Read by QxMD icon Read


Berhane Ghebrehiwet, Allen P Kaplan, Kusumam Joseph, Ellinor I B Peerschke
The blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar "initiating trigger" followed by sequential and cascade-like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein-kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross-talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer...
November 2016: Immunological Reviews
Kristina N Ekdahl, Yuji Teramura, Osama A Hamad, Sana Asif, Claudia Duehrkop, Karin Fromell, Elisabet Gustafson, Jaan Hong, Huda Kozarcanin, Peetra U Magnusson, Markus Huber-Lang, Peter Garred, Bo Nilsson
Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels...
November 2016: Immunological Reviews
Satomi Igawa, Mari Kishibe, Masako Minami-Hori, Masaru Honma, Hisashi Tsujimura, Junko Ishikawa, Tsutomu Fujimura, Masamoto Murakami, Akemi Ishida-Yamamoto
Atopic dermatitis (AD) is a common inflammatory skin disorder. Chronic AD lesions present hyperkeratosis, indicating a disturbed desquamation process. Kallikrein-related peptidase (KLK) 7 is a serine protease involved in the proteolysis of extracellular corneodesmosome (CD) components, including desmocollin1 and corneodesmosin (Cdsn), which leads to desquamation. KLK7 is secreted by lamellar granules, and upregulated in AD lesional skin. However, despite increased KLK7 protein levels, immunostaining and electron microscopy indicated numerous CDs remaining in the uppermost layer of the stratum corneum (SC) from AD lesions...
October 18, 2016: Journal of Investigative Dermatology
Blake T Riley, Olga Ilyichova, Mauricio G S Costa, Benjamin T Porebski, Simon J de Veer, Joakim E Swedberg, Itamar Kass, Jonathan M Harris, David E Hoke, Ashley M Buckle
The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel...
October 21, 2016: Scientific Reports
M R Williams, T Nakatsuji, J A Sanford, A F Vrbanac, R L Gallo
Bacteria that reside on the skin can influence the behavior of the cutaneous immune system, but the mechanisms responsible for these effects are incompletely understood. Colonization of the skin by Staphylococcus aureus (S. aureus) is increased in atopic dermatitis (AD) and can result in increased severity of the disease. In this study we show that S. aureus stimulates human keratinocytes to increase their endogenous protease activity, including specific increases in trypsin activity. This increased protease activity coincided with increased expression of mRNA for kallikreins (KLKs), with KLK6, 13, and 14 showing the greatest induction after exposure to S...
October 17, 2016: Journal of Investigative Dermatology
Francislaine Aparecida Lívero, Jacqueline Vergutz Menetrier, Emerson Luiz Botelho Lourenço, Arquimedes Gasparotto Junior
Heart failure, hypertension, cirrhosis and nephritic syndrome are among conditions that alter volume and composition of body fluids and are modulated by diuretics. Natural products are important source of diuretics and have been considered remarkable alternative with greater effectiveness and fewer side effects. However, many of these plants used in traditional medicine must be scientifically assessed about their efficacy and toxicity. Despite the large number of published articles claiming that plants or plant-derived components may act as diuretic agents, few studies have addressed the mechanism of action of medicinal plants...
October 14, 2016: Current Pharmaceutical Design
Steven Hunt, Paul Hopkins, Nazeem Nanjee, Karen Schwander, Donald Kohan, D C Rao, Gordon Williams
OBJECTIVE: Identify the earliest hormonal, electrolyte and gene expression responses to a saline infusion before compensatory mechanisms are activated and relate these responses to delayed sodium excretion. DESIGN AND METHOD: 233 normotensive subjects with a strong positive family history of hypertension, ages 21-65, were studied on a low sodium diet before, during and after a 2-hour, 2-liter saline infusion. Plasma and urine hormones of the renin-angiotensin-aldosterone, catecholamine, uric acid, kallikrein, and cortisol pathways, microalbumin, and urine and plasma electrolytes were measured...
