Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms.

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.

Study on inhibitory effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating the upstream and downstream cytokines of type Ⅱ innate lymphoid cells / 中国药房

OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

Inhibition of U-II/UT signaling ameliorates cystitis-associated bladder hyperactivity by targeting the RhoA/Rho-kinase pathway.

Urotensin II (U-II) and its receptor (UT) are involved in the pathogenesis of various diseases; however, their association with the development of cystitis has not been elucidated. The present study was designed to investigate the functional role of U-II/UT signaling in cyclophosphamide (CYP)-induced cystitis. A total of 60 female rats were randomly divided into the control and CYP-treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP-treated group. The protein and mRNA expression levels of U-II and UT were significantly enhanced in rat bladder tissues of the CYP-treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal-like cells. The selective antagonist of UT, SB657510 (10 µm), significantly suppressed the CYP-induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP-treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho-associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho-kinase inhibitor Y-27632 (10 µm), the inhibitory effects of SB657510 (10 µm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U-II/UT signaling promoted the development of cystitis-associated-bladder hyperactivity by targeting the RhoA/Rho-kinase pathway, indicating that the U-II/UT signaling could serve as a novel target for the treatment of interstitial cystitis/bladder pain syndrome.

Preparation, amino acid composition, and in Vitro antioxidant activity of okra seed meal protein hydrolysates.

To improve the utilization of okra seed, acidic and enzymatic hydrolyses of producing protein hydrolysates were respectively optimized by orthogonal experiment and response surface methodology using the degree of hydrolysis (DH) as evaluating index. Amino acid composition and antioxidant capacity in vitro of two kinds of hydrolysates were both analyzed. The degree of acidic hydrolysis was 58.53 ± 1.92% under the following optimized condition: hydrolyzing time 40 hr, temperature 95°C, ratio of acid solution to okra seed meal (OSM) powder was 5:1 (V:W/ml:g), and hydrochloric acid concentration was 18% (W/W). The degree of enzymatic hydrolysis was 16.26 ± 0.56% under the optimized condition: hydrolyzing time 8.20 hr, ratio of buffer to OSM powder was 10:1, and enzyme dosage was 3,100 International Units (IU) g-1. Enzymatic hydrolysates had a fuller range of amino acids and antioxidant capacity than acidic hydrolysates. The results provide technical support for the expansion of okra seed utilization.

[Infraoccipital needle-knife for cervical vertigo].

OBJECTIVE: To observe the clinical effect differences between infraoccipital needle-knife and massage for cervical vertigo. METHODS: A total of 366 patients with cervical vertigo were randomly assigned into a needle-knife group (186 cases) and a massage group (180 cases). With cases dropping excluded, 183 cases in the needle-knife group and 176 cases in the massage group were included. Needle-knife was used at Fengchi (GB 20), infraoccipital ashi point, etc. in the needle-knife group. The treatment was given for one course, once three days, 5 times as one course. The traditional massage was applied in the massage group for one course, including systematic stroking, kneading, and the application of pressure and plucking, etc., once every two days and 7 times as one course. The dizziness handicap inventory (DHI) score was observed before and after treatment, as well as 3, 6, and 12 months after treatment. The effects were also evaluated. RESULTS: The total effective rate was 92.3% (169/183) in the needle-knife group, which was better than 85.2% (150/176) in the massage group (P<0.05). Compared with those before treatment, the DHI scores at all the observation time points after treatment were improved in the two groups (all P<0.05), with better improvements after treatment as well as 3 and 6 months after treatment in the needle-knife group (all P<0.05). There was no significant difference in the improvement of DHI scores between the two groups 12 months after treatment (P>0.05). The recurrence rate was 10.3% (12/117) in the needle-knife group, and it was 10.7% (11/103) in the massage group 12 months after treatment (P>0.05). CONCLUSIONS: Infraoccipital needle-knife achieves apparent effect for cervical vertigo, which is superior to massage in short period.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

OBJECTIVE: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. BACKGROUND: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. METHODS: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. RESULTS: Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. CONCLUSIONS: These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.

Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.

Effect of dark rearing on development of visual sense and proteomics of visual cortex in growing rat / 中华实验眼科杂志

