ABSTRACT
Interleukin receptor-associated kinase (IRAK) proteins are pivotal in interleukin-1 and Toll-like receptor-mediated signaling pathways. They play essential roles in innate immunity and inflammation. This review analyzes and discusses the physiological functions of IRAK1 and its associated diseases. IRAK1 is involved in a wide range of diseases such as dry eye, which highlights its potential as a therapeutic target under various conditions. Various IRAK1 inhibitors, including Pacritinib and Rosoxacin, show therapeutic potential against malignancies and inflammatory diseases. The covalent IRAK1 inhibitor JH-X-119-01 shows promise in B-cell lymphomas, emphasizing the significance of covalent bonds in its activity. Additionally, the emergence of selective IRAK1 degraders, such as JNJ-101, provides a novel strategy by targeting the scaffolding function of IRAK1. Thus, the evolving landscape of IRAK1-targeted approaches provides promising avenues for increasingly safe and effective therapeutic interventions for various diseases.
Subject(s)
Interleukin-1 Receptor-Associated Kinases , Interleukin-1 Receptor-Associated Kinases/metabolism , Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors , Humans , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Animals , Inflammation/drug therapy , Inflammation/metabolism , Signal Transduction/drug effects , Neoplasms/drug therapy , Neoplasms/metabolismABSTRACT
Targeted protein degradation (TPD) is a promising therapeutic modality that has garnered attention in academic, industrial, and pharmaceutical research for treating diseases such as cancer, neurodegenerative disorders, inflammation, and viral infections. In this context, proteolysis-targeting chimeras (PROTACs) present a reliable technology for degrading disease-causing proteins. PROTACs complement small-molecule inhibitors, which primarily rely on direct protein regulation. From concept-to-clinic, PROTACs have evolved from cell impermeable peptide molecules to orally bioavailable drugs. Despite their potential in medicinal chemistry, certain aspects regarding PROTACs remain unclear. The clinical significance of PROTACs is primarily limited owing to their lack of selectivity and drug-like properties. This review focused on recently reported PROTAC strategies, particularly in 2022. It aimed to address and overcome the challenges posed by classical PROTACs by correlating them with emerging approaches with improved selectivity and controllability, cell permeability, linker flexibility, druggability, and PROTAC-based approaches, developed in 2022. Furthermore, recently reported PROTAC-based approaches are discussed, highlighting each of their advantages and limitations. We predict that several improved PROTAC molecules will be accessible for treating patients exhibiting various conditions, including cancer, neurodegenerative disorders, inflammation, and viral infections.
Subject(s)
Neoplasms , Proteins , Humans , Proteolysis , Proteins/chemistry , Ubiquitin-Protein Ligases/metabolismABSTRACT
Melanocortins play crucial roles in regulating the stress response, inflammation, and skin pigmentation. In this review, we focus on the melanocortin 1 receptor (MC1R), a G protein-coupled receptor primarily known for regulating skin pigmentation and exhibiting anti-inflammatory effects. First, we provide an overview of the structure, signaling pathways, and related diseases of MC1R. Next, we discuss the potential therapeutic use of synthetic peptides and small molecule modulators of MC1R, highlighting the development of various drugs that enhance stability through amino acid sequence modifications and small molecule drugs to overcome limitations associated with peptide characteristics. Notably, MC1R-targeted drugs have applications beyond skin pigmentation-related diseases, which predominantly affect MC1R in melanocytes. These drugs can also be useful in treating inflammatory diseases with MC1R expression present in various cells. Our review underscores the potential of MC1R-targeted drugs to treat a wide range of diseases and encourages further research in this area.
