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https://www.readbyqxmd.com/read/28231522/novel-2-3-disubstituted-quinazoline-4-3h-one-molecules-derived-from-amino-acid-linked-sulphonamide-as-a-potent-malarial-antifolates-for-dhfr-inhibition
#1
Tarosh S Patel, Satish F Vanparia, Urmila H Patel, Ritu B Dixit, Chaitanya J Chudasama, Bhavesh D Patel, Bharat C Dixit
An optimization of a modified Grimmel's method for N-heterocyclization of Leucine linked sulphonamide leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, nineteen hybrid quinazolinone motifs (5a-5s) were synthesized by N-heterocyclization reaction under microwave irradiation using TEAA (IL) as green solvent as well as catalyst. The in vitro screening of the hybrid entities against the plasmodium species P. falciparum yielded five antimalarial potent molecules 5g, 5l, 5m, 5n &5p owing comparable activity to the reference drugs...
February 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28229304/early-elevated-levels-of-soluble-triggering-receptor-expressed-on-myeloid-cells-1-in-subarachnoid-hemorrhage-patients
#2
Xin-Gang Sun, Qian Ma, Gang Jing, Li Wang, Xu-Dong Hao, Gai-Qing Wang
Early brain injury (EBI) contributes to poor prognosis of subarachnoid hemorrhage (SAH). This study aimed to clarify whether triggering receptor expressed on myeloid cells-1 (TREM-1) was implicated in the inflammatory mechanisms of EBI. The cerebrospinal fluid (CSF) levels of soluble TREM-1 (sTREM-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as plasma levels of white blood cells (WBC) count and C-reactive protein in 17 SAH patients at early stage (within the EBI period) and 9 volunteers were observed...
February 22, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28229280/posterior-urethral-valve-in-fetuses-evidence-for-the-role-of-inflammatory-molecules
#3
Érica Leandro Marciano Vieira, Natalia Pessoa Rocha, Fernando Macedo Bastos, Kátia Daniela da Silveira, Alamanda K Pereira, Eduardo Araújo Oliveira, Débora Marques de Miranda, Ana Cristina Simões E Silva
BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]...
February 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28229025/effect-of-interleukin-il-35-on-il-17-expression-and-production-by-human-cd4-%C3%A2-t-cells
#4
Kosuke Okada, Takeki Fujimura, Takeshi Kikuchi, Makoto Aino, Yosuke Kamiya, Ario Izawa, Yuki Iwamura, Hisashi Goto, Iichiro Okabe, Eriko Miyake, Yoshiaki Hasegawa, Makio Mogi, Akio Mitani
BACKGROUND: Interleukin (IL)-17 produced by mainly T helper 17 (Th17) cells may play an important destructive role in chronic periodontitis (CP). Thus, anti-inflammatory cytokines, such as IL-35, might have a beneficial effect in periodontitis by inhibiting differentiation of Th17 cells. Th17 differentiation is regulated by the retinoic acid receptor-related orphan receptor (ROR) α (encoded by RORA) and RORγt (encoded by RORC). However, the role of IL-35 in periodontitis is not clear and the effect of IL-35 on the function of Th17 cells is still incompletely understood...
2017: PeerJ
https://www.readbyqxmd.com/read/28228560/expression-of-il-22-in-the-skin-causes-th2-biased-immunity-epidermal-barrier-dysfunction-and-pruritus-via-stimulating-epithelial-th2-cytokines-and-the-grp-pathway
#5
Hongfei Lou, Jingning Lu, Eun Byul Choi, Min Hee Oh, Mingeum Jeong, Sara Barmettler, Zhou Zhu, Tao Zheng
Increased expression of Th22 cytokine IL-22 is a characteristic finding in atopic dermatitis (AD). However, the specific role of IL-22 in the pathogenesis of AD in vivo has yet to be elucidated. Consistent with observations in human AD, IL-22 was significantly increased in the AD skin of mice after epicutaneous sensitization to house dust mite allergen. Utilizing a skin-specific inducible transgenic system, we show in the present study that expression of IL-22 in the skin of mice caused an AD-like phenotype characterized by chronic pruritic dermatitis associated with Th2-biased local and systemic immune responses, downregulation of epidermal differentiation complex genes, and enhanced dermatitis upon epicutaneous allergen exposure...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28226203/characteristic-changes-in-decidual-gene-expression-signature-in-spontaneous-term-parturition
#6
Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G Price, Zhong Dong, Adi L Tarca, Zoltan Papp, Sonia S Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than
Background: The decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process...
