Treadmill exercise alleviates neuropathic pain by regulating mitophagy of the anterior cingulate cortex in rats / 生理学报

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.

Chang'an II Decoction ( II )-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Chang'an II Decoction ( II ))-containing serum on intestinal epithelial barrier dysfunction in rats.@*METHODS@#Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang'an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang'an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang'an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang'an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot.@*RESULTS@#Chang'an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang'an II-H group. Additionally, Chang'an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus.@*CONCLUSION@#High-dose Chang'an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.

Current situation and disease burden of allergic alveolitis in greenhouse farmers in China / 中国实用内科杂志

Farmer's lung disease(FLD) is a common form of occupational hypersensitivity pneumonitis(HP)(also termed “greenhouse lung”). FLD often occurs in greenhouse farmers due to the long-term exposure to high temperatures, humidity, poor air ventilation and high intensity of microorganism in soils in the closed environment of greenhouses. Greenhouse lung has a high disability rate and poor prognosis if not diagnosed or treated in time, which is a heavy burden to the society. Therefore, it is imperative to pay attention to early identification and epidemiological monitoring, and to evaluate the disease burden, which is of great significance to formulating public health measures to prevent the disease.

Diagnosis of hypersensitivity pneumonitis / 中国实用内科杂志

Hypersensitivity pneumonitis(HP) is an interstitial lung disease(ILD) that is characterized by a complex immunological response within the lung parenchyma to inhalation of an antigen that the individual is sensitized toward. Diagnosis of HP can be challenging and requires the consideration of a detailed history(emphasizing potential antigen exposures), high resolution computed tomography(HRCT) findings, and laboratory and pathological examination. Despite increasing recognition, there is a lack of consensus regarding the definition and diagnostic criteria for HP. This article summarizes the recent developments in diagnosis of hypersensitivity pneumonitis.

Risk factors on chronic obstructive pulmonary disease among greenhouse workers in Liaoning province / 中华流行病学杂志

Objective To study the risk factors of chronic obstructive pulmonary disease (COPD) among greenhouse farmers in Liaoning province.Methods According to geographical differences in Liaoning province,stratified-cluster-random sampling method was used.A total of 5420 greenhouse farmers working in more than 800 greenhouses were investigated with unified questionnaire,physical examination,blood routine examination,blood gas analysis,chest X-ray and pulmonary function tests.Diagnosis of COPD was made according to the criteria for "chronic obstructive pulmonary disease of diagnosis and treatment guidelines" (2007 revision) by the Chinese Respiratory Disease Society.Results The total number of farmers under study was 5880,including 5420 respondants(92.18％) with effective data.Risk factors were found on age(x2＝32.530,P=0.000),time working in greenhouses every day ( x2 =21.311,P =0.000 ),frequency of ventilation ( x2 =9.791,P=0.007) and the location of the greenhouses(x2=73.645,P=0.000).When using SPSS 17.0 for the single factor logistic regression analysis,results indicated that smoking(OR＝1.976,95％CI:1.672-2.334),age ( OR =4.188,95 ％ CI:3.718-4.718 ),greenhouses for fungus ( compared with vegetables,OR=1.302,95％CI:1.016-1.669),flowers and plants (compared with vegetables greenhouses,OR=1.503,95％ CI:1.201-1.880) were the risk factors of COPD among greenhouse farmers while the protective factor was the years of working in the greenhouse (OR=0.684,95％ CI:0.609-0.767).Conclusion The overall morbidity of COPD among greenhouse farmers in Liaoning province was 17.47％ with various risk factors.