September 2016: Journal of Hypertension
Juan C Mayo, David Hevia, Isabel Quiros-Gonzalez, Aida Rodriguez-Garcia, Pedro Gonzalez-Menendez, Vanesa Cepas, Iván Gonzalez-Pola, Rosa M Sainz
Treatment of prostate cancer (PCa), a leading cause of cancer among males lacks successful strategies especially in advanced, hormone-refractory stages. Some clinical studies have shown an increase in neuroendocrine like cells parallel to the tumor progression but their exact role is a matter of debate. The prostate is a well-known target for melatonin, which reduces PCa cells proliferation and induces neuroendocrine differentiation. To evaluate the mechanisms underlying the indole effects on neuroendocrine differentiation and its impact on PCa progression, we used a cell culture model (LNCaP) and a murine model (TRAMP)...
October 13, 2016: Journal of Pineal Research
Zela Keuylian, Alain Hovnanian
Protease regulation plays a crucial role in skin homeostasis and inflammation as revealed by the identification of loss-of-function mutations in SPINK5 (serine protease inhibitor of Kazal type 5) in Netherton sydrome (NS). SPINK5 encodes LEKTI (lympho-epithelial Kazal type related inhibitor), a multi-domain serine protease inhibitor expressed in all stratified epithelia. Our laboratory has developed a number of murine models which have been instrumental to dissecting the pathogenesis of NS. This mini-review discusses the major findings of these models and emphasizes the role of protease regulation, especially Kallikrein related peptidases in NS...
October 6, 2016: Biological Chemistry
X S Li, X L He
Abnormal expression of the kallikrein (KLK) family of serine proteases closely correlates with onset, progression, and prognosis of endocrine gland-related malignant tumors. The aim of this study was to evaluate how downregulation of KLK12 influenced cell cycle and proliferation of the AGS gastric cancer cell line. KLK12 was detected by western blot in GES-1 normal gastric epithelial and AGS cells. AGS cells were transfected with KLK12 siRNA, a negative control siRNA, or subjected to a mock transfection, following which, we assessed mRNA and protein levels, cell proliferation, cell migration, and cell cycle progression...
August 29, 2016: Genetics and Molecular Research: GMR
Simon J de Veer, Laetitia Furio, Joakim E Swedberg, Christopher A Munro, Maria Brattsand, Judith A Clements, Alain Hovnanian, Jonathan M Harris
Proteases have pivotal roles in the skin's outermost layer, the epidermis. In the stratum corneum, serine proteases from the kallikrein-related peptidase (KLK) family have been implicated in several key homeostatic processes, including desquamation. However, the precise contribution of specific KLKs to each process remains unclear. To address this, we used a chemical biology approach and designed selective substrates and inhibitors for KLK7, the most abundant KLK protease in the stratum corneum. The resulting KLK7 inhibitor is the most potent inhibitor of this protease reported to date (Ki = 140 pM), and displays at least 1,000-fold selectivity over several proteases that are related by function (KLK5 and KLK14) or specificity (chymotrypsin)...
September 30, 2016: Journal of Investigative Dermatology
Andrew Vickers, Emily A Vertosick, Daniel D Sjoberg, Monique J Roobol, Freddie Hamdy, David Neal, Anders Bjartell, Jonas Hugosson, Jenny L Donovan, Arnauld Villers, Stephen Zappala, Hans Lilja
PURPOSE: The four-kallikrein panel, commercially available as the 4Kscore™, is a reflex test for prostate cancer early detection that has been extensively validated in multiple international cohorts. It has been suggested that use of such reflex tests be limited to those with PSA less than 10 ng/mL and negative DRE. We aimed to determine the value of the panel in men outside this "diagnostic grey zone". METHODS: We conducted an individual patient data meta-analysis using data from prior studies on the four-kallikrein panel...
