scholarly journals Role of Human Galectins in Inflammation and Cancers Associated with Endometriosis

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 230 ◽  
Author(s):  
Brooke V. Hisrich ◽  
R. Brant Young ◽  
Alison M. Sansone ◽  
Zachary Bowens ◽  
Lisa J. Green ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Immune Surveillance ◽  
Chronic Inflammatory Disease ◽  
Cellular Growth ◽  
Unknown Etiology ◽  
Cancer Therapies ◽  
Cellular Functions ◽  
Inflammatory Conditions ◽  
Galectin 3 ◽  
Kras Protein

Galectins are a family of β-galactoside-binding proteins that contribute to multiple cellular functions, including immune surveillance and apoptosis. Human galectins are also important regulators of inflammation, making them a research target for various inflammatory diseases and tumorigenesis associated with pro-inflammatory conditions. This review focuses on the involvement of human galectins in modulation of inflammation and in the pathophysiology of endometriosis and endometriosis-associated neoplasms. Endometriosis is a chronic inflammatory disease with unknown etiology. Galectins-1, -3 and -9 were found to be overexpressed in ectopic and eutopic endometrium of females with endometriosis compared to those without endometriosis. These findings suggest galectins’ role in the progression on endometriotic lesions and their potential use as diagnostic biomarkers and/or targets for therapeutic approaches. Galectins-1, -3, and -9 have also been implicated in the development of endometriosis-associated neoplasms. Furthermore, galectin-3 has been shown to interact with KRAS protein and contribute to cellular growth, proliferation, inflammation, and the uptake of nutrients in endometriotic lesions and may be involved in the maintenance and propagation of endometriosis. These galectins have been shown to be upregulated in certain forms of cervical, ovarian, endometrial, and colon cancer associated with endometriosis and have become a potential target for anti-cancer therapies.

scholarly journals Mutagenesis and homology modeling reveal a predicted pocket of lysophosphatidylcholine acyltransferase 2 to catch Acyl-CoA

2020 ◽  
Author(s):  
Fumie Hamano ◽  
Kazuaki Matoba ◽  
Tomomi Hashidate-Yoshida ◽  
Tomoyuki Suzuki ◽  
Kiyotake Miura ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Inflammatory Diseases ◽  
Thermotoga Maritima ◽  
Platelet Activating Factor ◽  
Binding Pocket ◽  
New Drugs ◽  
Cellular Functions ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Acyl Coenzyme A

AbstractPlatelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that elicits various cellular functions and promotes several pathological conditions, including anaphylaxis and neuropathic pain. PAF is biosynthesized by two types of lyso-PAF acetyltransferases: lysophosphatidylcholine acyltransferase 1 (LPCAT1) and LPCAT2, which are constitutive and inducible forms of lyso-PAF acetyltransferase, respectively. Because LPCAT2 mainly produces PAF under inflammatory conditions, understanding the structure of LPCAT2 is important for developing specific drugs against PAF-related inflammatory diseases. Although the structure of LPCAT2 has not been determined, the crystal structure was reported for Thermotoga maritima PlsC, an enzyme in the same enzyme family as LPCAT2. In this study, we identified residues in mouse LPCAT2 essential for its enzymatic activity and a potential acyl-coenzyme A (CoA)-binding pocket, based on homology modeling of mouse LPCAT2 with PlsC. We also found that Ala115 of mouse LPCAT2 was important for acyl-CoA selectivity. In conclusion, these results predict the structure of mouse LPCAT2. Our findings have implications for the future development of new drugs against PAF-related diseases.

Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla
Keyword(s):  
Immune Response ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Signalling Molecule ◽  
Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

scholarly journals Senescence under appraisal: hopes and challenges revisited

2021 ◽  
Author(s):  
Camilla S. A. Davan-Wetton ◽  
Emanuela Pessolano ◽  
Mauro Perretti ◽  
Trinidad Montero-Melendez
Keyword(s):  
Cellular Senescence ◽  
Clinical Success ◽  
Immune Surveillance ◽  
Favourable Outcome ◽  
Cellular Growth ◽  
Therapeutic Approaches ◽  
Cycle Arrest ◽  
Therapeutic Development ◽  
The Right ◽  
Inflammation Resolution

AbstractIn recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

scholarly journals Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Perez-Bercoff ◽  
Hélène Laude ◽  
Morgane Lemaire ◽  
Oliver Hunewald ◽  
Valérie Thiers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cell Death ◽  
Lupus Erythematosus ◽  
Immunosuppressive Treatment ◽  
Elevated Serum ◽  
Serum Levels ◽  
Chronic Inflammatory Disease ◽  
Mrna Levels ◽  
Systemic Lupus ◽  
Inflammatory Conditions

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.

scholarly journals Illuminating an Invisible Epidemic: A Systemic Review of the Clinical and Economic Benefits of Early Diagnosis and Treatment in Inflammatory Disease and Related Syndromes

