Review
Cell Biology
Carola E. Matus, Pamela Ehrenfeld, Carlos D. Figueroa
Summary: The human skin is a complex organ composed of the epidermis and dermis layers. The epidermis serves as a protective barrier against harmful agents, while the dermis provides support and various structures. The kallikrein family and kinins play crucial roles in maintaining skin homeostasis and regulating inflammation and cell differentiation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Medicine, General & Internal
Marcelo B. Zani, Aquiles M. Sant'Ana, Rafael C. Tognato, Jair R. Chagas, Luciano Puzer
Summary: Human tissue Kallikrein-related peptidases (hKLKs) play important roles in skin desquamation and skin diseases by cleaving corneodesmosomes and activating the PAR2 pathway. Inhibition of hKLKs shows promise as a therapeutic approach for improving the quality of life in patients with skin diseases.
FRONTIERS IN MEDICINE
(2022)
Review
Oncology
Srilakshmi Srinivasan, Thomas Kryza, Jyotsna Batra, Judith Clements
Summary: This review discusses the complex biology of kallikrein-related peptidases and their role in cancer and the tumor microenvironment. It also explores their involvement in tumor immune suppression and resistance to cancer therapy. Understanding the functions of these peptidases can provide insights into tumor development and help in developing new therapeutic strategies.
NATURE REVIEWS CANCER
(2022)
Review
Pathology
Maximilian Riedel, Holger Bronger, Viktor Magdolen, Tobias Dreyer
Summary: This review discusses the clinical relevance of KLKs in ovarian cancer and their potential as diagnostic markers. KLKs, particularly in liquid biopsies, may serve as biomarkers for early detection and prognosis assessment of ovarian cancer patients.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2021)
Article
Chemistry, Medicinal
Jordan C. LeSarge, Pierre Thibeault, Lihai Yu, Marina D. Childs, Victor M. Mirka, Qi Qi, Matthew S. Fox, Michael S. Kovacs, Rithwik Ramachandran, Leonard G. Luyt
Summary: This article reports the strategic design, synthesis, and biological evaluation of a series of novel 4-fluorobenzoylated PAR2-targeting peptides, with Isox-Cha-Chg-Ala-Arg-Dpr(4FB)NH2 being the lead candidate. This 18F-labeled tracer is the first reported PAR2 imaging agent with potential for use in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Maanvee Mirakhur, Martin Diener
Summary: Proteinases released during inflammatory or allergic responses affect gastrointestinal functions via proteinase-activated receptors. This study focuses on the effect of PAR1 and PAR2 agonists on electrogenic ion transport, tissue conductance, and muscle contractility in different segments of the gastrointestinal tract. The results suggest that the functions of PAR1 and PAR2 vary depending on the intestinal segment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Oncology
Adriana Stuardo-Parada, Rodrigo Lopez-Munoz, Franz Villarroel-Espindola, Carlos D. Figueroa, Pamela Ehrenfeld
Summary: Lung cancer is a major public health problem worldwide, and targeting surface receptors and proteases overexpressed in tumor cells, such as GPCR-family kinin receptors and KLKs, could be a promising approach for its treatment. KLK5, KLK6, KLK8, KLK11, and KLK14 have been found to play crucial roles in the progression of lung cancer. Early diagnosis, especially in high-risk populations, and modulation of kinin receptors and KLKs could have potential implications in lung cancer therapeutics.
Article
Biochemistry & Molecular Biology
Jiyoung Choi, Mi Yeon Moon, Gi Yeon Han, Moon Sik Chang, Dongki Yang, Joonseok Cha
Summary: Research shows that PM10 and PM2.5 particulate matter pose a real threat to global public health, and measuring intracellular calcium concentration in human respiratory or skin cells can reveal the impact of pollutants. Phellodendron amurense bark extract (PAE) can protect cells from air pollution damage by regulating proteinase-activated receptor-2 (PAR-2) response and expression.
Article
Cell Biology
Arundhasa Chandrabalan, Rithwik Ramachandran
Summary: Proteinase-activated receptors (PARs) in prostate cancer cells regulate tumor growth and metastasis through autocrine signaling. In this study, PAR1 and PAR2 were found to be functional in PC3 cells, while PAR4 was not expressed. The secretion of proteolytic enzymes by PC3 cells triggers cleavage of PARs, leading to autocrine signaling and the regulation of genes related to prostate cancer. PAR1 deficiency promotes cell migration and suppresses cell proliferation, while PAR2 deficiency has the opposite effects.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biology
Hyun Je Kim, Joon Ho Shim, Ji-Hye Park, Hyun Tae Shin, Jong Sup Shim, Kee-Taek Jang, Woong-Yang Park, Kyung-Hoon Lee, Eun Ji Kwon, Hyung-Suk Jang, Hanseul Yang, Jong Hee Lee, Jun-Mo Yang, Dongyoun Lee
Summary: Kim et al. utilized single-cell RNA sequencing to analyze the transcriptome profiles of human nail units, revealing distinct mesenchymal and epithelial cell populations characterized by RSPO4 and SPINK6. The study demonstrated the specific expression patterns of RSPO4 and SPINK6 in nail tissue, suggesting the potential involvement of onychofibroblasts in the pathogenesis of onychomatricoma.