February 22, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28225489/immunoregulation-effects-of-different-%C3%AE-%C3%AE-t-cells-and-toll-like-receptor-signaling-pathways-in-neonatal-necrotizing-enterocolitis
#7
Lei Hui, Yi Dai, Zhi Guo, Jiahui Zhang, Fang Zheng, Xiangli Bian, Zhimin Wu, Qin Jiang, Miaomiao Guo, Ke Ma, Jinping Zhang
The aim of the study was to observe cytokine and T-cell-related toll-like-receptor (TLR) changes in intestinal samples of neonatal necrotizing enterocolitis patients.Four necrotic bowels were collected from neonatal NEC patients with gestational ages of 28 to 29 weeks in our hospital, whereas 4 neonatal patients who underwent intestinal atresia surgery served as the controls. Intestinal flora was examined and IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and IL-17 expressions in resected intestine samples, as well as in isolated gamma delta T (γδT) cells, were analyzed immunohistochemically and via quantitative RT-PCR...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28225209/association-of-the-il-10-receptor-a536g-s138g-loss-of-function-variant-with-multiple-sclerosis-in-tunisian-patients
#8
Nadia Ben Fredj, Mouna Aissi, Walid Ben Selma, Imen Mahmoud, Faten Nefzi, Mahbouba Frih-Ayed, Jalel Boukadida, Mahjoub Aouni
Interleukin-10 (IL-10), a potent anti-inflammatory T-cell cytokine, has been shown to be a regulatory cytokine that is associated with disease remission in multiple sclerosis (MS) and exerts its activity through its cognate cell surface receptor complex, IL-10 receptor 1 (IL-10R1) and IL-10R2. The purpose of this study was to investigate the IL-10R1 S138G loss-of-function polymorphism (A536G: rs3135932) for possible influence on susceptibility and outcome of MS in Tunisian patients. A total of 103 Tunisian MS patients and 160 control subjects were studied...
February 22, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28224996/intelectin-contributes-to-allergen-induced-il-25-il-33-and-tslp-expression-and-type-2-response-in-asthma-and-atopic-dermatitis
#9
L Yi, D Cheng, K Zhang, X Huo, Y Mo, H Shi, H Di, Y Zou, H Zhang, J Zhao, Y Xu, D J Erle, G Zhen
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness...
February 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#10
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28223794/airway-gene-expression-of-il-1-pathway-mediators-predicts-exacerbation-risk-in-obstructive-airway-disease
#11
Katherine J Baines, Juan-Juan Fu, Vanessa M McDonald, Peter G Gibson
BACKGROUND: Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. METHODS: In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#12
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223539/thymol-mitigates-lipopolysaccharide-induced-endometritis-by-regulating-the-tlr4-and-ros-mediated-nf-%C3%AE%C2%BAb-signaling-pathways
#13
Haichong Wu, Kangfeng Jiang, Nannan Yin, Xiaofei Ma, Gan Zhao, Changwei Qiu, Ganzhen Deng
The purpose of this study was to investigate the effects of thymol on lipopolysaccharide (LPS)-induced inflammatory responses and to clarify the potential mechanism of these effects. LPS-induced mouse endometritis was used to confirm the anti-inflammatory action of thymol in vivo. RAW264.7 cells were used to examine the molecular mechanism and targets of thymol in vitro. In vivo, thymol markedly alleviated LPS-induced pathological injury, myeloperoxidase (MPO) activity, and the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28222752/dendritic-cells-macrophages-nk-and-cd8-t-lymphocytes-play-pivotal-roles-in-controlling-hsv-1-in-the-trigeminal-ganglia-by-producing-il1-beta-inos-and-granzyme-b
#14
Natália Lucinda, Maria Marta Figueiredo, Natália Lima Pessoa, Beatriz Senra Álvares da Silva Santos, Graciela Kunrath Lima, Arthur Molinari Freitas, Alexandre Magalhães Vieira Machado, Erna Geessien Kroon, Lis Ribeiro do Valle Antonelli, Marco Antônio Campos
