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Objective: The purpose of this study was to compare thermal desorption tubes and stainless steel canisters for measuring volatile organic compounds (VOCs) emitted from petrochemical factories. Methods: Twelve petrochemical factories in the Mailiao Industrial Complex were recruited for conducting the measurements of VOCs. Thermal desorption tubes and 6-l specially prepared stainless steel canisters were used to simultaneously perform active sampling of environmental air samples. The sampling time of the environmental air samples was set up on 6 h close to a full work shift of the workers. A total of 94 pairwise air samples were collected by using the thermal adsorption tubes and stainless steel canisters in these 12 factories in the petrochemical industrial complex. To maximize the number of comparative data points, all the measurements from all the factories in different sampling times were lumped together to perform a linear regression analysis for each selected VOC. Pearson product-moment correlation coefficient was used to examine the correlation between the pairwise measurements of these two sampling methods. A paired t-test was also performed to examine whether the difference in the concentrations of each selected VOC measured by the two methods was statistically significant. Results: The correlation coefficients of seven compounds, including acetone, n-hexane, benzene, toluene, 1,2-dichloroethane, 1,3-butadiene, and styrene were >0.80 indicating the two sampling methods for these VOCs' measurements had high consistency. The paired t-tests for the measurements of n-hexane, benzene, m/p-xylene, o-xylene, 1,2-dichloroethane, and 1,3-butadiene showed statistically significant difference (P-value < 0.05). This indicated that the two sampling methods had various degrees of systematic errors. Looking at the results of six chemicals and these systematic errors probably resulted from the differences of the detection limits in the two sampling methods for these VOCs. Conclusions: The comparison between the concentrations of each of the 10 selected VOCs measured by the two sampling methods indicted that the thermal desorption tubes provided high accuracy and precision measurements for acetone, benzene, and 1,3-butadiene. The accuracy and precision of using the thermal desorption tubes for measuring the VOCs can be improved due to new developments in sorbent materials, multi-sorbent designs, and thermal desorption instrumentation. More applications of thermal desorption tubes for measuring occupational and environmental hazardous agents can be anticipated. [ABSTRACT FROM AUTHOR]

Background: Irinotecan is approved and widely administered to metastatic colorectal cancer (mCRC) patients; however, it can cause severe toxicities including neutropenia and diarrhea. The polymorphisms of genes encoding drug-metabolizing enzymes can play a crucial role in the increased susceptibility of cancer patients to chemotherapy toxicity. Therefore, we plan to explore the effect of the genetic polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) for irinotecan detoxification in mCRC patients. This trial will compare the clinical outcomes and side effects observed in mCRC patients treated with bevacizumab plus 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with and without UGT1A1 genotyping and irinotecan dose escalation. A total of 400 mCRC patients were randomized into a study group and a control group.Methods/design: This trial is a prospective, multicenter, randomized clinical trial comparing UGT1A1 promoter polymorphism for irinotecan dose escalation in mCRC patients administered with bevacizumab plus FOLFIRI as the first-line setting. The enrolled patients were randomly assigned to one of two groups, a study group and a control group, on the basis of receiving UGT1A1 genotyping or not. The study group receive a biweekly FOLFIRI regimen, with irinotecan dose escalation based on UGT1A1 genotyping; whereas the control group receive the conventional biweekly FOLFIRI regimen without UGT1A1 genotyping. The clinicopathological features, response rates, toxicity, and progression-free survival or overall survival will be compared between the two groups.Discussion: Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan for a potentially more favorable clinical response and outcome, in addition to comparable toxicities. Such personalized medicine based on genotyping may be feasible for clinical practice.Trial Registration: NCT02256800 . Date of registration: 3 October 2014. Date of first patient randomized: 16 January 2015. [ABSTRACT FROM AUTHOR]

Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acidinduced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole-cell patch clamp recording to study the acid responsiveness and action potential (AP) configuration of capsaicin-sensitive neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size, resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and acid-induced current (Iacid), as well as capsaicin-induced current (Icap). TRPV1-expressing neurons were all acid-sensitive and could be divided into two acid-sensitive groups depending on an acid-induced sustained current (type I) or an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing neurons were distinguishable from type II TRPV1-expressing neurons in AP overshoot, after-hyperpolarization duration, and all Iacid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and Icap parameters. These differential biophysical properties of TRPV1-expressing neurons might partially annotate their different roles involved in the development and maintenance of chronic muscle pain. [ABSTRACT FROM AUTHOR]

Background. Inflammation is often considered to play a crucial role in epilepsy by affecting iron status andmetabolism. In this study, we investigated the curative effect of auricular acupuncture and somatic acupuncture on kainic acid- (KA-) induced epilepsy in rats. Methods.We established an epileptic seizure model in rats by KA (12mg, ip).The 2Hz electroacupuncture (EA) was applied at auricular and applied at Zusanli and Shangjuxu (ST36-ST37) acupoints for 20 min for 3 days/week for 6 weeks beginning on the day following theKAinjection. Results.The electrophysiological results indicated that neuron overexcitation occurred in theKA-treated rats.This phenomenon could be reversed among either the auricular EA or ST36-ST37 EA treatment, but not in the sham-control rats. The Western blot results revealed that TRPA1, but not TRPV4, was upregulated by injecting KA and could be attenuated by administering auricular or ST36-ST37 EA, but not in the sham group. In addition, potentiation of TRPA1 was accompanied by increased PKCα and reduced PKCε. Furthermore, pERK1/2, which is indicated in inflammation, was also increased by KA. Furthermore, the aforementioned mechanisms could be reversed by administering auricular EA and could be partially reversed by ST36-ST37 EA. Conclusions.These results indicate a novel mechanism for treating inflammation-associated epilepsy and can be translated into clinical therapy. [ABSTRACT FROM AUTHOR]

Human platelets express Toll-like receptors (TLR) 4. However, the mechanism by which TLR4 directly affects platelet aggregation and blood coagulation remains to be explored.Therefore, in this study, we evaluated the platelet TLR4 expression in patients who underwent CABG surgery; we explored the correlation between platelet TLR4 expression and the early outcomes in hospital of patients. Additionally, C57BL/6 and C57BL/6-TlrLPS-/- mice were used to explore the roles of platelet TLR4 in coagulation by platelet aggregometry and rotation thromboelastometry. In conclusion, our results highlight the important roles of TLR4 in blood coagulation and platelet function. Of clinical relevance, we also explored novel roles for platelet TLR4 that are associated with early outcomes in cardiac surgery. [ABSTRACT FROM AUTHOR]

Our previous study showed that mossy fiber sprouting can occur in the hippocampus region in rats 6wk after kainic acid-induced epileptic seizure, and this mossy fiber sprouting can facilitate epileptogenesis. Transcutaneous auricular vagal nerve stimulation (VNS), which is similar to cervical VNS, can reduce the occurrence of epileptic seizure in intractable epilepsy patients. Greater parasympathetic nerve activity can be caused by 2Hz electroacupuncture (EA). Therefore, we investigated the effect of 2Hz EA at ST-36-ST37 and at the ear on mossy fiber sprouting in kainic-treated Sprague-Dawley rats. The results indicated that applying 2Hz EA at ST36-ST37 and at the ear for 3 d per week over 6 consecutive weeks can amelioratemossy fiber sprouting in the hippocampus region of rats. These results indicated that applying 2Hz EA at ST36-ST37 and at the ear might be beneficial for the treatment and prevention of epilepsy in humans. [ABSTRACT FROM AUTHOR]