Background Previous study on critical period plasticity in local cortical circuits primarily was only to test the role of some proteins in visual cortex on visual development based on the existed neural signals expression system,but whole containing proteins analysis in cortical circuits is lack.To perform a whole containing proteins analysis has an important significance for critical period plasticity study.Objective This study was to investigate the influence of dark rearing on visual sense and proteomics in visual cortex for growing rat.Methods Two SD female rats were fed in two cages together with 12 newborn rats on the same day respectively,and half number of newborn rats were exchanged each other from first day after delivering and marked by eartipping.The newborn rats in a cage were bred in the dark environment for 40 days,and newborn rats in other cage were bred in the nature environment as controls.The blink response of rats to nearby object was examined and compared between the two groups of rats.Then three rats from two cages were sacrificed respectively and bilateral primary visual cortex tissue was isolated.Proteomics in rat primary visual cortex was detected by two-dimensional electrophoresis and mass spectrometry and the result was checked from database.Then the survival rats in the dark environment returned to the nature environment for 10 days,and the blink response of rats to nearby object were compared with that of agematched rats in the natural environment.The use and care of experimental rats followed the instruction of Ethic Committee of Nankai University.Results The blink response of rats was (0.33 ± 0.35) times in the dark environment for 40-day group,and that in the natural environment for 40-day group was (6.42±0.68) times,with a significant difference between them (t =24.38,P＜0.01).After returned to natural environment for 10 days,the blink response times of rats were less than those of the natural environment group ([5.00±1.22] times vs.[6.11±0.59]times),but this change was not statistically significant (t =2.09,P＞0.05).Two-dimensional electrophoresis and mass spectrometry assay revealed that 36 different proteins in visual cortex were found in the dark-feed rats compared with the natural environment rats,including 26 loss proteins and 10 extra proteins.Among the different proteins,Eps 15 homology domain-containing protein-3 (EHD3),tubulin alpha-1A chain and 2 ',3 '-cyclic-nucleotide 3 ' phosphordiesterase were the known proteins.Conclusions Dark rearing cause reversible visual loss in critical period plasticity newborn rat,and the change of proteomics in visual cortex is probably an affecting factor.

Effects of Wenshen Huatan Recipe on the renal function and foe blood lipids of patients with early-middle stage chronic renal insufficiency of Pi-Shen yang deficiency / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the clinical effectiveness of Wenshen Huatan Recipe (WHR) in treating early-middle stage chronic renal insufficiency (CRI) of Pi-Shen yang deficiency syndrome (PSYDS).</p><p><b>METHODS</b>Ninety early-middle stage CRI patients of PSYDS were recruited and randomly assigned to the treated group (60 cases) and the control group (30 cases) in the ratio of 2:1. All patients received conventional and symptomatic treatment, but those in the treated group received WHR additionally. The observation was lasted for six months. The total efficacy, the Chinese medicine syndrome integral, and indices of the renal functions [including serum creatinine (SCr), blood urea nitrogen (BUN), creatinine clearance (CCr), serum cystatin C (Cys-C)], blood lipids [total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C)], as well as adverse reactions were observed before and after treatment.</p><p><b>RESULTS</b>After six months of treatment, the total effective rate in treated group was 70.0% (42/60), which was obviously higher than that in the control group [43.3% (13/30), P < 0.05]. The Chinese medicine symptoms in the treated group were obviously improved, showing statistical difference between the two groups (P < 0.01). Better effects in lowering SCr, BUN, Cys-C, and LDL-C and increasing CCr were obtained in the treated group than in the control group (P < 0.05).</p><p><b>CONCLUSION</b>WHR could postpone the progression of CRI, improve the lipid metabolism, indicating certain therapeutic efficacy could be obtained in treating early-middle stage CRI from sputum theory.</p>

Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary pharmacokinetics of Yixintong sustained release tablets / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method to determine vitexin-rhamnoside in plasma of Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong sustained release tablets in Beagle dogs.</p><p><b>METHOD</b>A newly-developed HPLC method using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0.5% acetic acid (1:1:19.4:78.6) as mobile phase was validated, and then was employed to determine vitexin-rhamnoside in plasma of Beagle dogs after oral administration of Yixintong sustained release tablets and general tablets. The main pharmacokinetic parameters were estimated by pharmacokinetic program 3p87. The non-compartmental pharmacokinetic parameters were also calculated on basis of the statistic moment theory.</p><p><b>RESULT</b>The pharmacokinetic profiles of Yixintong sustained release tablets and the general tablets were fitted to a one-and two-compartment open model, respectively. The T1/2, Tmax, AUC0-infinity and MRT for Yixintong sustained release tablets were 5.22 h, 4.0 h, 6,792.75 ng x h x mL(-1) and 8.4 h, respectively, compared with 8.94 h, 1.0 h, 5,880.4 ng x h x mL(-1) and 6.1 h for the general tablets. The relative bioavailability of the Yixintong sustained release tablets was 115.5% in Beagle dogs.</p><p><b>CONCLUSION</b>The sustained-release characteristic of Yixintong sustained release tablets were confirmed by pharmacokinetic study.</p>

Clinical study on treatment of chronic renal insufficiency based on sputum and blood stasis theory / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Wenshen Huatan Recipe (WHR) on patients with early or middle stage chronic renal insufficiency (CRI) and investigate the clinical validity of applying sputum and blood stasis theory in treating CRI.</p><p><b>METHODS</b>Sixty CRI patients were selected and randomly assigned to the treated group (n = 32) and the control group (n = 28), all received conventional and symptomatic treatment, but those in the treated group were given WHR additionally. Two months were taken as one treatment course and the study lasted for 3 treatment courses. Total effective rate was assessed at the end of the 2nd and 6th month, changes of clinical symptom scores of TCM, and levels of blood urea nitrogen (BUN) and serum creatinine (SCr) in the two groups were observed as well.</p><p><b>RESULTS</b>The total effective rate of the 2nd and 6th month was 68.8% and 75.0% respectively in the treated group and 42.9% and 35.7% in the control group respectively, the difference between the two groups was significant (P < 0.05). Symptoms were improving along with the increasing medication time, and the improvement between the two groups was significant (P<0.01). Levels of SCr and BUN were significantly lowered in the treated group after 2-month and 6-month treatment (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>WHR can significantly improve the clinical effect of treatment on CRI during early-middle stage, suggesting that CRI could be treated based on sputum and blood stasis theory with definite clinical efficacy.</p>

[Comparative research of thrombosis animal model induced byendotoxin in combination with carrageenan in different animals].