Subject(s)
Melanocytes , Receptor, Melanocortin, Type 1 , Melanocytes/metabolism , Peptides/pharmacology , Receptor, Melanocortin, Type 1/genetics , Receptor, Melanocortin, Type 1/metabolism , Signal Transduction , Skin Pigmentation , HumansABSTRACT
Quinazolines are a privileged class of nitrogen-containing heterocycles, widely present in a variety of natural products and synthetic chemicals with a broad spectrum of biological and medicinal activities. Owing to their pharmaceutical applications and promising biological value, a variety of synthetic methodologies have been reported for these scaffolds. From the perspective of green and sustainable chemistry, transition-metal-free synthesis provides an alternative method for accessing several biologically active heterocycles. In this review, we summarize the recent progress achieved in the transition-metal-free synthesis of quinazolines and we cover the literature from 2015 to 2022. This aspect is present alongside the advantages, limitations, mechanistic rationalization, and future perspectives associated with the synthetic methodologies.
ABSTRACT
The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1ß and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Lactones/pharmacology , Macrolides/pharmacology , NF-kappa B/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cell Line , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Lactones/chemical synthesis , Macrolides/chemical synthesis , Molecular Structure , NF-kappa B/metabolism , Rats , Structure-Activity RelationshipABSTRACT
Drug resistance continues to be a major problem associated with cancer treatment. One of the primary causes of anticancer drug resistance is the frequently mutated RAS gene. In particular, considerable efforts have been made to treat KRAS-induced cancers by directly and indirectly controlling the activity of KRAS. However, the RAS protein is still one of the most prominent targets for drugs in cancer treatment. Recently, novel targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras, have been developed to render "undruggable" targets druggable and overcome drug resistance and mutation problems. In this study, we discuss small-molecule inhibitors, TPD-based small-molecule chemicals for targeting RAS pathway proteins, and their potential applications for treating KRAS-mutant cancers. Novel TPD strategies are expected to serve as promising therapeutic methods for treating tumor patients with KRAS mutations.
Subject(s)
Neoplasms/drug therapy , Proteolysis/drug effects , Proto-Oncogene Proteins p21(ras)/genetics , Small Molecule Libraries/therapeutic use , Drug Resistance, Neoplasm/genetics , Humans , Mutation/drug effects , Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Signal Transduction/drug effectsABSTRACT
Imperata cylindrica is a medicinal plant native to southwestern Asia and the tropical and subtropical zones. To date, 72 chemical constituents have been isolated and identified from I. cylindrica Among these compounds, saponins, flavonoids, phenols, and glycosides are the major constituents. Investigations of pharmacological activities of I. cylindrica revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including immunomodulatory, antibacterial, antitumor, anti-inflammatory, and liver protection activities both in vivo and in vitro. The purpose of this review is to provide an overview of I. cylindrica studies until 2019. This article also intends to review advances in the botanical, phytochemical, and pharmacological studies and industrial applications of I. cylindrica, which will provide a useful bibliography for further investigations and applications of I. cylindrica in medicines and foods.
Subject(s)
Plant Extracts/pharmacology , Poaceae/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Diuretics/chemistry , Diuretics/pharmacology , Humans , Patents as Topic , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Poaceae/physiologyABSTRACT
Despite numerous reports on the beneficial effects of catechin or epicatechin contained in tea and cacao extract on human health, a conclusive and precise molecular mechanism has not been elucidated. Metabolism of chemical compounds in gut microbiota recently gained significant attention, and extensive studies have been devoted in this field. In conjunction with these results, our group focused on the anti-inflammatory effects of both enantiomers of DHPV (5-(3',4'-dihydroxyphenyl)-γ-valerolactone), produced in the intestine by microbiota metabolism, on IEC-6 cells. Divergent and efficient enantioselective synthesis of (S)- and (R)-DHPV was efficiently achieved by cross-metathesis and Sharpless asymmetric dihydroxylation as a key reaction for four steps in 16% and 14% overall yields, respectively. The anti-inflammatory effects of two enantiomers were tested on IEC-6 cells, and we found that (S)-DHPV was more active than (R)-DHPV. This result implicates that the metabolite produced in the gut has beneficial effects on IEC-6 cells of rat intestines, and the chirality of the metabolite is important for its anti-inflammatory activity. This also provided information for the future discovery of novel small molecular therapeutics for the treatment of inflammatory bowel disease.
