Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.</p> <p>Methods</p> <p>Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons.</p> <p>Results</p> <p>In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation.</p> <p>Conclusions</p> <p>In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.</p

NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

<p>Abstract</p> <p>Background</p> <p>Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear.</p> <p>Objective</p> <p>Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells).</p> <p>Methods</p> <p>Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay.</p> <p>Results</p> <p>These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47^phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration.</p> <p>Conclusion</p> <p>These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA.</p

Impaired Inflammatory Responses in Murine Lrrk2-Knockdown Brain Microglia

LRRK2, a Parkinson's disease associated gene, is highly expressed in microglia in addition to neurons; however, its function in microglia has not been evaluated. Using Lrrk2 knockdown (Lrrk2-KD) murine microglia prepared by lentiviral-mediated transfer of Lrrk2-specific small inhibitory hairpin RNA (shRNA), we found that Lrrk2 deficiency attenuated lipopolysaccharide (LPS)-induced mRNA and/or protein expression of inducible nitric oxide synthase, TNF-α, IL-1β and IL-6. LPS-induced phosphorylation of p38 mitogen-activated protein kinase and stimulation of NF-κB-responsive luciferase reporter activity was also decreased in Lrrk2-KD cells. Interestingly, the decrease in NF-κB transcriptional activity measured by luciferase assays appeared to reflect increased binding of the inhibitory NF-κB homodimer, p50/p50, to DNA. In LPS-responsive HEK293T cells, overexpression of the human LRRK2 pathologic, kinase-active mutant G2019S increased basal and LPS-induced levels of phosphorylated p38 and JNK, whereas wild-type and other pathologic (R1441C and G2385R) or artificial kinase-dead (D1994A) LRRK2 mutants either enhanced or did not change basal and LPS-induced p38 and JNK phosphorylation levels. However, wild-type LRRK2 and all LRRK2 mutant variants equally enhanced NF-κB transcriptional activity. Taken together, these results suggest that LRRK2 is a positive regulator of inflammation in murine microglia, and LRRK2 mutations may alter the microenvironment of the brain to favor neuroinflammation

Bacteria-inducing legume nodules involved in the improvement of plant growth, health and nutrition

Bacteria-inducing legume nodules are known as rhizobia and belong to the class Alphaproteobacteria and Betaproteobacteria. They promote the growth and nutrition of their respective legume hosts through atmospheric nitrogen fixation which takes place in the nodules induced in their roots or stems. In addition, rhizobia have other plant growth-promoting mechanisms, mainly solubilization of phosphate and production of indoleacetic acid, ACC deaminase and siderophores. Some of these mechanisms have been reported for strains of rhizobia which are also able to promote the growth of several nonlegumes, such as cereals, oilseeds and vegetables. Less studied are the mechanisms that have the rhizobia to promote the plant health; however, these bacteria are able to exert biocontrol of some phytopathogens and to induce the plant resistance. In this chapter, we revised the available data about the ability of the legume nodule-inducing bacteria for improving the plant growth, health and nutrition of both legumes and nonlegumes. These data showed that rhizobia meet all the requirements of sustainable agriculture to be used as bio-inoculants allowing the total or partial replacement of chemicals used for fertilization or protection of crops

Ultrasound-guided percutaneous carpal tunnel release in patients on hemodialysis: early experiences and clinical outcomes

Ping-Hui Wang,1 Chia-Lung Li,2,3 Chung-Jung Shao,4 Kuo-Chen Wu,5 Tai-Chang Chern,6 I-Ming Jou7,81Department of Orthopedics, Chi-Mei Medical Center, Tainan 710, Taiwan; 2Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 3Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; 4Department of Orthopedics, Tainan Municipal Hospital, Tainan 709, Taiwan; 5Department of Orthopedics, Kuo General Hospital, Tainan, Taiwan; 6Chern Tai-Chang Orthopedic Clinic, Pingtung 900, Taiwan; 7Department of Orthopedics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 8Department of Orthopedics, National Cheng Kung University, Tainan, TaiwanPurpose: The purpose of the current study was to evaluate the effectiveness of ultrasound-guided percutaneous carpal tunnel release in hemodialysis patients with carpal tunnel syndrome.Methods: From February 2009 to April 2013, a prospective review of 113 consecutive cases of ultrasound-guided percutaneous carpal tunnel release was carried out in 84 hemodialysis patients. Results were analyzed by clinical subjective scale, two self-administered questionnaires, and functional evaluations at seven time points (1&nbsp;week and 1, 3, 6, 12, 18, and 24&nbsp;months).Results: Satisfactory symptom improvement in patients was 82%, 80%, 86%, 89%, 90%, 91%, and 90% at 1&nbsp;week and 1, 3, 6, 12, 18, and 24&nbsp;months postoperatively, respectively. Moderate pain was suffered in 11.5% of patients within 1&nbsp;week, 8.8% within 1&nbsp;month, 2.7% within 3&nbsp;months, and none after 12&nbsp;months postoperatively. Static two-point discrimination and Semmes&ndash;Weinstein monofilament examinations presented significant improvements after 1&nbsp;week and 1&nbsp;month postoperatively and with time. Postoperative grip power demonstrated recovery and a significant increase after 3 and 6&nbsp;months postoperatively. Three-jaw chuck-pinch strength showed significant increase after 1&nbsp;month postoperatively. There were no operative complications.Conclusion: Ultrasound-guided percutaneous carpal tunnel release is an effective and safe procedure in hemodialysis patients with carpal tunnel syndrome. The advantages include a less invasive procedure, no tourniquet needed, only limited infiltration anesthesia, minimal soft-tissue exploration, and relatively short operation time. Our data suggest this technique can reliably relieve clinical symptoms, with early restoration of grip and pinch strength.Keywords: carpal tunnel, hemodialysis, ultrasound, percutaneous releas

Differences in primary sites of infection between zoonotic and human tuberculosis : results from a worldwide systematic review

Tuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases