0.05). The addition of ESBM to the diet did not affect (p>0.05) serum concentrations of total protein, albumin and total cholesterol but led to a descending trend in triglycerides and an ascending trend in calcium and urea N at 42 days (p<0.10). There were no differences (p>0.05) in villus height (VH), crypt depth (CD), and VH/CD (V/C) of the duodenum and jejunum between the PC and NC at both 21 days and 42 days, while increasing dietary ESBM levels linearly (p<0.05) decreased CD and increased V/C of the duodenum and jejunum at both 21 days and 42 days. CONCLUSION: The findings indicated that ESBM could be used in broiler low-CP diets to improve production performance, decrease N excretion, and enhance intestinal health.

Adrenal sympathetic nerve mediated the anti-inflammatory effect of electroacupuncture at ST25 acupoint in a rat model of sepsis.

Acupuncture plays a vital anti-inflammatory action in sepsis by activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating the sympathoadrenal medullary pathway and evaluate EA's anti-inflammatory effect on sepsis. To determine the optimum parameter of EA at homotopic acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley rats were evaluated by in vivo electrophysiological recording, and the levels of norepinephrine (NE) and its metabolites normetanephrine (NMN) were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rats were given an intraperitoneal injection of lipopolysaccharide (LPS) to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1ß, and IL-10 were evaluated after EA application. We observed that 3 mA is the optimal intensity for activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3 mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1ß and upregulated anti-inflammatory cytokine IL-10 compared to the LPS-treated group. Overall, our data suggested that 3 mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect in sepsis.

Probiotics protect against hepatic steatosis in tris (2-chloroethyl) phosphate-induced metabolic disorder of mice via FXR signaling.

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.

Selenium Status Affects Hypertrophic Growth of Skeletal Muscle in Growing Zebrafish by Mediating Protein Turnover.

BACKGROUND: Selenium (Se) status is closely related to skeletal muscle physiological status. However, its influence on skeletal muscle growth has not been well studied. OBJECTIVES: This study aimed to analyze the impacts of overall Se status (deficient, adequate, and high) on skeletal muscle growth using a growing zebrafish model. METHODS: Zebrafish (1.5-mo-old) were fed graded levels of Se (deficient: 0.10 mg Se/kg; marginally deficient: 0.22 mg Se/kg; adequate: 0.34 mg Se/kg; high: 0.44, 0.57, and 0.69 mg Se/kg) as Se-enriched yeast for 30 d. Zebrafish growth, and Se accumulation, selenoenzyme activity, selenotranscriptome profiles, and oxidative status in the whole body, and selenotranscriptome profiles, histological characteristics, biochemicals, and gene and protein expression profiles related to muscle growth in the skeletal muscle were analyzed by model fitting and/or 1-factor ANOVA. RESULTS: Se status biomarkers within the whole body and skeletal muscle indicated that 0.34 mg Se/kg was adequate for growing zebrafish. For biomarkers related to skeletal muscle growth, compared with 0.34 mg Se/kg, 0.10 mg Se/kg decreased the white muscle cross-sectional area (WMCSA) and the mean diameter of white muscle fibers (MDWMF) by 14.4%-15.1%, inhibited protein kinase B-target of rapamycin complex 1 signaling by 63.7%-68.5%, and stimulated the autophagy-lysosome pathway by 1.07 times and the ubiquitin-proteasome pathway (UPP) by 96.0% (P < 0.05), whereas 0.22 mg Se/kg only decreased the WMCSA by 7.8% (P < 0.05); furthermore, 0.44 mg Se/kg had no clear effects on skeletal muscle biomarkers, whereas 0.57-0.69 mg Se/kg decreased the WMCSA and MDWMF by 6.3%-25.9% and 5.1%-21.3%, respectively, and stimulated the UPP by 2.23 times (P < 0.05). CONCLUSIONS: A level of 0.34 mg Se/kg is adequate for the growth of zebrafish skeletal muscle, whereas ≤0.10 and ≥0.57 mg Se/kg are too low or too high, respectively, for maintaining efficient protein accretion and normal hypertrophic growth.

Purification, characterization, and in vitro antitumor activity of a novel glucan from the purple sweet potato Ipomoea Batatas (L.) Lam.