Effect of cyclosporine on regulatory T cells and Foxp3 in the peripheral blood of children with chronic aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the expression diversification of CD4(+)CD25(+)CD127(low) regulatory T (Treg) cells and Foxp3 mRNA in the peripheral blood of children with aplastic anemia after the treatment with cyclosporine.</p><p><b>METHODS</b>Fifty children with chronic aplastic anemia were enrolled, among whom 30 received cyclosporine treatment (cyclosporine group) and 20 were treated with conventional methods (conventional group). Twenty healthy children were enrolled as the control group. The expression of CD4(+)CD25(+)CD127(low) Treg cells was detected by flow cytometry. The expression of Foxp3 mRNA was detected by real-time Q-PCR.</p><p><b>RESULTS</b>The expressions of Foxp3 mRNA and CD4(+)CD25(+)CD127(low)Treg cells showed no significant difference between the cyclosporine and the control groups 6 months after treatment. On the contrary, there were significantly lower expressions of both in the conventional group than in the control group (P<0.05). Meanwhile, the cyclosporine group had significantly higher expressions of Foxp3 mRNA and CD4(+)CD25(+)CD127(low) Treg cells than the conventional group (P<0.05).</p><p><b>CONCLUSIONS</b>The expressions of CD4(+)CD25(+)CD127(low) Treg cells and Foxp3 mRNA in children with aplastic anemia increase after cyclosporine treatment.</p>

Detection and significance of CD4+ CD25int/high CD127low regulatory T cells in pediatric aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of CD4+ CD25int/high CD127low regulatory T cells in peripheral blood (PB) and its relation to the quantity of Hb, WBC and platelet (Plt) in children with aplastic anemia (AA).</p><p><b>METHODS</b>Expression of CD4+ CD25int/high CD127low in PB was detected by flow cytometry in 22 children with AA before and after treatment and in 15 healthy controls. The relationships between CD4+CD25highCD127low and the quantity of Hb, WBC and Plt were evaluated.</p><p><b>RESULTS</b>Compared to controls, the percentages of CD4+ CD25+/CD4+, CD4+CD25high/CD4+, CD4+ CD25+ CD127low/CD4+ and CD4+CD25highCD127low/CD4+ in PB of AA patients decreased markedly at the active phase (P﹤0.05). By the recovery phase, the percentages of CD4+CD25+/CD4+, CD4+CD25high/CD4+, CD4+ CD25+ CD127low/CD4+ and CD4+CD25highCD127low/CD4+ increased significantly to the levels similar to the controls. There were significant positive relationships between the expression of CD4+CD25highCD127low cells and the quantity of Hb, WBC and Plt (r=0.499, 0.526, 0.540 respectively; P﹤0.05).</p><p><b>CONCLUSIONS</b>The decrease of the percentage of CD4+CD25int/highCD127low regulatory T cells might be associated with the development of pediatric AA. The CD4+CD25int/highCD127low regulatory T cells can serve as a marker for the evaluation of disease severity as well as a target of further study on immune treatment of AA.</p>

Expression of regulatory T cells and Foxp3 gene in peripheral blood of children with aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the levels of CD4+CD25+CD127(low) regulatory T cells (Tregs) and the expression of Foxp3 gene in peripheral blood of children with aplastic anemia (AA) and to study their roles in the pathogenesis of AA.</p><p><b>METHODS</b>Twenty-one children with chronic AA, 9 with acute AA and 15 healthy children were enrolled. The proportion of CD4+CD25+ CD127low Tregs in CD4+ T cells was evaluated by flow cytometric analysis. The level of Foxp3 mRNA was ascertained by RT-PCR.</p><p><b>RESULTS</b>The percentage of peripheral blood CD4+T cells and CD4+CD25+ and CD4+CD25+CD127(low) Tregs in CD4+T cells in both the acute and chronic AA groups was significantly lower than that in the normal control group (P<0.05).The acute AA group had more decreased CD4+ T cells and CD4+CD25+ and CD4+CD25+CD127(low) Tregs percentage compared with the CAA group (P<0.05). The expression of Foxp3 mRNA in peripheral blood decreased obviously in the acute AA group (0.47 + or - 0.08%) compared with that in the normal control (0.71 + or - 0.12%) and the CAA groups (0.68 + or - 0.14%) (P<0.05).</p><p><b>CONCLUSIONS</b>The low expression of Tregs and Foxp3 mRNA in peripheral blood may be involved in pathogenesis of AA.The more decreased Tregs and Foxp3 mRNA expression in acute AA than chronic AA suggests their possible roles in the assessment of the severity of AA.</p>