The expression of vascular adhesion molecule-1 (VCAM-1) by endothelial cells may play a major role in atherogenesis. The actual mechanisms of chlamydia pneumoniae (C. pneumoniae) relate to atherogenesis are unclear. We investigate the influence of VCAM-1 expression in the GroEL1 from C. pneumoniae-administered human coronary artery endothelial cells (HCAECs) and hypercholesterolemic rabbits. In this study, we constructed the recombinant GroEL1 from C. pneumoniae. The HCAECs/THP-1 adhesion assay, tube formation assay, western blotting, enzyme-linked immunosorbent assay, actinomycin D chase experiment, luciferase reporter assay, and immunohistochemical stainings were performed. The results show that GroEL1 increased both VCAM-1 expression and THP-1 cell adhesives, and impaired tube-formation capacity in the HCAECs. GroEL1 significantly increased the VCAM-1 mRNA stability and cytosolic AU-binding factor 1 (AUF1) level. Overexpression of the p37AUF1 significantly increased VCAM-1 gene expression in GroEL1-induced bovine aortic endothelial cells (BAECs). GroEL1 prolonged the stability of VCAM-1 mRNA by increasing both p37AUF1 and the regulation of the 59 untranslated region (UTR) of the VCAM-1 mRNA in BAECs. In hypercholesterolemic rabbits, GroEL1 administration enhanced fatty-streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated VCAM-1 expression. In conclusion, GroEL1 induces VCAM-1 expression by p37AUF1 in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits. [ABSTRACT FROM AUTHOR]

Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pHdependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pHdependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus. [ABSTRACT FROM AUTHOR]

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization. [ABSTRACT FROM AUTHOR]

Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33-41), 13 (F214-222), 14 (F273-281), and 23 (F559-567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-c and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice preimmunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine. [ABSTRACT FROM AUTHOR]

Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) plays a major role in oxidized low-density lipoprotein-induced vascular inflammation. Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis, although its specific mechanism remains unknown. This study was conducted to investigate the mechanisms of LOX-1 expression in GroEL1 (a heat shock protein from C. pneumoniae)-administered human coronary artery endothelial cells (HCAECs) and atherogenesis in hypercholesterolemic rabbits. We demonstrated that in the hypercholesterolemic rabbit model, GroEL1 administration enhanced fatty streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated LOX-1 expression. In in vitro study using HCAECs, stimulation with GroEL1 increased TLR4 and LOX-1 expression. Increased LOX-1 expression was downregulated by Akt activation and PI3K-mediated endothelial NO synthase activation. PI3K inhibitor and NO synthase inhibitor induced LOX-1 mRNA production, whereas the NO donor ameliorated the increasing effect of LOX-1 mRNA in GroEL1-stimulated HCAECs. LOX-1 expression was regulated by NADPH oxidase, which mediates reactive oxygen species production and intracellular MAPK signaling pathway in GroEL1-stimulated HCAECs. Treatment with polyethylene-glycol-conjugated superoxide dismutase, apocynin, or diphenylene iodonium significantly decreased GroEL1-induced LOX-1 expression, as did the knockdown of Rac1 gene expression by RNA interference. In conclusion, the GroEL1 protein may induce LOX-1 expression in endothelial cells and atherogenesis in hypercholesterolemic rabbits. The elevated level of LOX-1 in vitro may be mediated by the PI3K-Akt signaling pathway, endothelial NO synthase activation, NADPH oxidase-mediated reactive oxygen species production, and MAPK activation in GroEL1-stimulated HCAECs. The GroEL1 protein of C. pneumoniae may contribute to vascular inflammation and cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Background: Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus capable of transforming target cells in vitro and in vivo. The Envelope (Env) gene from JSRV and from related retroviruses can induce oncogenic transformation, although the detailed mechanism is yet to be clearly understood. Host cell factors are envisaged to play a critical determining role in the regulation of Env-mediated cell transformation. Results: JSRV Env-mediated transformation of a lung adenocarcinoma cell line induced rapid proliferation, anchorage-independent growth and tumor formation, but completely abrogated the migration ability. An analysis of the signaling scenario in the transformed cells suggested the involvement of the ERK pathway regulated by Sprouty2 in cell migration, and the PI3K-Akt and STAT3 pathways in proliferation and anchorage-independence. On the other hand, in a normal lung epithelial cell line, Env-mediated transformation only decreased the migration potential while the other functions remained unaltered. We observed that Env induced the expression of a tumor suppressor, Sprouty2, suggesting a correlation between Env-effect and Sprouty2 expression. Overexpression of Sprouty2 per se not only decreased the migratory potential and tumor formation potential of the target cells but also made them resistant to subsequent Env-mediated transformation. On the other hand, over expression of the functional mutants of Sprouty2 had no inhibitory effect, confirming the role of Sprouty2 as a tumor suppressor. Conclusions: Our studies demonstrate that Env and Sprouty2 have a functional relationship, probably through shared signaling network. Sprouty2 functions as a tumor suppressor regulating oncogenic transformation of cells, and it therefore has the potential to be exploited as a therapeutic anti-cancer agent. [ABSTRACT FROM AUTHOR]