COMMUNICATIONS BIOLOGY
(2021)
Article
Hematology
Magdolna Nagy, Alejandro Pallares Robles, Mayken Visser, Thomas Koeck, Vincent ten Cate, Arina J. ten Cate-Hoek, Stephan Schwers, Stefan Heitmeier, Hugo ten Cate, Philipp S. Wild, Henri M. H. Spronk
Summary: This study found that FXIa levels were elevated in patients with acute VTE and were associated with recurrent VTE, suggesting a significant risk contribution of FXI activation to VTE. The findings support the use of FXIa inhibition in the setting of acute VTE.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Somayeh Shatizadeh Malekshahi, Jila Yavarian, Nazanin-Zahra Shafiei-Jandaghi
Summary: Coronaviruses, including SARS-CoV-2, use various host receptors for cell entry. The choice of peptidases as receptors by some HCoVs may be related to their widespread presence on target cells and the viruses' preference for molecules with relatively low affinity as well as evolutionary conservation of these receptors allowing the viruses to switch between host species. Additionally, this selection process may reflect the trial and error nature of evolution.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Ying Xie, Lindsey Fontenot, Andrea Chupina Estrada, Becca Nelson, Jiani Wang, David Q. Shih, Wendy Ho, S. Anjani Mattai, Florian Rieder, Dane D. Jensen, Nigel W. Bunnett, Hon Wai Koon
Summary: The study demonstrates that Elafin can suppress collagen synthesis in intestinal fibroblasts by inhibiting protease-activated receptor 2, which is dependent on cathelin S, leading to a reduction in intestinal fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
M. Rodriguez-Rios, G. Rinaldi, A. Megia-Fernandez, A. Lilienkampf, C. T. Robb, A. G. Rossi, M. Bradley
Summary: We describe a FRET-based, tri-branched near infrared probe for specific detection of human neutrophil elastase. The probe enables selective detection of activated neutrophils and labeling of neutrophil extracellular traps. It emits in the NIR region with minimal interference from endogenous biomolecules and autofluorescence.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
M. Rodriguez-Rios, G. Rinaldi, A. Megia-Fernandez, A. Lilienkampf, C. T. Robb, A. G. Rossi, M. Bradley
Summary: In this study, a near infrared probe based on FRET technology was developed for specific detection of human neutrophil elastase. The probe selectively detects activated neutrophils and can label neutrophil extracellular traps.
CHEMICAL COMMUNICATIONS
(2023)
Article
Oncology
Kristina Stefansson, Husam Oda, Charlotte Ofverman, Eva Lundin, Hakan Hedman, David Lindquist
Meeting Abstract
Dermatology
A. S. Oak, T. Kim, G. Bocheva, M. Elsayed, A. A. Brozyna, Z. Janjetovic, M. Athar, A. T. Slominski
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2019)
Article
Endocrinology & Metabolism
Erik Bovinder Ylitalo, Elin Thysell, Camilla Thellenberg-Karlsson, Marie Lundholm, Anders Widmark, Anders Bergh, Andreas Josefsson, Maria Brattsand, Pernilla Wikstrom
Article
Oncology
Allen S. W. Oak, Georgeta Bocheva, Tae-Kang Kim, Anna A. Brozyna, Zorica Janjetovic, Mohammad Athar, Robert C. Tuckey, Andrzej T. Slominski
ANTICANCER RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Desislav Tomov, Georgeta Bocheva, Vidka Divarova, Lilia Kasabova, Dobrin Svinarov
Summary: This study developed and validated an LC-MS/MS method for determining 8-iso-Prostaglandin F2 alpha in human plasma using a modified liquid-liquid extraction procedure with phase separation. The modified sample preparation procedure resulted in higher extraction yield, clear separation of organic layer, and better-purified product for instrumental analysis. The method met industrial validation criteria and allowed accurate determination of 8-iso-PGF(2 alpha) in human plasma at a diagnostically significant concentration range.