OBJECTIVE: To compare the development of thrombosis animal model induced by endotoxin(LPS) in combination with carrageenan (Ca) in different animals. METHOD: Two species of rats (SD and Wistar) and three species of mice (Kunming, ICR and Balb/c mice) were employed in the study. The animals of each species were randomly divided into control group and model group (LPS/Ca treatment). The animals in the model group were pretreated with Ca ip at the doses of 25 mg x kg(-1) for rats and 150 mg x kg(-1) for mice, and then treated by LPS iv sixteen hours later, while in the control group were given normal saline (NS). Thrombosis in tails was observed at 24 h after LPS iv. Hematologic parameters were tested for all the animals from each species, and the blood concentration of TNFalpha and IL-6 at different time in SD and Wistar rats were measured. RESULT: LPS/Ca combinatory treatment could induce thrombosis animal model in all five animal species, and the thrombus could be clearly observed on the tails. All species had the similar change in hematologic parameters characterized as the significant decrease of white blood cells and platlets. Inflammatory factors TNFalpha and IL-6 could be largely induced in blood of both SD and Wistar rats at 2 h after LPS iv, but both inflammatory factors only transitorily exist in blood at the early stage of thrombosis model formation. CONCLUSION: LPS/Ca combinatory treatment can successfully induce thrombosis animal model in all tested animal species, and thus this model has extensive animal candidates. The secretion of a large amount of inflammatory factors plays a crucial role in the formation of thrombosis animal model.

Relationship among endometriosis,estrogen and progesterone receptors,and their subtypes / 上海第二医科大学学报

The growth and invasion of ectopic endometrium in endometriosis depends on hormone which will work in combination with its receptors.This review introduces the construction,function,gene,subtypes of estrogen receptor and progesterone receptor and their expressions in eutopic and ectopic endometrium,and explores their significance in the genesis,development,treatment and prognosis of endometriosis.

Expression of ER? and PR in ectopic and eutopic endometrium of adenomyosis treated by mifepristone in different menstrual cycles / 上海第二医科大学学报

Objective To study the effects of mifepristone on the expression of estrogen receptor(ER)? and progesterone receptor(PR) in the endometrium of patients with adenomyosis in different menstrual cycles. Methods Forty-seven patients with adenomyosis and 15 normal subjects were divided into 3 groups: mifepristone group(n=24),non-drug group(n=23) and control group(n=15).The expression of ER? and PR in eutopic,ectopic and normal endometrium in proliferative phase and secretory phase were detected by immunohistochemistry. Results In non-drug group,the expression of ER? and PR in ectopic endometrial glandular and stromal cells was significantly lower than that in eutopic and normal endometrium(P0.05).The expression of ER? and PR in both ectopic and eutopic endometrial glandular and stromal cells in mifepristone group was lower than that in the non-drug group(P

Comparative research of thrombosis animal model induced byendotoxin in combination with carrageenan in different animals / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the development of thrombosis animal model induced by endotoxin(LPS) in combination with carrageenan (Ca) in different animals.</p><p><b>METHOD</b>Two species of rats (SD and Wistar) and three species of mice (Kunming, ICR and Balb/c mice) were employed in the study. The animals of each species were randomly divided into control group and model group (LPS/Ca treatment). The animals in the model group were pretreated with Ca ip at the doses of 25 mg x kg(-1) for rats and 150 mg x kg(-1) for mice, and then treated by LPS iv sixteen hours later, while in the control group were given normal saline (NS). Thrombosis in tails was observed at 24 h after LPS iv. Hematologic parameters were tested for all the animals from each species, and the blood concentration of TNFalpha and IL-6 at different time in SD and Wistar rats were measured.</p><p><b>RESULT</b>LPS/Ca combinatory treatment could induce thrombosis animal model in all five animal species, and the thrombus could be clearly observed on the tails. All species had the similar change in hematologic parameters characterized as the significant decrease of white blood cells and platlets. Inflammatory factors TNFalpha and IL-6 could be largely induced in blood of both SD and Wistar rats at 2 h after LPS iv, but both inflammatory factors only transitorily exist in blood at the early stage of thrombosis model formation.</p><p><b>CONCLUSION</b>LPS/Ca combinatory treatment can successfully induce thrombosis animal model in all tested animal species, and thus this model has extensive animal candidates. The secretion of a large amount of inflammatory factors plays a crucial role in the formation of thrombosis animal model.</p>