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Tomoya Hirose, Hiroshi Ogura, Hiroki Takahashi, Masahiro Ojima, Kang Jinkoo, Youhei Nakamura, Takashi Kojima, Takeshi Shimazu
Background: C1 inhibitor (C1-INH), which belongs to the superfamily of serine protease inhibitors, regulates the complement system and also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1-INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective of this study was to clarify the serial change of C1-INH in patients with sepsis and evaluate the relationship with the shock severity. Methods: This was a single-center, prospective, observational study...
2018: Journal of Intensive Care
Frederick Wasinski, Rogerio Oliveira Batista, Michael Bader, Ronaldo C Araujo, Friederike Klempin
Physical exercise is a strong external effector that induces precursor cell proliferation in the adult mouse hippocampus. Research into mechanisms has focused on central changes within the hippocampus and we have established that serotonin is the signaling factor that transduces physical activity into adult neurogenesis. Less focus has been given on potential peripheral signals that may cause pro-mitotic running effects. Vasoactive kinin peptides are important for blood pressure regulation and inflammatory processes to maintain cardiovascular homeostasis...
July 9, 2018: Brain Structure & Function
Miki Akasaka, Kazuhiro Osato, Mito Sakamoto, Tomohisa Kihira, Tomoaki Ikeda, Takaharu Yamawaki
Amniotic fluid embolism (AFE) causes consumption coagulopathy, which requires a massive transfusion to save the mother's life. The preparation of such a massive transfusion is too time-consuming in extremely emergent clinical settings and occasionally leads to devastating side effects such as transfusion-associated acute lung injury. C1 esterase inhibitor (C1INH) is a protein with the ability to inhibit complement, coagulation and kinin pathways. The C1INH concentration in AFE patients is low, and it has been speculated that the administration of C1INH concentrate could have a striking and beneficial effect on AFE patients in critical condition by ameliorating their perturbed coagulation system...
July 5, 2018: Journal of Obstetrics and Gynaecology Research
Felipe J Cavichioli, Graylin N B Bernal, Iandra Holzmann, Juliana Bagatini Klein, Ricardo Escarcena, Esther Del Olmo, Arturo San Feliciano, Valdir Cechinel Filho, Nara L M Quintão
BACKGROUND: The study evaluated the effects of two sphingosine derivatives N-(2-tert-butoxycarbamylhexadecyl)glutaramide (AA) and N-(1-benzyloxyhexadec-2-yl)glutaramide (OA) in different models of hypersensitivity in mice. METHODS: Male Swiss mice were orally pre-treated with AA or OA (0.3-3 mg/kg). After 1 h, they received λ-carrageenan (300 μg/paw), lipopolysaccharide (LPS; 100 ng/paw), bradykinin (BK; 500 ng/paw) or prostaglandin E2 (PGE2 ; 0.1 nmol/paw) or epinephrine (100 ng/paw), and the mechanical withdrawal thresholds were evaluated using von Frey filament (0...
February 23, 2018: Pharmacological Reports: PR
Uriel Koziol
Tardigrades are a key group for understanding the evolution of the Ecdysozoa, a large clade of molting animals that also includes arthropods and nematodes. However, little is known about most aspects of their basic biology. Neuropeptide and peptide hormone signaling has been extensively studied in arthropods and nematodes (particularly regarding their roles in molting in arthropods), but very little is known about neuropeptide signaling in other ecdysozoans. In this work, different strategies were used to search for neuropeptide and peptide hormone precursors in the genomes of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus...
June 20, 2018: General and Comparative Endocrinology
Zhenyu Wei, Yi Lyu, XiaoLi Yang, Xin Chen, Ping Zhong, Danhong Wu
The term "tissue kallikrein" is used to describe a group of serine proteases shared considerable sequence homology and colocalize in the same chromosomal locus 19q13. 2-q13.4. It has been widely discovered in various tissues and has been proved to be involved in kinds of pathophysiological processes, such as inhibiting oxidative stress, inflammation, apoptosis, fibrosis and promoting angiogenesis, and neurogenesis. Human Urinary Kallidinogenase (HUK) extracted from human urine is a member of tissue kallikrein which could convert kininogen to kinin and hence improve the plasma kinin level...
2018: Frontiers in Neurology
Pedro F Malacarne, Thiago N Menezes, Cleciane W Martins, Gustavo B Naumann, Helena L Gomes, Rita G W Pires, Suely G Figueiredo, Fabiana V Campos
Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects. These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules. In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom...