September 27, 2016: Journal of Urology
Kai Cui, Yang Luan, Tao Wang, Li Zhuan, Ke Rao, Shao-Gang Wang, Zhang-Qun Ye, Ji-Hong Liu, Dao-Wen Wang
Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method...
September 27, 2016: Asian Journal of Andrology
Laura Andrade Rocha, Carlos Eli Piccinato, Mauricio Serra Ribiero, Christiane Becari, Renata Dellalibera Joviliano, Edwaldo Edner Joviliano
OBJECTIVE: The purpose of this study was to investigate the roles of the kallikrein-kinin system and matrix metalloproteinases (MMPs) in the development of arterial restenosis attributable to intimal hyperplasia in the femoropopliteal arteries. METHODS: This report describes a single-center prospective study of 27 patients with peripheral artery disease who required percutaneous transluminal angioplasty and stenting of the femoropopliteal segment using covered stent grafts...
September 22, 2016: Journal of Vascular Surgery
Steven Hunt, Paul Hopkins, Nazeem Nanjee, Karen Schwander, Donald Kohan, D C Rao, Gordon Williams
OBJECTIVE: Identify the earliest hormonal, electrolyte and gene expression responses to a saline infusion before compensatory mechanisms are activated and relate these responses to delayed sodium excretion. DESIGN AND METHOD: 233 normotensive subjects with a strong positive family history of hypertension, ages 21-65, were studied on a low sodium diet before, during and after a 2-hour, 2-liter saline infusion. Plasma and urine hormones of the renin-angiotensin-aldosterone, catecholamine, uric acid, kallikrein, and cortisol pathways, microalbumin, and urine and plasma electrolytes were measured...
September 2016: Journal of Hypertension
Saeko Kobayashi-Kinoshita, Yasuo Yamakoshi, Kazuo Onuma, Ryuji Yamamoto, Yoshinobu Asada
Transforming growth factor-β1 (TGF-β1) is present in porcine enamel extracts and is critical for proper mineralization of tooth enamel. Here, we show that the mRNA of latent TGF-β1 is expressed throughout amelogenesis. Latent TGF-β1 is activated by matrix metalloproteinase 20 (MMP20), coinciding with amelogenin processing by the same proteinase. Activated TGF-β1 binds to the major amelogenin cleavage products, particularly the neutral-soluble P103 amelogenin, to maintain its activity. The P103 amelogenin-TGF-β1 complex binds to TGFBR1 to induce TGF-β1 signalling...
2016: Scientific Reports
Dorinne Desposito, Ludovic Waeckel, Louis Potier, Christine Richer, Ronan Roussel, Nadine Bouby, Francois Alhenc-Gelas
Genetic and pharmacological studies, clinical and experimental, focused on kallikrein-K1, kinin receptors and ACE/kininase II suggest that kinin release in the settings of ischemia or diabetes reduces organ damage, especially in the heart and kidney. Kinin bioavailability may be a limiting factor for efficacy of current kinin-potentiating drugs, like ACE inhibitors. Primary activation of kinin receptors by prototypic pharmacological agonists, peptidase-resistant, selective B1 or B2, displays therapeutic efficacy in experimental cardiac and peripheral ischemic and diabetic diseases...
September 13, 2016: Biological Chemistry
Shin Iinuma, Mari Kishibe, Nao Saito, Satomi Igawa, Masaru Honma, Yoshio Bando, Shigetaka Yoshida, Akemi Ishida-Yamamoto
No abstract text is available yet for this article.
September 13, 2016: Experimental Dermatology
Mark T Bolinger, David A Antonetti
Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models...
2016: International Journal of Molecular Sciences
Yan Zhang, Liang Wang, Jin-Xin Liu, Xin-Luan Wang, Qi Shi, Yong-Jun Wang
AIMS: This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. METHODS: The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA...
November 2016: Journal of Diabetes and its Complications
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"