Inflammation, an innate immune response mediated by macrophages, forms the first line of defence to protect our body from the invasion of various pathogens. Although inflammation is a defensive response, chronic inflammation has been regarded as the major cause of many types of human diseases such as inflammatory/autoimmune diseases, cancers, neurological diseases, and cardiovascular diseases. Folate receptor (FR) is a cell surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein, and its three isoforms, FR-α, FR-β, and FR-γ, are found in humans. Interestingly, FRs are highly expressed on a variety of cells, including cancer cells and activated macrophages, whereas their expression on normal cells is undetectable, indicating that FR-targeting could be a good selective strategy for the diagnosis and therapeutic treatment of cancers and activated macrophage-mediated inflammatory diseases. Previous studies successfully showed FR-targeted imaging of many types of cancers in animal models as well as human patients. Recently, a number of emerging studies have found that activated macrophages, which are critical players for a variety of inflammatory diseases, highly express FRs, and selective targeting of these FR-positive activated macrophages is a good approach to diagnose and treat inflammatory diseases. In this review, we describe the characteristics and structure of FRs, and further discuss FR-targeted diagnostics and therapeutics of human diseases, in particular, activated macrophage-mediated inflammatory diseases.
Cardiovascular Diseases ; Diagnosis ; Folic Acid* ; Glycoproteins ; Glycosylphosphatidylinositols ; Humans ; Immunity, Innate ; Inflammation ; Macrophages ; Models, Animal ; Protein Isoforms

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.
Arthritis, Rheumatoid ; Autoimmunity ; Cytokines ; Inflammasomes* ; Inflammation ; Interleukin-18 ; Interleukins ; Lupus Erythematosus, Systemic ; Macrophages ; Multiprotein Complexes ; Myeloid Cells ; Pyroptosis ; Rheumatic Diseases* ; Spondylitis, Ankylosing

Inflammation is an immune response mediated by innate immune cells of tissues, against invading microbes and cellular stress. The hallmark of inflammatory responses is the activation of inflammasomes — multiprotein oligomers comprising intracellular pattern recognition receptors and inflammatory effectors — such as ASC and pro-cysteine-aspartic protease (pro-caspase)-1. Inflammasomes can be classified as canonical or non-canonical, and their activation in response to various ligands commonly induces caspase-1 activation and gasdermin D (GSDMD) processing, leading to caspase-1-mediated maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18, and GSDMD-mediated pyroptosis through pore generation in cell membranes. Although inflammation protects the host from harmful stimuli, chronic inflammation is a critical risk factor for inflammatory diseases, and several studies have investigated the role of canonical inflammasomes in inflammatory responses and diseases, with emerging studies focusing on the role of non-canonical inflammasomes. This review discusses recent studies on the regulatory roles of the caspase-11 non-canonical inflammasome in the pathogenesis of inflammatory diseases. Additionally, it provides an insight into the development of novel therapeutics based on targeting caspase-11 non-canonical inflammasome and its downstream effectors to prevent and treat human inflammatory conditions.
Cell Membrane ; Cytokines ; Humans ; Inflammasomes* ; Inflammation ; Interleukin-18 ; Ligands ; Pyroptosis ; Receptors, Pattern Recognition ; Risk Factors

The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases.Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.

The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases.Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.

The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases.Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.

The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases.Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.

The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases.Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.

In order to find out the distribution of fibronectin and fibrinogen in placenta among pregnancy induced hypertensive (PIH) patients, 6 normotensive pregnancies and 17 PIH patients were chosen. The placentas were obtained right after delivery and soaked in the 10% formalin solution. The score was measured in terms of the positiveness of the stain in immunohistochemical stain by using I antibody with the rabbit antihuman fibronectin and the rabbit anti-human fibrinogen. Comparison between two groups are as following: 1.The placenta of PIH patients showed significantly reduced positiveness of fibronectin in their fetal villous vessels and villous stroma. 2. In the PIH patients, the positiveness was reduced in the group giving the birth to intrauterine fetal growth retardation compared to giving birth to normal baby. 3. In both normotensive and PIH patients, the villous basement membrane did not show the staining response to fibronectin, while showing heavy staining response to fibrinogen. 4. The positiveness of fibrinogen in fetal vessels, villous basement membrane, intervillous space and stroma were almost same in both normotensive and PIH patients. From above results, we can conclude that there is abnormality in the distribution of fibronectin especially in the fetal vessels and the villous stroma of placenta among PIH patients. The cause of this result needs further study.
Basement Membrane ; Fetal Growth Retardation ; Fibrinogen* ; Fibronectins* ; Formaldehyde ; Humans ; Parturition ; Placenta* ; Pre-Eclampsia ; Pregnancy*

The incidence of ectpic pregnancy has increased rapidly over the past decade. Currently, the complications of this disorder make it one of the leading causes of maternal mortality and morbidity. In the late 1980s, reports of successful use of methotrexate (MTX) as a non surgical treatment for ectopic pregnancy (EP) also began to appear in the literature. With MTX emerging as a possible alternative management of selected women with an EP, an analysis of its comparative costs is now needed. We examined retrospectively the costs associated with management of EP in our hospital. We selected 30 women with EPand divided them into two groups of MTX treated group (n= l0) and surgically treated group (n=20). There were no statistically significant differences in the doctors fee, room, charge and cost of laboratory and radiologic examination between two groups. But We found significant reduction in cost with regard to pharmacy, injection, procedure and operation of MTX treated group compared to surgically treated group (p<0.05). Consequently the use of MTX for EP should still be considered investigational; we recognize and agree that the evolution of this remedial option should be based primarily on its ability to decrease morbidity and mortality rather than on its ability to reduce costs. If medical treatment proves to be effective, the potential cost savings demonstrated in this report will become an important influential factor on selecting alternative remedy.
Cost Savings ; Fees and Charges ; Female ; Humans ; Incidence ; Maternal Mortality ; Methotrexate ; Mortality ; Pharmacy ; Pregnancy ; Pregnancy, Ectopic* ; Retrospective Studies