June 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
Anthoula Chatzikyriakidou, Paraskevi V Voulgari, Alexandros A Drosos
Objectives: This study aims to examine the following functional polymorphisms in rheumatoid arthritis (RA) susceptibility: (i) the 587C>T of kininogen gene, (ii) the 287 bp Alu repeat insertion of angiotensin converting enzyme gene, (iii) the 9 bp insertion of bradykinin receptor 2 gene, (iv) the -58T>C of bradykinin receptor 2 gene, and (v) the -699G>C of bradykinin receptor 1 gene. Patients and methods: The study included 136 RA patients (27 males; 109 females; mean age 60...
March 2018: Archives of Rheumatology
Pamela Ehrenfeld, Kanti D Bhoola, Carola E Matus, Carlos D Figueroa
In the human neutrophil, kallikrein-related peptidases (KLKs) have a significant functional relationship with the classical kinin system since a kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium. Secretion of KLK1, the kinin-forming enzyme, may perpetuate formation of kinin in the inflammatory milieu by hydrolyzing extravasated kininogens present in tissue edema. Secretion of KLKs into the inflammatory milieu, induced by kinins or other proinflammatory mediators, provides the human neutrophil with a wide range of molecular interactions to hydrolyze different cellular and extracellular matrix components, which may be of critical relevance in different mechanisms involving inflammation...
December 20, 2017: Biological Chemistry
Henning Ulrich, Mariusz Z Ratajczak, Gabriela Schneider, Elena Adinolfi, Elisa Orioli, Enéas G Ferrazoli, Talita Glaser, Juliana Corrêa-Velloso, Poliana C M Martins, Fernanda Coutinho, Ana P J Santos, Micheli M Pillat, Ulrich Sack, Claudiana Lameu
Bone marrow metastasis occurs in approximately 350,000 patients that annually die in the U.S. alone. In view of the importance of tumor cell migration into the bone marrow, we have here investigated effects of various concentrations of stromal cell-derived factor-1 (SDF-1), bradykinin- and ATP on bone marrow metastasis. We show for first time that bradykinin augmented chemotactic responsiveness of neuroblastoma cells to SDF-1 and ATP concentrations, encountered under physiological conditions. Bradykinin upregulated VEGF expression, increased metalloproteinase activity and induced adhesion of neuroblastoma cells...
2018: Frontiers in Pharmacology
Muhammad Khalid, Majd Kanaa, Yazan Alkawaleet, Muhammad Talha Ayub
Angioedema is a localized, non-pitting, non-dependent, submucosal, and subcutaneous swelling resulting from the extravasation of fluid into the interstitium due to the increased production of plasma kinins and histamine. It can present with urticaria or anaphylaxis and is usually associated with angiotensin-converting enzyme inhibitors (ACEis), complement deficiencies, or the side effects of tissue plasminogen activator (tPA). Orolingual angioedema following tPA for acute ischemic stroke is a transient, self-resolving hemifacial swelling contralateral to neurological deficits that can rarely progress to the airway, compromising it and leading to a life-threatening situation if not managed promptly...
March 29, 2018: Curēus
Min Tang, Xia Li, Ping Liu, Jianwen Wang, Fangping He, Xiongchao Zhu
BACKGROUND: Kinins are pro-inflammatory peptides that mediate numerous vascular and pain responses in tissue injury. Kinins exert their biological functions via two G-protein-coupled receptors: bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R). We previously demonstrated the up-regulation of B2R after hypoxia/reoxygenation (H/R) injury in primary cultured cortical neurons. However, the role of B2R in inflammasome-induced pyroptosis remains unknown. METHODS: We induced H/R neuronal injury in primary cultured cortical neurons harvested from embryonic day 17 brains...
May 27, 2018: Current Neurovascular Research
François Marceau, Marie-Thérèse Bawolak, Jean-Philippe Fortin, Guillaume Morissette, Caroline Roy, Hélène Bachelard, Lajos Gera, Xavier Charest-Morin
Kinins are the small and fragile hydrophilic peptides related to bradykinin (BK) and derived from circulating kininogens via the action of kallikreins. Kinins bind to the preformed and widely distributed B2 receptor (B2 R) and to the inducible B1 receptor (B1 R). B2 Rs and B1 Rs are related G protein coupled receptors that possess natural agonist ligands of nanomolar affinity (BK and Lys BK for B2 Rs, Lys-des-Arg9 -BK for B1 R). Decades of structure-activity exploration have resulted in the production of peptide analogs that are antagonists, one of which is clinically used (the B2 R antagonist icatibant), and also non-peptide ligands for both receptor subtypes...