Subject(s)
Anti-Inflammatory Agents , Inflammatory Bowel Diseases/drug therapy , Intestinal Mucosa/metabolism , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Line , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/pathology , Lactones/chemical synthesis , Lactones/chemistry , Lactones/pharmacology , RatsABSTRACT
Liver fibrosis is characterized by formation of scar tissue in the liver. The role of STAT3 signaling has been implicated on activating hepatic stellate cells (HSC) to myofibroblast-like cells in liver fibrosis. Major factors that activate STAT3 signaling are TGF-ß1 and IL-6, which are upregulated in the liver in patients afflicted with liver fibrosis. Recent reports indicate that not only IL-6, but also the non-canonical signaling pathway of TGF-ß1 is associated with STAT3 signaling. In this study, we demonstrate a new function of the STAT3 inhibitor, STX-0119, in liver fibrosis. STX-0119 is an inhibitor of STAT3 dimerization, which is required for nuclear localization of STAT3. We first investigated the anti-fibrotic effect of STX-0119 in in vitro experiments. Exposure to STX-0119 inhibited the nuclear localization of STAT3 in HSCs, resulting in decreased expression of its target genes, such as col1a1 and αSMA. In addition, STX-0119 also inhibited the TGF-ß1/IL-6-induced activation of HSCs. Next, we examined the in vivo effect of STX-0119 in the liver fibrosis mouse model using thioacetamide (TAA) and carbon tetrachloride (CCl4). STX-0119 attenuated the TAA-induced liver fibrosis by inhibiting activation of HSCs to myofibroblast-like cells. Consistent with the in vivo results using TAA-induced liver fibrosis model, treatment of STX-0119 similarly attenuated CCl4-induced liver fibrosis. In conclusion, we believe that STX-0119 inhibits the development of liver fibrosis by blocking the activation of hepatic stellate cells. These results indicate that STX-0119 is a potential new therapeutic strategy to prevent disease progression to cirrhosis.
Subject(s)
Hepatic Stellate Cells/drug effects , Liver Cirrhosis/drug therapy , Oxadiazoles/therapeutic use , Quinolines/therapeutic use , STAT3 Transcription Factor/antagonists & inhibitors , Animals , Cell Proliferation/drug effects , Collagen/analysis , Hepatic Stellate Cells/pathology , Liver Cirrhosis/pathology , Male , Mice , Mice, Inbred C57BLABSTRACT
Photodynamic therapy is a clinically approved treatment approach for cancer. However, it has limited applications owing to poor water solubility and the short wavelength absorption of the photosensitizer (PS). We selected a near-infrared photosensitizer, SiNC, and encapsulated into a gold nanocage (AuNC) in the presence of phase-changing material. Then, the PS-encapsulated nanocage was coated with glycol chitosan (GC) with a cleavable peptide linkage or stable cysteine linkage to protect the PS from premature release and to improve the biocompatibility of the nanocage. We obtained particles of GC-coated SiNC-encapsulated AuNC with a neutral surface charge and approximately 160â¯nm in size. The enzyme-cleavable peptide-linked GC formulation (GC-pep@SiNC-AuNC) showed stronger phototoxicity and tumor suppression efficacy in a glioblastoma model compared with free NIR-PS and stable cysteine-linked GC-AuNC (GC-cys@SiNC-AuNC). This polymer-coated SiNC-AuNC may be a promising agent for brain cancer phototherapy.