Background: While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface. Methodology/Principal Findings: To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells. Conclusions/Significance: These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of β-adrenergic receptors in modulating associative long-term depression (LTD) at CA1 synapses in rat hippocampal slices. Standard extracellular electrophysiological techniques were employed to record field excitatory post-synaptic potential (fEPSP) activity and to induce associative LTD. Two independent Schaffer collateral pathways were elicited in hippocampal CA1 areas. In one (weak) pathway, the stimulating intensity was adjusted to elicit small fEPSP activity (20–30% of the maximum response). In contrast, 80–90% of the maximum response was evoked in the other (strong) pathway. Associative LTD of weak pathway could be induced by paired stimulation of weak and the strong pathways, repeated 100 times at 0.167 Hz. The associative LTD of weak pathway was NMDA receptor- and phophatase 2B dependent, because bath application of 50 µM D, L-AP5 or 10 µM cypermethrin blocked its induction. Bath application of 1 µM isoproterenol inhibited associative LTD, and this effect was blocked by timolol, suggesting the involvement of β-adrenergic receptors. The inhibitory effect of β-adrenergic receptors on LTD induction was blocked in slices pretreated with inhibitors of protein kinase A and mitogen-activated protein kinase, suggesting that these signal cascades are downstream effectors following activation of β-adrenergic receptors. Nevertheless, bath application of timolol or cypermethrin alone did not have significant effect on associative LTD induction, suggesting neither endogenous function of β-adrenergic receptor nor endogenous PKA activity does have a role in associative LTD induction. [ABSTRACT FROM AUTHOR]

Background: Experimentally verified protein-protein interactions (PPI) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be made faster by ranking newly-published articles' relevance to PPI, a task which we approach here by designing a machine-learning-based PPI classifier. All classifiers require labeled data, and the more labeled data available, the more reliable they become. Although many PPI databases with large numbers of labeled articles are available, incorporating these databases into the base training data may actually reduce classification performance since the supplementary databases may not annotate exactly the same PPI types as the base training data. Our first goal in this paper is to find a method of selecting likely positive data from such supplementary databases. Only extracting likely positive data, however, will bias the classification model unless sufficient negative data is also added. Unfortunately, negative data is very hard to obtain because there are no resources that compile such information. Therefore, our second aim is to select such negative data from unlabeled PubMed data. Thirdly, we explore how to exploit these likely positive and negative data. And lastly, we look at the somewhat unrelated question of which term-weighting scheme is most effective for identifying PPI-related articles. Results: To evaluate the performance of our PPI text classifier, we conducted experiments based on the BioCreAtIvEII IAS dataset. Our results show that adding likely-labeled data generally increases AUC by 3∼6%, indicating better ranking ability. Our experiments also show that our newly-proposed term-weighting scheme has the highest AUC among all common weighting schemes. Our final model achieves an F-measure and AUC 2.9% and 5.0% higher than those of the top-ranking system in the IAS challenge. Conclusion: Our experiments demonstrate the effectiveness of integrating unlabeled and likely labeled data to augment a PPI text classification system. Our mixed model is suitable for ranking purposes whereas our hierarchical model is better for filtering. In addition, our results indicate that supervised weighting schemes outperform unsupervised ones. Our newly-proposed weighting scheme, TFBRF, which considers documents that do not contain the target word, avoids some of the biases found in traditional weighting schemes. Our experiment results show TFBRF to be the most effective among several other top weighting schemes. [ABSTRACT FROM AUTHOR]

