scholarly journals Crescentic Glomerulonephritis: Pathogenesis and Therapeutic Potential of Human Amniotic Stem Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Ahmed Al Mushafi ◽  
Joshua D. Ooi ◽  
Dragana Odobasic
Keyword(s):  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Immunosuppressive Drugs ◽  
Crescent Formation ◽  
Inflammatory Conditions ◽  
Progressive Type ◽  
Current Therapies ◽  
Excellent Safety Profile ◽  
Human Amniotic Epithelial Cells ◽  
End Stage

Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by glomerular crescent formation. The current therapies for crescentic GN, which consist of broad immunosuppressive drugs, are partially effective, non-specific, toxic and cause many serious side effects including infections, cancer, and cardiovascular problems. Therefore, new and safer therapies are needed. Human amniotic epithelial cells (hAECs) are a type of stem cell which are isolated from the placenta after birth. They represent an attractive and novel therapeutic option for the treatment of various inflammatory conditions owing to their unique and selective immunosuppressive ability, as well as their excellent safety profile and clinical applicability. In this review, we will discuss the immunopathogenesis of crescentic GN, issues with currently available treatments and how hAECs offer potential to become a new and harmless treatment option for this condition.

scholarly journals Renal Allograft Rejection: Noninvasive Ultrasound- and MRI-Based Diagnostics

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ulrich Jehn ◽  
Katharina Schuette-Nuetgen ◽  
Dominik Kentrup ◽  
Verena Hoerr ◽  
Stefan Reuter
Keyword(s):  
Allograft Rejection ◽  
Tissue Sample ◽  
Therapeutic Option ◽  
Immunosuppressive Drugs ◽  
Acute Allograft Rejection ◽  
Noninvasive Diagnostics ◽  
Number Of Patients ◽  
Magnetic Resonance Imaging Mri ◽  
Stage Renal Disease ◽  
End Stage

To date, allogeneic kidney transplantation remains the best available therapeutic option for patients with end-stage renal disease regarding overall survival and quality of life. Despite the advancements in immunosuppressive drugs and protocols, episodes of acute allograft rejection, a sterile inflammatory process, continue to endanger allograft survival. Since effective treatment for acute rejection episodes is available, instant diagnosis of this potentially reversible graft injury is imperative. Although histological examination by invasive core needle biopsy of the graft remains the gold standard for the diagnosis of ongoing rejection, it is always associated with the risk of causing substantial graft injury as a result of the biopsy procedure itself. At the same time, biopsies are not immediately feasible for a considerable number of patients taking anticoagulants due to the high risk of complications such as bleeding and uneven distribution of pathological changes within the graft. This can result in the wrong diagnosis due to the small size of the tissue sample taken. Therefore, there is a need for a tool that overcomes these problems by being noninvasive and capable of assessing the whole organ at the same time for specific and fast detection of acute allograft rejection. In this article, we review current state-of-the-art approaches for noninvasive diagnostics of acute renal transplant inflammation, i.e., rejection. We especially focus on nonradiation-based methods using magnetic resonance imaging (MRI) and ultrasound.

scholarly journals Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders

2020 ◽  
Vol 21 (14) ◽  
pp. 4918
Author(s):  
Swarup Mitra ◽  
Shailesh N. Khatri ◽  
Malabika Maulik ◽  
Abel Bult-Ito ◽  
Marvin Schulte
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Nicotinic Acetylcholine ◽  
Drug Molecules ◽  
Inflammatory Conditions ◽  
Allosteric Sites ◽  
Underlying Mechanisms

Inflammation is a key physiological phenomenon that can be pervasive when dysregulated. Persistent chronic inflammation precedes several pathophysiological conditions forming one of the critical cellular homeostatic checkpoints. With a steady global surge in inflammatory diseases, it is imperative to delineate underlying mechanisms and design suitable drug molecules targeting the cellular partners that mediate and regulate inflammation. Nicotinic acetylcholine receptors have a confirmed role in influencing inflammatory pathways and have been a subject of scientific scrutiny underlying drug development in recent years. Drugs designed to target allosteric sites on the nicotinic acetylcholine receptors present a unique opportunity to unravel the role of the cholinergic system in regulating and restoring inflammatory homeostasis. Such a therapeutic approach holds promise in treating several inflammatory conditions and diseases with inflammation as an underlying pathology. Here, we briefly describe the potential of cholinergic allosterism and some allosteric modulators as a promising therapeutic option for the treatment of neuroinflammation.

scholarly journals The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1212
Author(s):  
Getinet M. Adinew ◽  
Equar Taka ◽  
Patricia Mendonca ◽  
Samia S. Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Option ◽  
Mesenchymal Transition ◽  
Anticancer Effects