Subject(s)
Chitosan/chemistry , Glioblastoma/therapy , Gold/chemistry , Infrared Rays , Metal Nanoparticles/chemistry , Photosensitizing Agents/therapeutic use , Phototherapy , Animals , Cell Line, Tumor , Chitosan/chemical synthesis , Endocytosis , Humans , Metal Nanoparticles/ultrastructure , Mice, Inbred BALB C , Mice, Nude , Peptides/chemical synthesis , Peptides/chemistry , Proton Magnetic Resonance Spectroscopy , Tissue DistributionABSTRACT
Parasitic diseases have serious health, social, and economic impacts, especially in the tropical regions of the world. Diseases caused by protozoan parasites are responsible for considerable mortality and morbidity, affecting more than 500 million people worldwide. Globally, the burden of protozoan diseases is increasing and is been exacerbated because of a lack of effective medication due to the drug resistance and toxicity of current antiprotozoal agents. These limitations have prompted many researchers to search for new drugs against protozoan parasites. In this review, we have compiled the latest information (2012-2017) on the structures and pharmacological activities of newly developed organic compounds against five major protozoan diseases, giardiasis, leishmaniasis, malaria, trichomoniasis, and trypanosomiasis, with the aim of showing recent advances in the discovery of new antiprotozoal drugs.
Subject(s)
Antiprotozoal Agents/therapeutic use , Parasites/drug effects , Parasitic Diseases/drug therapy , Animals , Drug Resistance/drug effects , Parasites/pathogenicity , Parasitic Diseases/classification , Parasitic Diseases/epidemiology , Parasitic Diseases/parasitologyABSTRACT
The hormone glucagon increases blood glucose levels through increasing hepatic glucose output. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, the inhibition of glucagon receptor is one target for the treatment of hyperglycemia in type 2 diabetes. Here we designed and synthesized a series of small molecules based on phenylpyrimidine. Of these, the compound (R)-7a most significantly decreased the glucagon-induced cAMP production and glucagon-induced glucose production during in vitro and in vivo assays. In addition, (R)-7a showed good efficacy in glucagon challenge tests and lowered blood glucose levels in diabetic db/db mice. Our results suggest that the compound (R)-7a could be a potential glucose-lowering agent for treating type 2 diabetes.
Subject(s)
Hypoglycemic Agents/therapeutic use , Pyrimidines/therapeutic use , Receptors, Glucagon/antagonists & inhibitors , Animals , Blood Glucose/analysis , Blood Glucose/metabolism , CHO Cells , Cricetulus , Cyclic AMP/metabolism , Diabetes Mellitus, Experimental/drug therapy , Hepatocytes/drug effects , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/toxicity , Male , Mice, Inbred C57BL , Pyrimidines/chemical synthesis , Pyrimidines/pharmacokinetics , Pyrimidines/toxicity , StereoisomerismABSTRACT
In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5-14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC50 values (0.14-1.26µM) lower than the standard drug metronidazole (IC50 1.80µM). All nine compounds exhibited antimalarial activity (IC50 range: 1.42-19.62µM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC50 range: 14.67-81.24µM) than quinine (IC50: 275.6±16.46µM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Chloroquine/chemistry , Piperazines/chemistry , Antimalarials/chemistry , Antimalarials/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Binding Sites , Cell Line , Cell Survival/drug effects , Entamoeba histolytica/drug effects , Erythrocytes/drug effects , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Piperazine , Plasmodium falciparum/drug effects , Protein Structure, Tertiary , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Structure-Activity Relationship , Thioredoxin-Disulfide Reductase/chemistry , Thioredoxin-Disulfide Reductase/metabolismABSTRACT
A large number of protozoans infect humans but Entamoeba histolytica is the only organism responsible for causing amoebiasis, a deadly disease after malaria. Numerous heterocycle-based antiamoebic agents have been previously synthesized as E. histolytica inhibitors and while some of these agents have shown moderate activity, the search for a novel and ideal antiamoebic compound is still ongoing. In this digest Letter, we present the latest data on antiamoebic agents from 2011 to 2016 based on the different classes of heterocyclic agents.
