The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Phylogenomic analyses of Camellia support reticulate evolution among major clades.

Camellia (Theaceae) is a morphologically highly diverse genus of flowering plants and includes many famous species with high economic value, and the phylogeny of this genus is not fully resolved. We used 95 transcriptomes from 87 Camellia species and identified 1481 low-copy genes to conduct a detailed analysis of the phylogeny of this genus according to various data-screening criteria. The results show that, very different from the two existing classification systems of Camellia, 87 species are grouped into 8 main clades and two independent species, and that all 8 clades except Clade 8 were strongly supported by almost all the coalescent or concatenated trees using different gene subsets. However, the relationships among these clades were weakly supported and different from analyses using different gene subsets; furthermore, they do not agree with the phylogeny from chloroplast genomes of Camellia. Additional analyses support reticulate evolution (probably resulting from introgression or hybridization) among some major Camellia lineages, providing explanation for extensive gene tree conflicts. Furthermore, we inferred that together with the formation of East Asian subtropical evergreen broad-leaved forests, Camellia underwent a radiative divergence of major clades at 23 âˆ¼ 19 Ma in the late Miocene then had a subsequent species burst at 10 âˆ¼ 5 Ma. Principal component and cluster analyses provides new insights into morphological changes underlying the evolution of Camellia and a reference to further clarify subgenus and sections of this genus. The comprehensive study here including a nuclear phylogeny and other analyses reveal the rapid evolutionary history of Camellia.

Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA. METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up. RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG. CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

A cell-cell interaction format for selection of high-affinity antibodies to membrane proteins.

Generating and improving antibodies and peptides that bind specifically to membrane protein targets such as ion channels and G protein-coupled receptors (GPCRs) can be challenging using established selection methods. Current strategies are often limited by difficulties in the presentation of the antigen or the efficiency of the selection process. Here, we report a method for obtaining antibodies specific for whole cell membrane-associated antigens which combines a cell-cell interaction format based on yeast display technology with fluorescence-activated cell sorting of dual fluorescent complexes. Using this method, we were able to direct the affinity maturation of an antagonist antibody specific for the proton-gated ion channel ASIC1a and showed that both the affinity and potency were improved. We were also able to use this method to do kinetic selections to generate clones with better dissociation profiles. In addition, this method was employed successfully to handle the difficult problem of selecting antibodies specific to a GPCR target, the mu-opioid receptor.

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death.

Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion channels in vivo, we showed that they potently protect brain cells from death after an ischemic stroke. Thus, the methodology described here should be general, thereby allowing selection of antibodies to other important ASICs, such as those involved in pain, neurodegeneration, and other conditions.

The anti-tussive, anti-inflammatory effects and sub-chronic toxicological evaluation of perilla seed oil.

BACKGROUND: Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. RESULTS: The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. CONCLUSION: In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.

ZDHXB-101 (3',5-Diallyl-2, 4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways.

Airway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks. The expression of sEH and CYP2J2, the level of 14, 15-epoxyeicosatrienoic acids (EETs), airway remodeling, hyperresponsiveness and inflammation were analyzed to determine the inhibition of sEH. The intragastric administration of 3 or 10 mg/kg ZDHXB-101, which is a structural derivative of natural product honokiol and a novel soluble epoxide hydrolase (sEH) inhibitor, daily for 9 weeks significantly increased the level of 14, 15-EETs by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. ZDHXB-101 reduced the expression of remodeling-related markers such as interleukin (IL)-13, IL-17, MMP-9 N-cadherin, α-smooth muscle actin, S100A4, Twist, goblet cell metaplasia, and collagen deposition in the lung tissue or in bronchoalveolar lavage fluid. Moreover, ZDHXB-101 alleviated AHR, which is an indicator that is used to evaluate the airway remodeling function. The inhibitory effects of ZDHXB-101 were demonstrated to be related to its direct inhibition of the extracellular signal-regulated kinase (Erk1/2) phosphorylation, as well as inhibition of c-Jun N-terminal kinases (JNK) and the signal transducer and activator of transcription-3 (STAT3) signal transduction. These findings first revealed the anti-remodeling potential of ZDHXB-101 lead in chronic airway disease.

Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.

MiR-134-5p attenuates neuropathic pain progression through targeting Twist1.

Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1ß and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3'-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.

Asymmetrical Molecular Decoration of Gold Nanorods for Engineering of Shape-Controlled AuNR@Ag Core-Shell Nanostructures.