A novel glucan PSPP-1 (18.3 kDa) was purified from the foot tuber of purple sweet potato Ipomoea Batatas (L.) Lam. Its backbone was composed of →4)-α-d-Glcp(1→ glycosyl, and branching at the O-2, O-3, and O-6 positions with α-d-Glcp(1→ residues. X-ray diffraction experiment showed that PSPP-1 existed as an amorphous form. Its microstructure was detected via scanning electron microscopy. Its particle size was mainly concentrated at 230 nm in water. Congo red and circular dichroism experiments showed there was no triple-helix conformation. Atomic force microscopy data suggested that its height and width ranged from 1.0 to 6.1 nm and 65 to 210 nm, respectively; its maximum ring diameter and chain length was ∼800 nm and ∼7.0 µm, respectively. Furthermore, it exhibited inhibitory activities on HepG2, LOVO, and MCF-7 cells. Collectively, our data are useful for understanding the structural characteristics of sweet potato polysaccharides, and their application in foods and pharmaceutical areas.

Antibacterial activity of the structurally novel ocotillol-type lactone and its analogues.

A novel series of ocotillol-type lactone derivatives were designed and synthesized in order to study their antibacterial activity and structure-activity relationships. Among which, compounds 4j and 4 m were found to be the most active with minimum inhibitory concentrations (MICs) of 1-4 µg/mL against Gram-positive bacteria and showed low cytotoxicity against MCF-7, HEK-293 and HK-2 cells at their MICs. The antibacterial effect of compound 4 m was characterized further by scanning electron microscopy, cytoplasmic ß-galactosidase leakage assay and UV-visible analysis. The results showed that 4 m may exert its antibacterial effect by damaging bacterial cell membranes and disrupting the function of DNA, both of which could lead to rapid cell death.

Studied on the dynamic adsorption process of Lycium barbarum polysaccharide in the POPC/DPPC monolayers.

In this study, the interaction between Lycium barbarum polysaccharide (LBP) and unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or saturated 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was explored using the Langmuir films technique and atomic force microscopy (AFM). Comparing the pure lipid monolayer with the mixed monolayers, the π-A isotherms of the mixed monolayers shifted to larger molecular areas when LBP was added to the subphase. The compression modulus showed that the compressibility of the monolayer films decreased with the addition of LBP. Adsorption curves revealed that the variation in the surface pressure of LBP with POPC was larger than that with DPPC. This phenomenon was verified by the AFM images and the number of each lipid molecule combining with polysaccharide molecules in the mixed monolayer (Ap value), indicating that hydrophobic interactions between LBP and POPC are stronger than those of DPPC. These findings lay the foundation for exploring the pharmacological mechanism of LBP as an in vivo therapeutic.

Pomegranate extract and exercise provide additive benefits on improvement of immune function by inhibiting inflammation and oxidative stress in high-fat-diet-induced obesity in rats.

BACKGROUND: Obesity is reported to be associated with immune dysfunction and a state of low-grade, chronic inflammation. Either pomegranate extract (PomE) or exercise (Ex) has been shown to have antiobesity, anti-inflammatory and antioxidant effects. Nevertheless, no study has addressed the additive benefits of PomE and Ex on the restoration of obesity-induced immune defects. OBJECTIVE: The present work aims to study the effect of PomE and Ex as a combined intervention on immune function and the underlying mechanism involved in inflammation and oxidative stress in rats with high-fat-diet (HFD)-induced obesity. RESULTS: Our results demonstrate that the combination of PomE and Ex showed additive benefits on inhibition of HFD-induced body weight increase and improvement of HFD-induced immune dysfunction, including (a) attenuating the abnormality of histomorphology of the spleen, (b) increasing the ratio of the CD4+:CD8+ T cell subpopulations in splenocytes and peripheral blood mononuclear cells (PBMC), (c) inhibition of apoptosis in splenocytes and PBMC, (d) normalizing peritoneal macrophage phenotypes and (e) restoring immunomodulating factors in serum. We also find that immune dysfunction in HFD-fed rats was associated with increased inflammatory cytokine secretion and oxidative stress biomarkers, and that the combination of PomE and Ex effectively inhibited the inflammatory response and decreased oxidative damage. CONCLUSIONS: The effect of PomE and Ex as a combined intervention is greater than the effect of either PomE or Ex alone, showing that PomE and Ex may be additively effective in improving immune function in HFD-fed rats by inhibiting inflammation and decreasing oxidative stress.

Effectiveness of aquatic exercise for treatment of knee osteoarthritis: Systematic review and meta-analysis.