JOURNAL OF MEDICAL BIOCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Georgeta St Bocheva, Radomir M. Slominski, Andrzej T. Slominski
Summary: The aging skin undergoes immunosenescence and immunological alterations, which together with environmental stressors and genetic factors can lead to immune dysregulation and epidermal barrier abnormalities, facilitating the late onset of atopic dermatitis (AD) in the elderly. While healthy aged skin shows overproduction of cytokines, older AD patients have decreased levels of Th2/Th22 related cytokines and increased expression of terminal differentiation markers, reflecting the persistence of AD in an aged skin environment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Georgeta Bocheva, Radomir M. Slominski, Andrzej T. Slominski
Summary: The active metabolites of vitamin D-3 and lumisterol have antiaging and photoprotective effects on the skin through immunomodulation, antioxidative responses, and DNA repair mechanisms. They interact with multiple nuclear receptors and have potential for preventing, attenuating, or treating premature skin aging. Further clinical evaluation of topically applied derivatives is needed for future trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Erik Bovinder Ylitalo, Elin Thysell, Mattias Landfors, Maria Brattsand, Emma Jernberg, Sead Crnalic, Anders Widmark, Magnus Hultdin, Anders Bergh, Sofie Degerman, Pernilla Wikstrom
Summary: Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis.
CLINICAL EPIGENETICS
(2021)
Review
Dermatology
Miroslava Kadurina, Jana Kazandjieva, Georgeta Bocheva
Summary: PLE is an immunologically mediated photodermatosis, associated with immune disturbances. Preventive treatment includes the use of sunscreens and photohardening. Treatment options include phototherapy, glucocorticoids, among others.
DERMATOLOGIC THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Georgeta Bocheva, Radomir M. Slominski, Zorica Janjetovic, Tae-Kang Kim, Markus Boehm, Kerstin Steinbrink, Russel J. Reiter, Konrad Kleszczynski, Andrzej T. Slominski
Summary: The skin, as the largest organ in the human body, is prone to aging due to both internal and external factors. Aging is characterized by clinical features and changes in cellular and extracellular components. Melatonin and its metabolites have the potential to counteract skin aging by regulating molecular mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ake Lundwall, Erik Bovinder Ylitalo, Pernilla Wikstroem, Maria Brattsand
Summary: KLK4 and its splice variant KLK4T2, as well as the pseudogene KLKP1, show differential expression patterns in prostate tissue, with potential implications for prostate cancer and benign prostatic hyperplasia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Malin Mickelsson, Elisabet Soderstrom, Kristina Stefansson, Jonas Andersson, Stefan Soderberg, Johan Hultdin
Summary: The study reveals that smoking is associated with a higher eGFR, with gender differences in the effect, while snus does not have an impact on eGFR.
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
(2021)
Article
Biotechnology & Applied Microbiology
Georgeta Bocheva, Lina Malinova, Dimitar Bakalov, Georgi Bogdanov, Julieta Hristova, Dobrin Svinarov
Summary: Skin manifestations in hypothyroidism are common but treatment options are limited. Pentoxifylline (PTX) has shown potential in inhibiting fibroblast activation and glycosaminoglycans synthesis, suggesting it could be a new therapeutic agent for thyroid-associated dermatopathy (TAD).
BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT
(2022)
Article
Oncology
Helena Jaeremo, Julius Semenas, Sofia Halin Bergstroem, Marie Lundholm, Elin Thysell, Anders Widmark, Sead Crnalic, Erik Bovinder Ylitalo, Anders Bergh, Maria Brattsand, Pernilla Wikstroem
Summary: In prostate cancer progression to bone metastasis, certain miRNAs, including miRNA-23c and -4328, are downregulated and these changes impact the growth of prostate cancer. The downregulation of these miRNAs may result in a loss of tumor suppressive effects, providing potential biomarkers and treatment possibilities for further exploration.
Article
Veterinary Sciences
Dimitar Bakalov, Petar Iliev, Zafer Sabit, Radka Tafradjiiska-Hadjiolova, Georgeta Bocheva
Summary: This study aimed to examine the changes in behavior, cognition, and memory in rats with PTU-induced overt hypothyroidism and the effects of tryptophan treatment on this state. The results showed significant differences in the behavioral patterns of the hypothyroid rats, including reduced locomotor activity, rearing, and memory function, which were alleviated by treatment with 5-OH-TRP. These findings have important implications for further investigation of functional and structural changes in the hippocampus during a hypothyroid state and the effects of serotonin mediation on hypothyroid-associated depressive behavior.
VETERINARY SCIENCES
(2023)