The preparation of porous copper or copper-zinc surfaces by electrochemical formation of binary Cu-Zn alloys on Cu substrate and subsequent electrochemical etching of the zinc was investigated in a zinc chloride-I-ethyl-3-methylimidazolium chloride ionic liquid at 120°C. Cyclic voltammetry and X-ray diffraction measurements suggested that phase transformation from γ- to β′- Cu-Zn alloy occurred during constant potential dealloying. Essentially all the Zn content in the Cu-Zn could be removed from the alloy with dealloying at a sufficiently positive potential. Dealloyed materials exhibited well-developed bicontinuous porous structure. The dependence of the surface morphology of the porous Cu film on several experimental parameters, including deposition current and charge, and anodizing potential and temperature, were examined. [ABSTRACT FROM AUTHOR]

Evaluates the role of β-adrenergic receptors in modulating associative long-term potentiation (LTP) induced at CA1 synapses. Description and function of LTP; Factors required for LTP induction; Kinases involved in the enhancement of the associative LTP.

Background: Microbial colonization on barrier materials used in guided tissue regeneration (GTR) may adversely affect treatment outcomes. The purposes of this study were: 1) to compare the invasion of Streptococcus mutans and Actinobacillus actinomycetemcomitans through 3 GTR membranes, composed of expanded polytetrafluoroethylene (ePTFE; non-resorbable), a glycolide fiber composite, and type 1 collagen (both bioabsorbable). and 2) to explore the effects of bacteria on the attachment of periodontal ligament (PDL) fibroblasts onto these membranes. Methods: Bacterial permeability was analyzed using a tube capped with a GTR membrane as a septum and filled with media. The tube was then placed in a bigger tube inoculated with S. mutans or A. actinomycetemcomitans. The passage of bacteria through the membranes into the inner tube was monitored. For cellular attachment experiments, primary human PDL cells were placed onto the GTR membranes with or without bacteria Attached cells were analyzed by scanning electron microscopy (SEM) analysis. Results: The ePTFE membrane had the best barrier effects followed by the collagen membrane and then the glycolide fiber composite membrane. Moreover. S. mutans passed through these membranes faster than A. actinomycetemcomitans. The attachment of PDL cells on the 3 membranes was also varied. The ePTFE membrane was the worst substrate for PDL fibroblast attachment. Moreover, both bacteria influenced the cellular attachment on the GTR membranes. Conclusions: Differences in the behavior of 3 GTR membranes penetrated by S mutans and A. actinomycetemcomitans were demonstrated. The results suggest that attachment of PDL cells was affected on bacterial-contaminated GTR membranes, which may alter healing following membrane exposure. [ABSTRACT FROM AUTHOR]

Objective(s): Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model. Materials and Methods: We injected thrice complete Freund’s adjuvant (CFA) into the mouse’s hind paw to induce CIP. Results: We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1. Conclusion: These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain. [ABSTRACT FROM AUTHOR]

Background. Cardiopulmonary bypass (CPB) causes release of matrix metalloproteinase- (MMP-) 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation followingCPB.Methods. Thirty patients undergoing elective cardiac surgerywere included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB) for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. Results.The plasma MMP-9 concentrations significantly elevated at 2–6 h after beginning CPB (𝑃 < 0.001) and returned to the preanesthesia level at 24 h (𝑃 = 0.23), with predominant neutrophil counts after surgery (𝑃 < 0.001). The plasma MMP-9 levels at 4 and 6 h were not correlatedwith prolongedCPB time and displayed no associationwith postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9 ± 81.2 to postoperative 207.3 ± 121.3mmHg (𝑃 < 0.001). Conclusion. Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation. [ABSTRACT FROM AUTHOR]