2019 ◽  
Vol 8 (4) ◽  
pp. 493 ◽  
Author(s):  
Wylezinski ◽  
Gray ◽  
Polk ◽  
Harmata ◽  
Spurlock
Keyword(s):  
Healthcare System ◽  
Inflammatory Diseases ◽  
The United States ◽  
Economic Benefits ◽  
Systemic Review ◽  
Best Interest ◽  
Delayed Treatment ◽  
Inflammatory Conditions ◽  
Slow Development ◽  
The U.S

Healthcare expenditures in the United States are growing at an alarming level with the Centers for Medicare and Medicaid Services (CMS) projecting that they will reach $5.7 trillion per year by 2026. Inflammatory diseases and related syndromes are growing in prevalence among Western societies. This growing population that affects close to 60 million people in the U.S. places a significant burden on the healthcare system. Characterized by relatively slow development, these diseases and syndromes prove challenging to diagnose, leading to delayed treatment against the backdrop of inevitable disability progression. Patients require healthcare attention but are initially hidden from clinician’s view by the seemingly generalized, non-specific symptoms. It is imperative to identify and manage these underlying conditions to slow disease progression and reduce the likelihood that costly comorbidities will develop. Enhanced diagnostic criteria coupled with additional technological innovation to identify inflammatory conditions earlier is necessary and in the best interest of all healthcare stakeholders. The current total cost to the U.S. healthcare system is at least $90B dollars annually. Through unique analysis of financial cost drivers, this review identifies opportunities to improve clinical outcomes and help control these disease-related costs by 20% or more.

scholarly journals Comparison of the Essential Cellular Functions of the Two murA Genes of Bacillus anthracis

2008 ◽  
Vol 52 (6) ◽  
pp. 2009-2013 ◽  
Author(s):  
G. C. Kedar ◽  
Vickie Brown-Driver ◽  
Daniel R. Reyes ◽  
Mark T. Hilgers ◽  
Mark A. Stidham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Anthracis ◽  
High Resistance ◽  
Gene Replacement ◽  
Cellular Growth ◽  
Cellular Functions

ABSTRACT Targeted antisense and gene replacement mutagenesis experiments demonstrate that only the murA1 gene and not the murA2 gene is required for the normal cellular growth of Bacillus anthracis. Antisense-based modulation of murA1 gene expression hypersensitizes cells to the MurA-specific antibiotic fosfomycin despite the normally high resistance of B. anthracis to this drug.

Inflammatory and Obstructive Disorders of Salivary Glands

1987 ◽  
Vol 66 (1_suppl) ◽  
pp. 675-679 ◽  
Author(s):  
A. Blitzer
Keyword(s):  
Salivary Glands ◽  
Fine Needle Aspiration ◽  
Chronic Conditions ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Needle Aspiration ◽  
Ct Scans ◽  
Fine Needle ◽  
Inflammatory Conditions ◽  
Chronic Sialadenitis

Obstructive and inflammatory diseases of the salivary glands can have a congenital, traumatic, metabolic, or infectious-inflammatory cause. The acute inflammatory conditions include bacterial and viral infections, and the chronic conditions include sialoliths, strictures, chronic sialadenitis, sialectasis, and lymphoepithelial disease. The neoplastic diseases can cause obstruction and/or infection and often make the diagnosis elusive. In addition to a working knowledge of possible etiology, one needs experience with clinical examination, salivary analysis, sialography, CT scans, MRI, and fine-needle aspiration and cytology in order successfully to evaluate and manage patients with these conditions.

Inflammatory and Obstructive Disorders of Salivary Glands

1987 ◽  
Vol 66 (2_suppl) ◽  
pp. 675-679 ◽  
Author(s):  
A. Blitzer
Keyword(s):  
Salivary Glands ◽  
Fine Needle Aspiration ◽  
Chronic Conditions ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Needle Aspiration ◽  
Ct Scans ◽  
Fine Needle ◽  
Inflammatory Conditions ◽  
Chronic Sialadenitis

Obstructive and inflammatory diseases of the salivary glands can have a congenital, traumatic, metabolic, or infectious-inflammatory cause. The acute inflammatory conditions include bacterial and viral infections, and the chronic conditions include sialoliths, strictures, chronic sialadenitis, sialectasis, and lymphoepithelial disease. The neoplastic diseases can cause obstruction and/or infection and often make the diagnosis elusive. In addition to a working knowledge of possible etiology, one needs experience with clinical examination, salivary analysis, sialography, CT scans, MRI, and fine-needle aspiration and cytology in order successfully to evaluate and manage patients with these conditions.

scholarly journals A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5463-5472 ◽  
Author(s):  
Davide Bagnara ◽  
Matthew S. Kaufman ◽  
Carlo Calissano ◽  
Sonia Marsilio ◽  
Piers E. M. Patten ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Adoptive Transfer ◽  
Severe Combined Immunodeficiency ◽  
Immune Surveillance ◽  
Lymphocytic Leukemia ◽  
Unknown Etiology ◽  
Lymphoid Tissues ◽  
Transfer Model

AbstractChronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity.

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