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals Inhibition of Xanthine Oxidoreductase Enhances the Potential of Tyrosine Kinase Inhibitors against Chronic Myeloid Leukemia

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 74 ◽  
Author(s):  
Marta Romo-González ◽  
Sara Moreno-Paz ◽  
Violeta García-Hernández ◽  
Fermín Sánchez-Guijo ◽  
Ángel Hernández-Hernández
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Single Agent ◽  
Signaling Cascade ◽  
Xanthine Oxidoreductase

Chronic myeloid leukemia (CML) is characterized by the expression of the oncogenic kinase BCR-ABL. Although tyrosine kinase inhibitors (TKIs) against BCR-ABL represent the standard therapeutic option for CML, resistances to TKIs can be a serious problem. Thus, the search for novel therapeutic approaches is still needed. CML cells show an increased ROS production, which is required for maintaining the BCR-ABL signaling cascade active. In line with that, reducing ROS levels could be an interesting therapeutic strategy for the clinical management of resistant CML. To analyze the therapeutic potential of xanthine oxidoreductase (XOR) in CML, we tested the effect of XOR inhibitor allopurinol. Here, we show for the first time the therapeutic potential of allopurinol against BCR-ABL-positive CML cells. Allopurinol reduces the proliferation and clonogenic ability of the CML model cell lines K562 and KCL22. More importantly, the combination of allopurinol with imatinib or nilotinib reduced cell proliferation in a synergistic manner. Moreover, the co-treatment arms hampered cell clonogenic capacity and induced cell death more strongly than each single-agent arm. The reduction of intracellular ROS levels and the attenuation of the BCR-ABL signaling cascade may explain these effects. Finally, the self-renewal potential of primary bone marrow cells from CML patients was also severely reduced especially by the combination of allopurinol with TKIs. In summary, here we show that XOR inhibition is an interesting therapeutic option for CML, which can enhance the effectiveness of the TKIs currently used in clinics.

Pancreas Allograft Biopsies in the Management of Pancreas Transplant Recipients: Histopathologic Review and Clinical Correlations

2007 ◽  
Vol 131 (8) ◽  
pp. 1192-1199
Author(s):  
Lillian W. Gaber
Keyword(s):  
Pancreas Transplantation ◽  
Therapeutic Option ◽  
Pancreas Transplant ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Systemic Complications ◽  
Histologic Evaluation ◽  
Insulin Dependent ◽  
Pancreas Allograft ◽  
End Stage

Abstract Context.—Pancreas transplantation has become a therapeutic option for patients with type 1 diabetes mellitus who are in end-stage renal failure. It also is indicated for a subset of nonuremic, insulin-dependent diabetics who experience extreme difficulties in maintaining proper glucose homeostasis by insulin therapy that compromises their productivity and safety. Objective.—To provide a review of the literature and expert experiences for understanding the histologic findings in pancreas transplantation. Data Sources.—The published literature between 1990 and 2005 was reviewed for this report. Additionally, personal files of the author were used, along with biopsy slides that were used for figures. Conclusions.—Pancreas transplantation reestablishes the physiologic state of insulin secretion, and pancreas transplant recipients are able to maintain a state of long-term euglycemia and are less likely to be exposed to hyperglycemia and its systemic complications. Key to the success of transplantation is the scrupulous management and close monitoring of the pancreas transplant recipients. To that end, histologic evaluation of pancreas allografts assumed a pivotal role in management of pancreas allograft dysfunction episodes, and in some centers surveillance biopsies are used to monitor immunologically high-risk situations.

Abstract 73: Nanoformulated Copper/Zinc Superoxide Dismutase: Alternative Therapeutic Strategy for Angiotensin II-dependent Neurogenic Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Krupa K Savalia ◽  
Devika S Manickam ◽  
Erin G Rosenbaugh ◽  
Jun Tian ◽  
Iman Ahmad ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Angiotensin Ii ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
In Vivo Studies ◽  
Neuronal Uptake ◽  
Neurogenic Hypertension ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc

