scholarly journals Niclosamide suppresses macrophage-induced inflammation in endometriosis†

2020 ◽  
Vol 102 (5) ◽  
pp. 1011-1019 ◽  
Author(s):  
Nikola Sekulovski ◽  
Allison E Whorton ◽  
Tomoki Tanaka ◽  
Yasushi Hirota ◽  
Mingxin Shi ◽  
...  
Keyword(s):  
Cell Viability ◽  
Stromal Cells ◽  
Human Peripheral Blood ◽  
Treatment Options ◽  
Current Treatment ◽  
Reproductive Age ◽  
Cytokines And Chemokines ◽  
Secreted Factors ◽  
Limited Efficacy ◽  
Gynecological Disease

Abstract Endometriosis is a common gynecological disease, which causes chronic pelvic pain and infertility in women of reproductive age. Due to limited efficacy of current treatment options, a critical need exists to develop new and effective treatments for endometriosis. Niclosamide is an efficacious and FDA-approved drug for the treatment of helminthosis in humans that has been used for decades. We have reported that niclosamide reduces growth and progression of endometriosis-like lesions via targeting STAT3 and NFĸB signaling in a mouse model of endometriosis. To examine the effects of niclosamide on macrophage-induced inflammation in endometriosis, a total of 29 stage III–IV endometrioma samples were used to isolate human endometriotic stromal cells (hESCs). M1 or M2 macrophages were isolated and differentiated from fresh human peripheral blood samples. Then, hESCs were cultured in conditioned media (CM) from macrophages with/without niclosamide. Niclosamide dose dependently reduced cell viability and the activity of STAT3 and NFκB signaling in hESCs. While macrophage CM stimulated cell viability in hESCs, niclosamide inhibited this stimulation. Macrophage CM stimulated the secretion of proinflammatory cytokines and chemokines from hESCs. Most of these secreted factors were inhibited by niclosamide. These results indicate that niclosamide is able to reduce macrophage-induced cell viability and cytokine/chemokine secretion in hESCs by inhibiting inflammatory mechanisms via STAT3 and/or NFκB signaling.

scholarly journals Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Induces Apoptosis of Human Endometriotic Cells through Suppression of ERK1/2, AKT, NFκB and β-CATENIN Pathways and Activation of Intrinsic Apoptotic Mechanisms

2009 ◽  
Vol 94 (7) ◽  
pp. 2673-2673
Author(s):  
Sakhila K. Banu ◽  
JeHoon Lee ◽  
V. O. Speights ◽  
Anna Starzinski-Powitz ◽  
Joe A. Arosh
Keyword(s):  
Prostaglandin E2 ◽  
Treatment Options ◽  
Uterine Cavity ◽  
Selective Inhibition ◽  
Current Treatment ◽  
Reproductive Age ◽  
Treatment Modalities ◽  
Migration And Invasion ◽  
Antiapoptotic Proteins ◽  
Apoptotic Pathways

Endometriosis is a benign chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, reproductive health of women, and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration and invasion of human endometriotic epithelial and stromal cells which was due to decreased PGE2 production. In this study, we determined mechanisms through which prostaglandin E2 (PGE2) promoted survival of human endometriotic cells. Results of the present study indicate that: (i) PGE2 promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, NFκB, and β-catenin signaling pathways; (ii) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome C and thus activates caspase-3/PARP-mediated intrinsic apoptotic pathways; and (iii) these PGE2 signaling components are more abundantly expressed in ectopic endometriosis tissues compared to eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including non-estrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

scholarly journals Systemic Lupus Erythematosus Treatment in Pregnancy: Case Study

2020 ◽  
Vol 20 (2) ◽  
pp. 80-89
Author(s):  
Z Laucekova ◽  
K Biskupska Bodova ◽  
M Nachajova ◽  
E Kudela ◽  
R Fiolka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Current Treatment ◽  
Reproductive Age ◽  
Management Approach ◽  
Systemic Lupus ◽  
High Prevalence ◽  
Life Threatening ◽  
Inflammatory Autoimmune Disease

AbstractSystemic lupus erythematosus is a chronic inflammatory autoimmune disease with high prevalence in female in reproductive age. In recent years the prognosis of pregnant patients with SLE has improved significantly. Even though the treatment options have improved, the risk of flares, preeclampsia, pregnancy loss, and premature labours remains high compared to healthy women. The aim of this article is to offer a review of current treatment options in pregnant patients with SLE and to present a case report of 32-year-old patient with newly diagnosed acute outbreak of SLE, who experienced a life-threatening multisystem flare at 24 weeks of gestational age. This case represents one of the most extreme manifestations of lupus disease activity associated with pregnancy that has been reported in literature and emphasizes the importance of preconception evaluation and counseling and amultidisciplinary management approach in cases with a complex and evolving clinical course.

