Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Current Tracking on Effectiveness and Mechanisms of Acupuncture Therapy: A Literature Review of High-Quality Studies.

The scientific evidence of acupuncture studies has been improved in recent years, and one of the important manifestations is that more and more acupuncture clinical trials and mechanism researches have been published in the source periodicals of Science Citation Index (SCI). This study summarized the dominant diseases of acupuncture focusing on of acupuncture efficacy and mechanisms, and discussed the existing problems, highlighting the direction of future developments. Most clinical studies were published in journals with journal impact factor (JIF) score of 10 or above, and majority of the basic researches had JIF scores of 5 to 10. The above literature were further divided according to the International Classification of Diseases (ICD). The most concerned diseases in these articles were neurological diseases, musculoskeletal system and connective tissue diseases, tumor and digestive system diseases. The therapeutic effect and mechanism of acupuncture on each kind of disease were summarized. The results showed that the therapeutic effect of acupuncture on nerve injury focused on the anti-oxidation pathway, neuroprotective and anti-inflammatory processes. The antiinflammatory effect also played an important role in the treatment of musculoskeletal diseases. The analgesic effect was underlined in most of these studies. Clinical trials were well carried out on acupuncture curative effect of tumor complications and side effects of chemo-radiotherapy, but the potential mechanisms have not been clarified. Somato-visceral reflex was suggested to be strongly associated with the effects of acupuncture changing the motor activity of the gastrointestinal tract. Functional magnetic resonance imaging studies indicated that non-specific effects play important roles in acupuncture analgesia. Lines of evidence have pointed out that the regulation of neuro-endocrine-immune networks may be a common switch of acupuncture on different nerve system diseases.

PI3K/Akt signaling pathway in the basolateral amygdala mediates the rapid antidepressant-like effects of trefoil factor 3.

Depression is one of the most common and debilitating psychiatric illnesses around the world, but the current antidepressants used to treat depression have many limitations. Progressively more studies have shown that neuropeptide systems are potential novel therapeutic targets for depression. However, whether the neuropeptide trefoil factor 3 (TFF3) participates in the development of depression has not been examined. In the current experiments, we assessed the antidepressant effects of TFF3 using the forced swim test (FST), tail suspension test (TST), and chronic mild stress (CMS) paradigm. Furthermore, we determined the mechanism that underlies the antidepressant-like effects of TFF3 in the rat FST. TFF3 dose-dependently reduced immobility time in both FST and TST. CMS elevated plasma TFF3 and decreased basolateral amygdala (BLA) TFF3 levels in rats, and acute TFF3 (0.1 mg/kg, i.p.) treatment reversed the depressive-like behaviors induced by CMS. Furthermore, TFF3 (0.1 mg/kg, i.p.) significantly increased Fos expression in the BLA, medial prefrontal cortex, and hypothalamus in rats subjected to the FST. Intra-BLA infusions of TFF3 (1 ng/side) exerted rapid antidepressant-like effects in the rat FST. Additionally, acute systemic TFF3 administration increased the level of phosphorylated-Akt (p-Akt) in the BLA. Finally, intra-BLA infusions of LY294002 (5 mM/side), a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly blocked the antidepressant-like effect of TFF3. Our results demonstrated that TFF3 exerts antidepressant-like effects that might be mediated by the PI3K/Akt signaling pathway in the BLA. These findings suggest a novel neuropeptide system target in the development of new antidepressants.

Green tea polyphenols produce antidepressant-like effects in adult mice.

Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like effects and the possible mechanism of action of green tea in widely used mouse models of depression. Mice were orally administered green tea polyphenols (GTP; 5, 10 and 20mg/kg) for 7days and assessed in the forced swimming test (FST) and tail suspension test (TST) 60min after the last GTP administration. Serum corticosterone and adrenocorticotrophic hormone (ACTH) levels were also determined immediately after the FST. Green tea polyphenols significantly reduced immobility in both the FST and TST but did not alter locomotor activity in the open field test, suggesting that GTP has antidepressant-like effects, and this action did not induce nonspecific motor changes in mice. Green tea polyphenols also reduced serum corticosterone and ACTH levels in mice exposed to the FST. The present study demonstrated that GTP exerts antidepressant-like effects in a mouse behavioral models of depression, and the mechanism may involve inhibition of the hypothalamic-pituitary-adrenal axis.

Auricle reconstruction with a nickel-titanium shape memory alloy as the framework.

OBJECTIVE: The objective of this study is to explore the biocompatibility and implantability of a nickel-titanium (NiTi) alloy in auricle reconstruction. METHODS AND MATERIALS: Twelve New Zealand rabbits underwent subcutaneous implantation with a NiTi alloy framework shaped like the human auricle under general anesthesia. The implant was inserted after skin expansion. Implant vascularization was evaluated at months 1, 3, 6, 9, and 12 after implantation by histologic analysis. Immunohistochemical methods were used to examine expression of vascular endothelial growth factor in tissue around the implant. The fibrovascular ingrowth rate of implants was determined by bone scanning using (99m)Tc-PYP. The surface of the NiTi alloy implant was examined microscopically with scanning electron microscopy. RESULT: The implant harvested showed only partial vascularization at 1 month and completely vascularized at 3 months. The amount of vascular endothelial growth factor-positive cells was markedly increased at 6 months and reached the highest number at 3 months. The fibrovascular ingrowth rate of implant was assessed by (99m)Tc-PYP bone scan using ratios of (99m)Tc-PYP activity in placement regions versus the contralateral normal region. One rabbit had exposure of the NiTi alloy framework as a result of overlying skin flap necrosis. It was rescued with animal skin without the complete removal of the framework. All the other rabbits tolerated the implant well, and there were no complications. CONCLUSION: The NiTi alloy implant represents an alternative implant for auricular reconstruction.