Objective(s): Fibromyalgia pain is a mysterious clinical pain syndrome, characterized by inflammation in the brain, whose molecular mechanisms are still unknown. Females are more commonly affected by fibromyalgia, exhibiting symptoms such as widespread mechanical pain, immune dysfunction, sleep disturbances, and poor quality of life. Electroacupuncture (EA) has been used to relieve several types of pain, including fibromyalgia pain. Materials and Methods: In the present study, we used dual injections of acidic saline into the gastrocnemius muscle to initiate a neural activation that resulted in fibromyalgia pain in mice. We used the Von Frey test to measure mechanical hyperalgesia and Western blot to measure protein levels. Results: Results indicated that mechanical hyperalgesia can be induced in mice for 4 weeks, suggesting the induction of chronic fibromyalgia (CFM). Furthermore, continuous EA treatment reliably attenuated the mechanical hyperalgesia, but not in the sham control group. Results also suggested that the mechanical hyperalgesia can be prevented in mice with TRPV1 gene deletion. Mice with CFM showed increased expressions ofTRPV1, Nav1.7, andNav1.8 in the dorsal root ganglion (DRG) and the spinal cord (SC). The expression of TRPV1-associated molecules such as pPKA, pERK, and pCREB was also increased in the thalamus and somatosensory cortex (SSC) of the mice. All the aforementioned mechanisms were reversed by EA treatment and TRPV1 gene deletion. Conclusion: Altogether, our results implied significant mechanisms of CFM and EA-analgesia that involve the regulation of the TRPV1 signaling pathway. These findings may be relevant to the evaluation and treatment of CFM. [ABSTRACT FROM AUTHOR]

The article discusses the neurotransmitter called substance P that reduces acid-induced chronic muscles pain. It states that substance P is a small protein generated in pain receptor neurons and released in response to painful stimulation. It mentions that substance P reduces the acid-induced inward current in acid-sensing ion channel 3 (ASIC3) expressing muscle nociceptors, but not in other sensory neurons.

Objective(s): Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain. Materials and Methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint. Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1-/- groups. Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND The role of the Y chromosome-encoded Deleted in Azoospermia (DAZ) gene family in spermatogenesis remains unclear. The ability of men without the DAZ gene to produce sperm, as well as the lack of selective pressure on DAZ exon sequences during evolution, casts doubts on its functional significance. Most men have four DAZ genes encoding protein isoforms that differ significantly in size. However, published western blots showed only a single “DAZ” band, raising the possibility that not all four DAZ genes are expressed. METHODS RT–PCR, western blotting and immunostaining were used to study the expression of the four DAZ genes and the autosomal DAZL gene in human testes and in tissue culture cells. RESULTS RNA transcripts of all four DAZ genes were found in the testis, but at much lower levels than that of the DAZL transcripts. Expression in cultured somatic cells showed that DAZ transcripts encoding multiple DAZ repeats were translated inefficiently. No DAZ proteins could be unambiguously identified on western blots when the testicular samples from three patients without the DAZ genes were used as negative controls. Nonetheless, low levels of DAZ were detected in the cytoplasm of spermatogonia by immunostaining. CONCLUSIONS The expression of DAZ proteins in adult human testes is restricted to the spermatogonia and suggests a premeiotic role. [ABSTRACT FROM AUTHOR]

Objective(s): Parkinson’s disease (PD) is a common progressive neurodegeneration disease. Its incidence increases with age and affects about 1% of people over 60. Incidentally, transient receptor potential V1 (TRPV1) and its relation with neuroinflammation in mouse brain has been widely reported. Materials and Methods: We used 6-hydroxydopamine (6-OHDA) to induce PDD in mice. We then used the Morris water maze and Bio-Plex to test learning and inflammatory mediators in mouse plasma. Western blotting and immunostaining were used to examine TRPV1 pathway in the hippocampus and medial prefrontal cortex (mPFC). Results: On acquisition days 3 (Control = 4.40 ± 0.8 sec, PDD = 9.82 ± 1.52 sec, EA = 5.04 ± 0.58 sec, Riva = 4.75 ± 0.87 sec; P=0.001) and 4, reversal learning days 1, 2, 3 (Control = 2.86 ± 0.46 sec, PDD = 9.80 ± 1.83 sec, EA = 4.6 ± 0.82 sec, Riva = 4.6 ± 1.03 sec; P=0.001) and 4, PDD mice showed significantly longer escape latency than the other three groups. Results showed that several cytokines were up-regulated in PDD mice and reversed by EA and rivastigmine. TRPV1 and downstream molecules were up-regulated in PDD mice and further reversed by EA and rivastigmine. Interestingly, α7 nicotinic receptors and parvalbumin levels in both the hippocampus and prefrontal cortex increased in EA-treated mice, but not in rivastigmine-treated mice. Conclusion: Our results showed that TRPV1 played a role in the modulation of neuroinflammation of PDD, and could potentially be a new target for treatment. [ABSTRACT FROM AUTHOR]