BACKGROUND: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1β) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1β production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28221365/glial-glt-1-blockade-in-infralimbic-cortex-as-a-new-strategy-to-evoke-rapid-antidepressant-like-effects-in-rats
#15
J Gasull-Camós, M Tarrés-Gatius, F Artigas, A Castañé
Ketamine and deep brain stimulation produce rapid antidepressant effects in humans and rodents. An increased AMPA receptor (AMPA-R) signaling in medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research has addressed the direct effects of enhancing glutamate tone or AMPA-R stimulation in mPFC subdivisions. The current study investigates the behavioral and neurochemical consequences of glutamate transporter-1 (GLT-1) blockade or s-AMPA microinfusion in the infralimbic (IL) and prelimbic (PrL) cortex...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28220116/cpg-odn-shapes-alum-adjuvant-activity-signaling-via-myd88-and-il-10
#16
Luciana Mirotti, Ricardo Wesley Alberca Custódio, Eliane Gomes, Florencia Rammauro, Eliseu Frank de Araujo, Vera Lucia Garcia Calich, Momtchilo Russo
Aluminum-containing adjuvants usually referred as Alum are considered as T helper type-2 (Th2) adjuvants, while agonists of toll-like receptors (TLRs) are viewed as adjuvants that favor Th1/Th17 immunity. Alum has been used in numerous vaccine formulations; however, its undesired pro-Th2 adjuvant activity constitutes a caveat for Alum-based vaccines. Combining Alum with TLR-dependent, pro-Th1/Th17 adjuvants might dampen the pro-Th2 activity and improve the effectiveness of vaccine formulations. Here, using the ovalbumin (OVA) model of allergic lung inflammation, we found that sensitization with the synthetic TLR9 agonist, which is composed of oligodeoxynucleotides containing CpG motifs adsorbed to Alum, inhibited the development of OVA-induced lung allergic Th2 responses without shifting toward a Th1 pattern...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219988/sex-differences-in-microglia-activity-within-the-periaqueductal-gray-of-the-rat-a-potential-mechanism-driving-the-dimorphic-effects-of-morphine
#17
H H Doyle, L N Eidson, D M Sinkiewicz, A Z Murphy
Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require 2-3 times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal μ opioid receptor (MOR), morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28219839/sinigrin-inhibits-production-of-inflammatory-mediators-by-suppressing-nf-%C3%AE%C2%BAb-mapk-pathways-or-nlrp3-inflammasome-activation-in-macrophages
#18
Hee-Weon Lee, Chung Gi Lee, Dong-Kwon Rhee, Sung Hee Um, Sukneung Pyo
Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome. In a concentration-dependent manner, sinigrin inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the expression of COX-2 and prostaglandin E2 (PGE2) in RAW 264...
February 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28219837/chronic-maternal-calcium-and-25-hydroxyvitamin-d-deficiency-in-wistar-rats-programs-abnormal-hepatic-gene-expression-leading-to-hepatic-steatosis-in-female-offspring
#19
Sona S Sharma, Nivedita M Jangale, Abhay M Harsulkar, Medha K Gokhale, Bimba N Joshi
Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation...
February 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28219835/marked-in-vivo-donor-treg-expansion-via-il-2-and-tl1a-ig-stimulation-ameliorates-gvhd-but-preserves-gvl-in-recipients-post-hsct
#20
Dietlinde Wolf, Henry Barreras, Cameron S Bader, Sabrina Copsel, Casey O Lightbourn, Brent J Pfeiffer, Norman H Altman, Eckhard R Podack, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are critical for self-tolerance. While adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen and colon (a GVHD target tissue)...
February 17, 2017: Biology of Blood and Marrow Transplantation
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