Subject(s)
Antiprotozoal Agents/pharmacology , Entamoeba histolytica/drug effects , Animals , Cell Line , Drug Discovery , Heterocyclic Compounds/pharmacology , Humans , Inhibitory Concentration 50ABSTRACT
The present study reports the cancer chemopreventive activities of phenyl polyyne diols derived from polyacetylene triol. Thirty-seven analogues based on a 1-phenylhexa-2,4-diyne-1,6-diol scaffold were prepared and their effects on QR activity were elucidated, as well as their cytotoxicities. We found that most of the derivatives based on phenylhexa-2,4-diyne-1,6-diol exhibited good QR induction activity and relatively low cytotoxicity and systemic structure-activity relationship was revealed. In particular, 4-fluorophenyl, 3-chlorophenyl, and 3,4-dioxolophenyl derivatives showed the best profiles in terms of QR induction, cytotoxicity, and CI.
Subject(s)
Anticarcinogenic Agents/chemistry , Anticarcinogenic Agents/pharmacology , Polyynes/chemistry , Polyynes/pharmacology , Structure-Activity RelationshipABSTRACT
The prevalence and clinical features of psoriatic arthritis (PsA) in psoriasis patients vary widely in different countries, and studies on Korean population are rarely reported. The aim of this study was to investigate the clinical features of PsA in a Korean population of patients with psoriasis by using psoriatic arthritis screening questionnaires. A cross-sectional observational study was conducted, and consecutive psoriatic patients were evaluated for PsA by using two kinds of psoriatic arthritis screening questionnaires: Psoriatic Arthritis Screening and Evaluation tool (PASE) and Psoriasis Epidemiology Screening Tool (PEST). Psoriatic patients with higher score in screening questionnaires were referred to rheumatologist for confirmative diagnosis of PsA. Among 196 psoriasis patients screened by PASE and PEST, total prevalence of PsA was 11.2 % (n = 22/196) with 59.1 % of the cases being newly diagnosed. Compared with patients without PsA, patients with PsA had more extensive psoriasis, higher frequency of pustular and inverse type of psoriasis, and lower frequency of plaque type of psoriasis. Spondylitis was the most common manifestation pattern, followed by polyarthritis, oligoarthritis, predominant distal interphalangeal arthritis, and arthritis mutilans. Our findings are consistent with a low prevalence of PsA among patients with psoriasis in Asia. We also confirm a spondylitis as the most common pattern of PsA in Korea. PsA screening questionnaires can be a simple and useful tool to screen PsA in patients with psoriasis.
Subject(s)
Arthritis, Psoriatic/diagnosis , Psoriasis/diagnosis , Spondylitis/diagnosis , Surveys and Questionnaires , Adult , Arthritis, Psoriatic/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Psoriasis/epidemiology , Republic of Korea/epidemiology , Spondylitis/epidemiologyABSTRACT
In the present study, the fractionation scheme for cysteinyl peptide enrichment (CPE) was combined with the mass differential tags for relative and absolute quantification (mTRAQ) method to reduce sample complexity and increase proteome coverage. Cysteine residues of the proteins were first alkylated using iodoacetyl PEG2-biotin instead of other conventional alkylating agents such as iodoacetamide. After trypsin digestion, amine groups were labeled with mTRAQ, and these labeled peptides were fractionated according to the presence or absence of cysteine residues using avidin-biotin affinity chromatography. With these approaches, we were able to divide the peptides into the two fractions with more than 90% fractionation efficiency for standard protein and MCF7 cell lysate. When the fractionation strategy was applied to colorectal cancer tissue samples, we were able to obtain quantitative information that was consistent with the previous study based on mTRAQ quantification, implying that the cysteine-based fractionation method does not affect mTRAQ quantification. We expect that the mTRAQ-based quantitative analysis combined with peptide fractionation through the CPE strategy would allow for deep-down analysis of proteome samples and ultimately for increasing proteome coverage with simultaneous quantification for biomarker discovery.