OBJECTIVE: This paper presents a systematic review and meta-analysis of the effectiveness of aquatic exercise for treatment of knee osteoarthritis (OA). METHODS: PubMed, the Cochrane Library, Embase, CAMbase, and the Web of Science were screened through to June 2014. Only randomized controlled trials (RCTs) comparing aquatic exercise with control conditions were included. Two authors independently selected trials for inclusion, assessed the included trials, and extracted data. Outcome measures included pain, physical function, joint stiffness, quality of life (QOL), and safety. Pooled outcomes were analyzed using standardized mean difference (SMD). RESULTS: There is a lack of high quality studies in this area. Six RCTs (398 participants) were included. There was moderate evidence for a moderate effect on physical function in favor of aquatic exercise immediately after the intervention, but no evidence for pain or QOL when comparing aquatic exercise with nonexercise. Only one trial reported 3 months of follow-up measurements, which demonstrated limited evidence for pain improvement with aquatic exercise and no evidence for QOL or physical function when comparing aquatic exercise with nonexercise. There was limited evidence for pain improvement with land-based exercise and no evidence for QOL or physical function, when comparing aquatic exercise with land-based exercise according to follow-up measurements. No evidence was found for pain, physical function, stiffness, QOL, or mental health with aquatic exercise immediately after the intervention when comparing aquatic exercise with land-based exercise. Two studies reported aquatic exercise was not associated with serious adverse events. CONCLUSION: Aquatic exercise appears to have considerable short-term benefits compared with land-based exercise and nonexercise in patients with knee OA. Based on these results, aquatic exercise is effective and safe and can be considered as an adjuvant treatment for patients with knee OA. Studies in this area are still too scarce and too short-term to provide further recommendations on how to apply this therapy.

[Clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy].

To observe the clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy patients, totally 65 patients from China-Japan Friendship hospital during 2008-2012 with complete clinical data and received consecutive traditional Chinese medicine and western medicine treatment for more than 3 months were observed changes of traditional Chinese medicine symptom score, part 1 of unified multiple system atrophy rating scale, orthostatic hypotension before treatment and after 3 months treatment. After 3 months treatment, total effective rate of traditional Chinese medicine symptom was 70.8%. Compared with before treatment, score of part 1 of unified multiple system atrophy rating scale was obviously reduced after 3 month treatment (P < 0.001). Ex- cept swallow function without significant improvement, the remaining projects of unified multiple system atrophy rating scale were im- proved obviously (P < 0.05), of which the most obvious differences were orthostatic symptoms, falls and intestinal function (P < 0.001). Orthostatic hypotension after 1 month treatment and 3 month treatment was obviously better than before treatment (P < 0.001). There was no significant difference in orthostatic hypotension between 1 month treatment and 3 month treatment. The research results show that Yisui decoction plus western medicine has a certain effect on improving clinical symptoms of multiple system atrophy patients, especially has a significant effect on orthostatic hypotension, and can maintain a stable clinical effect in a certain period of time.

Zhuanggu Jianxi Decoction () limits interleukin-1 ß-induced degeneration chondrocytes via the caveolin-p38 MAPK signal pathway.

OBJECTIVE: To evaluate the effect of Zhuanggu Jianxi Decoction (, ZGJXD) on interleukin-1 ß (IL-1 ß)-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis. METHODS: Serum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL-1 ß stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II collagen immunocytochemistry. After IL-1 ß-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 ß, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 were examined by real-time polymerase chain reaction. RESULTS: IL-1 ß stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 ß, TNF-α, MMP-3 and MMP-13. However, the IL-1 ß-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs. CONCLUSION: ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.

[Effect of chailing decoction and its active ingredients on experimental nephritis in rats].

OBJECTIVE: To screen the active ingredients of Chailing decoction (CLD) by using rat nephritis model induced by mono-colonal antibody 1-22-3 (mAb) injection. METHODS: The active ingredients of CLD was screened by 5 successive times of experiment. In each time, 28 rats were randomly divided into 4 groups, 7 in each. Group 1 was treated with PBS as control, Groups 2-4 were treated separately with CLD and its various ingredients, the medication was started 5 days before and lasted to 8 days after modeling by peritoneal injection, 13 days totally. All the rats were killed 8 days after modeling to observe the effect of various drugs on proteinuria, morphological change of kidney and biochemical parameters. RESULTS: CLD, Xiaochaihu decoction, various combination of thorowax root and its extract (saikosaponin-d) could reduce urinary protein, inhibit the proliferation of mesangial cell and expansion of extracellular matrix. CONCLUSION: CLD and its active ingredients had inhibition on mAb induced rat model of nephritis, the active is saikosaponin-d.