Excessive production of superoxide (O2•-) in the central nervous system has been widely implicated in the pathogenesis of angiotensin II (AngII)-dependent neurogenic hypertension (HTN). Our group has tried to overcome the failed therapeutic potential of currently available antioxidants by utilizing nanoformulated copper/zinc superoxide dismutase (SOD1), so-called SOD1 nanozymes, that specifically scavenges intracellular O2•-. These nanozymes consist of SOD1 protein wrapped with cationic block copolymers followed by covalent cross-linking of the polycation template (cl-nano). We hypothesize that cl-nano delivers active SOD1 protein to neurons and can effectively decrease blood pressure in a mouse model of AngII-dependent neurogenic HTN. As determined by electron paramagnetic resonance (EPR) spectroscopy, cl-nano retains SOD1 activity and scavenges O2•- to levels comparable with native SOD1 protein in a cell-free environment (EPR arbitrary units: vehicle 1.12e6 ± 1.79e5; native SOD1 protein 4.45e4 ± 3.00e3; cl-nano 6.78e4 ± 1.74e3, p<0.05 vs. vehicle). Experiments to examine neuronal uptake of cl-nano, analyzed by western blot and SOD1 activity assays, reveal that cl-nano delivers active SOD1 to central neurons in culture (CATH.a neurons) more efficiently than native SOD1 protein following 1 hour treatment (SOD1 activity in units/mg protein: vehicle 336; native SOD1 protein 313; cl-nano 718). Furthermore, in vivo studies demonstrate that HTN established by chronic subcutaneous infusion of AngII (400 ng/kg/min) is significantly attenuated following a single intracerebroventricular (ICV) injection of cl-nano for up to 7 days (mean arterial pressure (MAP) in mmHg: pre-AngII 87 ± 3; 9 days post-AngII 138 ± 6; 7 days post-ICV injection of cl-nano 112 ± 4, p<0.05 vs. pre-ICV injection). These data provide evidence for the efficacy of nanoformulated SOD1 in counteracting excessive O2•- and decreasing MAP in AngII-dependent hypertensive mice when injected directly into the brain. Although further experiments must be performed with more clinically relevant routes of cl-nano administration, such as intravenous injection, this study supports the further development of cl-nano with SOD1 as an alternative therapeutic option for HTN.

scholarly journals Efficacy of adalimumab in moderate to severe hidradenitis suppurativa: Real life data

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Aikaterini Kyriakou ◽  
Anastasia Trigoni ◽  
Nikiforos Galanis ◽  
Dimitrios Sotiriadis ◽  
Aikaterini Patsatsi
Keyword(s):  
Quality Of Life ◽  
Hidradenitis Suppurativa ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Real Life ◽  
Life Quality ◽  
Global Assessment Scale ◽  
Friedman's Test ◽  
Adalimumab Treatment

Hidradenitis suppurativa (HS) is a relapsing, inflammatory disease characterized by painful nodules, abscesses, sinuses track formation and scarring. HS has a great impact on patients’ quality of life and its treatment may be really challenging. Adalimumab provides a new therapeutic option for HS. Our aim was to assess the therapeutic potential of adalimumab on patients with HS based on the data from the daily clinical practice of an HS Outpatient Clinic. 19 patients with clinically evident moderate to severe HS, under adalimumab treatment for at least 24 week, participated in this observational, retrospective study. The Hidradenitis Suppurativa Physician’s Global Assessment scale, Modified Santorius scale and Dermatology Life Quality Index (DLQI) at baseline, week 4, week 12 and week 24 were retrieved from the records. Both Modified Santorius score and DLQI were significantly decreased during the weeks of evaluation (Friedman’s test; P < 0.001). The proportion of patients who achieved clinical response was 10.5% (n = 2) at week 4, 42.1% (n = 8) at week 12 and 63.2% (n = 12) at week 24. Treatment with adalimumab was linked with both clinical remission of HS and improvement of patients’ quality of life.

scholarly journals Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature

2021 ◽  
Vol 8 ◽  
Author(s):  
Per Eriksson ◽  
Johan Mölne ◽  
Lina Wirestam ◽  
Christopher Sjöwall
Keyword(s):  
Ankylosing Spondylitis ◽  
Therapeutic Option ◽  
Relevant Literature ◽  
Acute Phase Reactant ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Beneficial Effects ◽  
Amyloid A ◽  
Inflammatory Conditions

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

scholarly journals Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review

2019 ◽  
Vol 41 (3) ◽  
pp. 427-432 ◽  
Author(s):  
Arbey Aristizabal-Alzate ◽  
John Fredy Nieto-Rios ◽  
Catalina Ocampo-Kohn ◽  
Lina Maria Serna-Higuita ◽  
Diana Carolina Bello-Marquez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Therapeutic Option ◽  
Supportive Therapy ◽  
Hematological Toxicity ◽  
High Morbidity ◽  
Multiple Exchange ◽  
Severe Pancytopenia ◽  
Stage Renal Disease ◽  
End Stage

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.

Sign in / Sign up

Export Citation Format

Share Document