July 2018: Peptides
Günnur Koçer, Filiz Basralı, Oktay Kuru, Ümit Kemal Şentürk
BACKGROUND/AIMS: Temporary proteinuria post-exercise is common and is caused predominantly by renal haemodynamic alterations. One reason is up-regulation of angiotensin II (Ang II) due to the reducing effect of angiotensin-converting enzyme (ACE) inhibitors. However, another, ignored, reason could be the kininase effect of ACE inhibition. This study investigated how ACE inhibition reduces post-exercise proteinuria: by either Ang II up-regulation inhibition or bradykinin elevation due to kininase activity inhibition...
May 17, 2018: Nephron
Kritika Ramani, Chetan V Jawale, Akash H Verma, Bianca M Coleman, Jay K Kolls, Partha S Biswas
Kidney injury is a frequent outcome in patients with disseminated Candida albicans fungal infections. IL-17 receptor (IL-17R) signaling is critical for renal protection against disseminated candidiasis, but the identity and function of IL-17-responsive cells in mediating renal defense remains an active area of debate. Using BM chimeras, we found that IL-17R signaling is required only in nonhematopoietic cells for immunity to systemic C. albicans infection. Since renal tubular epithelial cells (RTEC) are highly responsive to IL-17 in vitro, we hypothesized that RTEC might be the dominant target of IL-17 activity in the infected kidney...
May 3, 2018: JCI Insight
Sander Liessem, Lapo Ragionieri, Susanne Neupert, Ansgar Büschges, Reinhard Predel
One of the most thoroughly studied insect species, with respect to locomotion behavior, is the stick insect Carausius morosus. Although detailed information exists on premotor networks controlling walking, surprisingly little is known about neuropeptides, which are certainly involved in motor activity generation and modulation. So far, only few neuropeptides were identified from C. morosus or related stick insects. We performed a transcriptome analysis of the central nervous system to assemble and identify 65 neuropeptide and protein hormone precursors of C...
June 1, 2018: Journal of Proteome Research
Adrian Leontovyč, Lenka Ulrychová, Anthony J O'Donoghue, Jiří Vondrášek, Lucie Marešová, Martin Hubálek, Pavla Fajtová, Marta Chanová, Zhenze Jiang, Charles S Craik, Conor R Caffrey, Michael Mareš, Jan Dvořák, Martin Horn
BACKGROUND: Serine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat (TSR-1). These proteases are recognized as antigens during host infection and may prove useful as anthelminthic vaccines, however their molecular characteristics are under-studied. Here, we characterize the structural and proteolytic attributes of serine protease 2 (SmSP2) from Schistosoma mansoni, one of the major species responsible for the tropical infectious disease, schistosomiasis...
April 2018: PLoS Neglected Tropical Diseases
Hélène Bachelard, Xavier Charest-Morin, François Marceau
We previously reported hypotensive and vasodilator effects from C-terminally extended bradykinin (BK) sequences that behave as B2 receptor (B2 R) agonists activated by vascular or plasma peptidases. D-Arg0 -BK-Arg-Arg (r-BK-RR) is a novel prodrug peptide hypothetically activated by two catalytic cycles of Arg-carboxypeptidases (CPs) to release the direct agonist D-Arg0 -BK. N-terminally extending the BK sequence with D-Arg0 in the latter peptide was meant to block the second kinin inactivation pathway in importance, aminopeptidase P...
2018: Frontiers in Pharmacology
Min Chul Cho, Won Hoon Song, Jae-Seung Paick
INTRODUCTION: Cavernosal fibrosis is an important pathologic condition leading to erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, diabetes mellitus, castration, cavernosal nerve injury during radical prostatectomy, hypertension, and Peyronie disease. AIMS: To summarize published studies investigating suppression of cavernosal fibrosis in rat models of ED of various etiologies. METHODS: A literature search was conducted using PubMed...
April 6, 2018: Sexual Medicine Reviews
Patricia Luiza Nunes da Costa, David Wynne, Theodora Fifis, Linh Nguyen, Marcos Perini, Christopher Christophi
BACKGROUND: The Kallikrein-Kinin System (KKS) has been found to play a role in tumor progression in several cancers. The KKS metabolic cascade depends on signalling through two cross talking receptors; bradykinin receptor 1 (B1R) and bradykinin receptor 2 (B2R). Activation of the Kinin receptor is responsible for multiple pathophysiologic functions including increase of vascular permeability and induction of host inflammatory responses that exert diverse effects on tumor growth. METHODS: B1R and B2R expression on mouse and human CRC cell lines was investigated...
April 4, 2018: BMC Cancer
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