scholarly journals Long Non-Coding RNA ADAMTS9-AS1 Represses Ferroptosis of Endometrial Stromal Cells Through Regulating miR-6516-5p/GPX4 Axis in Endometriosis

2021 ◽  
Author(s):  
Yiting Wan ◽  
Cancan Gu ◽  
Jueying Kong ◽  
Jin Sui ◽  
Ling Zuo ◽  
...  
Keyword(s):  
Cell Viability ◽  
Stromal Cells ◽  
Underlying Mechanism ◽  
Current Data ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Aberrant Expression ◽  
Non Coding Rna ◽  
And Migration ◽  
Proliferation And Migration

Abstract Endometriosis (EMs) is one of the most frequent diseases in reproductive age women, characterized by the growth of endometrial tissues beyond the uterus. Enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) is the major cause of EMs. Mounting studies have demonstrated that long non-coding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), here we investigated the biological effect of ADAMTS9-AS1 on ESCs proliferation and migration and explored the underlying mechanism. The current data showed that the ADAMTS9-AS1 expression was significantly up-regulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More important, the effect of ADAMTS9-AS1 inhibition on decreasing ESCs viability was significantly blocked by Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed Erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) level and malonyl dialdehyde (MDA) content, and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) via sponging miR-6516-5p to de-repress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that up-regulated ADAMTS9-AS1 accelerates ESCs proliferation and migration through regulating miR-6516-5p/GPX4-dependent ferroptosis, and may be a potential target for the treatment of EMs.

An Overview of Dementias

2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Current Treatment ◽  
Great Variability ◽  
Health Concern ◽  
Public Health Concern ◽  
Life Threatening ◽  
The Common ◽  
Neurodegenerative Dementias ◽  
Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

Initiation of Clozapine Therapy in a Patient With Preexisting Leukopenia: A Discussion of the Rationale of Current Treatment Options

2001 ◽  
Vol 13 (4) ◽  
pp. 233-237 ◽  
Author(s):  
Roger Boshes ◽  
Theo Manschreck ◽  
Jean Desrosiers ◽  
Steven Candela ◽  
Meredith Hanrahan-Boshes
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
Clozapine Therapy

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Stew in its Own Juice: Protein Homeostasis Machinery Inhibition Reduces Cell Viability in Multiple Myeloma Cell Lines

2019 ◽  
Vol 19 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Mariana B. de Oliveira ◽  
Luiz F.G. Sanson ◽  
Angela I.P. Eugenio ◽  
Rebecca S.S. Barbosa-Dantas ◽  
Gisele W.B. Colleoni
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Viability ◽  
Cell Lines ◽  
Treatment Options ◽  
Compensatory Mechanism ◽  
Protein Homeostasis ◽  
Protein Response ◽  
Rpmi 8226

Introduction:Multiple myeloma (MM) cells accumulate in the bone marrow and produce enormous quantities of immunoglobulins, causing endoplasmatic reticulum stress and activation of protein handling machinery, such as heat shock protein response, autophagy and unfolded protein response (UPR).Methods:We evaluated cell lines viability after treatment with bortezomib (B) in combination with HSP70 (VER-15508) and autophagy (SBI-0206965) or UPR (STF- 083010) inhibitors.Results:For RPMI-8226, after 72 hours of treatment with B+VER+STF or B+VER+SBI, we observed 15% of viable cells, but treatment with B alone was better (90% of cell death). For U266, treatment with B+VER+STF or with B+VER+SBI for 72 hours resulted in 20% of cell viability and both treatments were better than treatment with B alone (40% of cell death). After both triplet combinations, RPMI-8226 and U266 presented the overexpression of XBP-1 UPR protein, suggesting that it is acting as a compensatory mechanism, in an attempt of the cell to handle the otherwise lethal large amount of immunoglobulin overload.Conclusion:Our in vitro results provide additional evidence that combinations of protein homeostasis inhibitors might be explored as treatment options for MM.

scholarly journals Role of Dendritic Cell in Diabetic Nephropathy

2021 ◽  
Vol 22 (14) ◽  
pp. 7554
Author(s):  
Hyunwoo Kim ◽  
Miyeon Kim ◽  
Hwa-Young Lee ◽  
Ho-Young Park ◽  
Hyunjhung Jhun ◽  
...  
Keyword(s):  
T Cells ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Renal Tissue ◽  
Current Treatment ◽  
Diabetic Patients ◽  
Activated T Cells ◽  
Stage Renal Disease ◽  
Incident Cases

Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.

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