Subject(s)
Cysteine , Isotope Labeling/methods , Mass Spectrometry/methods , Peptides/chemistry , Proteomics/methods , Humans , MCF-7 Cells , Peptides/metabolism , Proteolysis , Trypsin/metabolismABSTRACT
An increasing importance of chemoprevention for controlling cancer risks prompted the discovery of new active cancer chemopreventive agents. In this study, we designed and synthesized substituted hexa-2,4-diyne-1,6-diols, more structurally simplified, tunable, and easily preparable than natural gymnasterkoreaynes, and evaluated their cancer chemopreventive activities by measuring concentration of doubling quinone reductase activity (CD), cell viability, and chemopreventive index (CI). Most of the diols exhibited good CD activity and low cytotoxicity. In particular, tetradeca-5,7-diyne-4,9-diol and 2-methyltetradeca-5,7-diyne-4,9-diol showed the best cancer chemopreventive activity, approximately equipotent to that of sulforaphane. And, by synthesizing optically active stereoisomers of selected active compounds, the effect of stereochemistry was also studied. Eventually, we produced a chemopreventive compound for in vivo study.
Subject(s)
Acetylene/pharmacology , Anticarcinogenic Agents/pharmacology , Neoplasms/prevention & control , Acetylene/chemical synthesis , Acetylene/chemistry , Anticarcinogenic Agents/chemical synthesis , Anticarcinogenic Agents/chemistry , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Design , Hep G2 Cells , Humans , Molecular Structure , NAD(P)H Dehydrogenase (Quinone)/metabolism , Structure-Activity RelationshipABSTRACT
Cutaneous vasculitis can be limited to skin or a manifestation of primary systemic vasculitis. However, there are no definite markers to predict systemic involvements. Recent studies have shown that a higher red blood cell distribution width (RDW) is associated with disease activity in various disorders. We evaluated whether RDW can be used as an indicator for predicting systemic disease in patients with initial cutaneous involvements. We reviewed clinical and laboratory information of 143 patients with cutaneous vasculitis and 15 pigmented purpuric dermatosis patients seen at single academic hospital in Korea. Various parameters, including RDW, were evaluated in patients with primary cutaneous vasculitis and primary systemic vasculitis with initial cutaneous manifestations. The RDW value between cutaneous and systemic vasculitis patients was compared and RDW level was also investigated whether it can indicate systemic vasculitis in patients with cutaneous involvements. The mean age was 32.0 years, and 102 (64.6 %) patients were female. A total of 132 patients were patients with primary cutaneous vasculitis, and 11 were primary systemic vasculitis. Higher ratio of patients with high RDW was detected in systemic vasculitis group compared with cutaneous vasculitis group (36.4 vs. 7.6 %, P < 0.05). The mean RDW was significantly higher in systemic vasculitis patients (P < 0.05). RDW had the strongest association with systemic vasculitis (P < 0.05, OR 1.834). In conclusion, elevated level of RDW was significantly associated with systemic vasculitis. RDW can be used as one of the marker to predict systemic disease in patients with cutaneous vasculitis.
Subject(s)
Erythrocytes , Systemic Vasculitis/diagnosis , Vasculitis, Leukocytoclastic, Cutaneous/complications , Adolescent , Adult , Biomarkers/blood , Erythrocyte Indices , Female , Humans , Male , Middle Aged , Prognosis , Systemic Vasculitis/blood , Systemic Vasculitis/complications , Vasculitis, Leukocytoclastic, Cutaneous/blood , Young AdultABSTRACT
Next-generation sequencing (NGS) technologies recently developed are now used for study of genomes from various organisms. Sequencing-by-synthesis (SBS) is a key strategy in the NGS. The SBS uses nucleotides so-called dual-modified reversible terminators (DRTs) in which bases are labeled with fluorophores and 3'-OH is protected with a reversibly cleavable chemical group, respectively. In this study, we examined the possibility of performing SBS with mono-modified reversible terminators (MRTs), in which the reversible blocking group on the 3'-OH plays a dual role as a fluorescent signal report as well as a chemical protection. We studied cyclic reversible termination by using two MRTs (dA and dT), wherein the modifications were two different fluorophores and cleavable to regenerate a free 3'-OH. We here demonstrated that SBS could be achieved with incorporation of MRTs by a DNA polymerase and correct base-calls based on the two different colors from the fluorophores.