Objective(s): Fibromyalgia (FM) is a central nervous system disorder characterized by widespread mechanical hyperalgesia due to unknown mechanisms. Several inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor, are increased in the serum of FM patients. Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying. In the present study we assessed whether electroacupuncture (EA) can reduce chronic FM pain and then proposed an underlying mechanism for this effect. Materials and Methods: Chronic FM pain was induced in mice by dual acid saline injection lasting up to 4 weeks. Results: Chronic FM pain was treated by EA manipulation, but not in the sham operated group. Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment. The pPI3K-associated nociceptive signaling pathway was increased in the thalamus of FM mice, but reversed by EA. Similar results were observed in the mouse somatosensory cortex. Conclusion: These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice. [ABSTRACT FROM AUTHOR]

Background/Aims: Acupuncture involves inserting a fine needle into a specific point, often called an acupoint, thereby initiating a therapeutic effect accompanied by phenomena such as soreness, heaviness, fullness, and numbness. Acupoints are characterized as points located in deep tissues with abundant sensory nerve terminals, which suggests that there is a strong relationship between acupoints and peripheral sensory afferents. In this study, we determined whether manual acupuncture (MA) or different frequencies of electroacupuncture (EA) share similar mechanisms for activating excitatory neurotransmission. Methods: We performed MA or EA at acupoint ST36 and we also used western blot and immunostaining techniques to determine neural changes at the peripheral dorsal root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels. Results: Our results show that either MA or EA at the ST36 acupoint significantly increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K, pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC-SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor (pNMDA) and pCaMKIIα (but not pNR2B, pCaMKIId, or pCaMKIIg) also increased. These molecules could not increase in the DRG and SC-SSC of TRPV1-/-mice. Conclusion: Our data demonstrates that both MA and EA can activate excitatory signals in either peripheral or central levels. We also define that TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1-pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies the real clinical significance. [ABSTRACT FROM AUTHOR]

The therapeutic effect in non-small cell lung cancer (NSCLC) patients is limited because of intrinsic and acquired resistance. Thus, an unmet need exists for the development of new drugs to improve the therapeutic efficacy in NSCLC patients. In this study, the novel small molecule indolizino[6,7-b]indole derivative BO-1978 was selected to evaluate its therapeutic effects on NSCLC and its preclinical toxicity in animal models. An in vitro cytotoxicity assay revealed that BO-1978 significantly suppressed the growth of various NSCLC cell lines with or without mutations in epidermal growth factor receptor (EGFR). Mechanistically, we demonstrated that BO-1978 exhibited multiple modes of action, including inhibition of topoisomerase I/II and induction of DNA cross-linking. Treatment of NSCLC cells with BO-1978 caused DNA damage, disturbed cell cycle progression, and triggered apoptotic cell death. Furthermore, BO-1978 significantly suppressed the growth of EGFR wild-type and mutant NSCLC tumors in xenograft tumor and orthotopic lung tumor models with negligible body weight loss. The combination of BO-1978 with gefitinib further suppressed EGFR mutant NSCLC cell growth in xenograft tumor and orthotopic lung tumor models. Preclinical toxicity studies showed that BO-1978 administration did not cause apparent toxicity in mice. Based on its significant therapeutic efficacy and low drug toxicity, BO-1978 is a potential therapeutic agent for treatment of NSCLC. [ABSTRACT FROM AUTHOR]