Gold-silver (Au@Ag) core-shell nanostructures have a stronger surface plasma response, wider absorption and scattering in the UV-vis-NIR region, and distinctive optical properties, which are widely explored in biosensors, information processing, photothermal therapy, and catalysis. Core-shell nanostructures are usually formed by the deposition of the second metal atoms onto the first core metal particles via the chemical wet method. The conventional approaches for the manipulation of the shape usually were done by homogeneous growth or etching of isotropic nanoparticles. Through in situ modification of the first metal core at the different locations, the different growth model of the second metal can be regulated to control the shapes of core-shell structures. Herein, we modified the gold nanorods (AuNRs) asymmetrically at the end and side parts using thiolated molecules to regulate the morphology of gold nanorod@silver (AuNR@Ag) core-shell nanoparticles. Interestingly, the obvious eccentric nanostructures of AuNR@Ag core-shell nanoparticles were obtained with the increase of the molecular weight of macromolecules modified at the end of AuNRs. Therefore the growth mode was adjusted from Frank-van der Merwe mode to Stranski-Krastanow mode. By changing the length of the hydrocarbon chain and functional groups of the small mercaptan molecules at the side of AuNRs, the silver shell exhibits selective growth at the side of the AuNRs, resulting in heterogeneous core-shell nanoparticles and various shapes of the AuNR@Ag core-shell. Our method opens up a new avenue toward preparing core-shell nanostructures with controlled shapes, and the obtained structures are promising in various applications.

MiR-150 alleviates neuropathic pain via inhibiting toll-like receptor 5.

MicroRNAs (miRNAs) are reported as vital participators in the pathophysiological course of neuropathic pain. However, the underlying mechanisms of the functional roles of miRNAs in neuropathic pain are largely unknown. This study was designed to explore the potential role of miR-150 in regulating the process of neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Overexpression of miR-150 greatly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including COX-2, interleukin IL-6, and tumor necrosis factor (TNF)-α in CCI rats. By bioinformatic analysis, 3'-untranslated region (UTR) of Toll-like receptor (TLR5) was predicted to be a target of miR-150. TLR5 commonly serves as an important regulator of inflammation. Overexpression of miR-150 significantly suppressed the expression of TLR5 in vitro and in vivo. Furthermore, upregulation of TLR5 decreased the miR-150 expression and downregulation of TLR5 increased miR-150, respectively. Overexpression of TLR5 significantly reversed the miR-150-induced suppressive effects on neuropathic pain. In conclusion, our current study indicates that miR-150 may inhibit neuropathic pain development of CCI rats through inhibiting TLR5-mediated neuroinflammation. Our findings suggest that miR-150 may provide a novel therapeutic target for neuropathic pain treatment.

Evidence for Dry Needling in the Management of Myofascial Trigger Points Associated With Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the current evidence of the effectiveness of dry needling of myofascial trigger points (MTrPs) associated with low back pain (LBP). DATA SOURCES: PubMed, Ovid, EBSCO, ScienceDirect, Web of Science, Cochrane Library, CINAHL, and China National Knowledge Infrastructure databases were searched until January 2017. STUDY SELECTION: Randomized controlled trials (RCTs) that used dry needling as the main treatment and included participants diagnosed with LBP with the presence of MTrPs were included. DATA EXTRACTION: Two reviewers independently screened articles, scored methodologic quality, and extracted data. The primary outcomes were pain intensity and functional disability at postintervention and follow-up. DATA SYNTHESIS: A total of 11 RCTs involving 802 patients were included in the meta-analysis. Results suggested that compared with other treatments, dry needling of MTrPs was more effective in alleviating the intensity of LBP (standardized mean difference [SMD], -1.06; 95% confidence interval [CI], -1.77 to -0.36; P=.003) and functional disability (SMD, -0.76; 95% CI, -1.46 to -0.06; P=.03); however, the significant effects of dry needling plus other treatments on pain intensity could be superior to dry needling alone for LBP at postintervention (SMD, 0.83; 95% CI, 0.55-1.11; P<.00001). CONCLUSIONS: Moderate evidence showed that dry needling of MTrPs, especially if associated with other therapies, could be recommended to relieve the intensity of LBP at postintervention; however, the clinical superiority of dry needling in improving functional disability and its follow-up effects still remains unclear.

Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear. In this study, we investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or 16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute inflammation. The lungs of mice exposed to CS showed an increase in the release of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an accumulation of inflammatory cells, indicating high Rac1 activity. The exposure of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1 ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS-exposed mice. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the infiltration of neutrophils and macrophages into the alveolar spaces. Selective inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with CS-mediated inflammation. Rac1 may be a promising therapeutic target for the treatment of CS-induced pulmonary inflammation.

Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids.

A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12µg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5µg/mL) than the parent gatifloxacin (GTFX) (CC50: 125µg/mL). Among them, 61 (MIC: 0.025µg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05µg/mL), GTFX (MIC: 0.78µg/mL) and RIF (MIC: 0.39µg/mL) against MTB H37Rv. The most active conjugate 6k (MIC: 0.06µg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128µg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.

Cryptoporus volvatus polysaccharides attenuate LPS-induced expression of pro-inflammatory factors via the TLR2 signaling pathway in human alveolar epithelial cells.

CONTEXT: Cryptoporus volvatus (Peck) Hubb grows wild in China, and its fruiting bodies have been used traditionally to treat asthma and bronchitis. OBJECTIVES: This study evaluates the anti-inflammatory effect of Cryptoporus polysaccharides (CP) extracted from fruiting bodies of C. volvatus on lipopolysaccharide (LPS)-induced pro-inflammatory factors and the signaling pathways involved in human alveolar epithelial cells. MATERIALS AND METHODS: To evaluate the effects of CP on LPS-induced pro-inflammatory factors, A549 cells were pre-incubated with CP 1, 10, and 100 µg/ml for 1 h and then stimulated with LPS 10 µg/ml for 24 h. The expression of pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), Toll-like receptor 2 (TLR2), and phosphorylation of ERK1/2, p38, and NF-κB p65 were measured by q-PCR, ELISA, and western blotting. RESULTS: CP decreased LPS-induced mRNA expression of MCP-1, TNF-α, and IL-1ß (IC50 = 83.3, 85.2, and 91.6 µg/ml, respectively) and their correspondent protein expression (IC50 = 88.6, 76.4, and 81.6 µg/ml, respectively). Investigation of potential mechanisms indicated that CP 100 µg/ml reduced LPS-induced expression of TLR2 mRNA (66.9%, p < 0.01) and protein (63.2%, p < 0.01) that was a result of the decreased pro-inflammatory factors. LPS induction increased the expression of TLR2 and the phosphorylation of p38 and ERK1/2, NF-kB p65 concomitantly. CP 100 µg/ml inhibited the LPS-induced phosphorylation of the signaling proteins (p < 0.05). CONCLUSIONS: This suggests that CP pretreatment down-regulates LPS-mediated inflammation in lung epithelial cells. This study further confirmed that CP is a potential anti-inflammatory drug for the treatment of airway inflammatory diseases.

Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. METHODS: EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. RESULTS: Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-ß1 release. Blocking TGF-ß pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-ß1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-ß1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. CONCLUSIONS AND GENERAL SIGNIFICANCE: Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer.

Effectiveness of dry needling for myofascial trigger points associated with neck and shoulder pain: a systematic review and meta-analysis.

OBJECTIVE: To evaluate current evidence of the effectiveness of dry needling of myofascial trigger points (MTrPs) associated with neck and shoulder pain. DATA SOURCES: PubMed, EBSCO, Physiotherapy Evidence Database, ScienceDirect, The Cochrane Library, ClinicalKey, Wanfang Data Chinese database, China Knowledge Resource Integrated Database, Chinese Chongqing VIP Information, and SpringerLink databases were searched from database inception to January 2014. STUDY SELECTION: Randomized controlled trials were performed to determine whether dry needling was used as the main treatment and whether pain intensity was included as an outcome. Participants were diagnosed with MTrPs associated with neck and shoulder pain. DATA EXTRACTION: Two reviewers independently screened the articles, scored methodological quality, and extracted data. The results of the study of pain intensity were extracted in the form of mean and SD data. Twenty randomized controlled trials involving 839 patients were identified for meta-analysis. DATA SYNTHESIS: Meta-analyses were performed using RevMan version 5.2 and Stata version 12.0. The results suggested that compared with control/sham, dry needling of MTrPs was effective in the short term (immediately to 3 days) (standardized mean difference [SMD]=-1.91; 95% confidence interval [CI], -3.10 to -.73; P=.002) and medium term (SMD=-1.07; 95% CI, -1.87 to -.27; P=.009); however, wet needling (including lidocaine) was superior to dry needling in relieving MTrP pain in the medium term (SMD=1.69; 95% CI, .40-2.98; P=.01). Other therapies (including physiotherapy) were more effective than dry needling in treating MTrP pain in the medium term (9-28d) (SMD=.62; 95% CI, .02-1.21; P=.04). CONCLUSIONS: Dry needling can be recommended for relieving MTrP pain in neck and shoulders in the short and medium term, but wet needling is found to be more effective than dry needling in relieving MTrP pain in neck and shoulders in the medium term.