scholarly journals Immunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives

2018 ◽  
Vol 4 (4) ◽  
pp. 137 ◽  
Author(s):  
Chris Lauruschkat ◽  
Hermann Einsele ◽  
Juergen Loeffler
Keyword(s):  
Immune Cell ◽  
Current Knowledge ◽  
Antifungal Drugs ◽  
Current Status ◽  
Remission Induction ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Broad Variety ◽  
Immunological Recovery

Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various improvements that have been made with preventative strategies and the development of antifungal drugs, there is an urgent need for new therapeutic approaches that focus on strategies to boost the host’s immune response, since immunological recovery is recognized as being the major determinant of the outcome of IA. Here, we aim to summarize current knowledge about a broad variety of immunotherapeutic approaches against IA, including therapies based on the transfer of distinct immune cell populations, and the administration of cytokines and antibodies.

scholarly journals CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diagnostic Methods ◽  
Opportunistic Pathogens ◽  
Yeast Infection ◽  
Life Threatening ◽  
Therapeutic Alternatives

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.

scholarly journals Two Faces of TGF-Beta1 in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Clinical Investigation ◽  
Mesenchymal Transition ◽  
Early Stages ◽  
New Therapeutic Approaches ◽  
Genes Encoding ◽  
Life Threatening

Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation.

scholarly journals Approach to Hemoptysis in the Modern Era

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Sébastien Gagnon ◽  
Nicholas Quigley ◽  
Hervé Dutau ◽  
Antoine Delage ◽  
Marc Fortin
Keyword(s):  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Regenerated Cellulose ◽  
Therapeutic Approaches ◽  
Antifibrinolytic Agents ◽  
Endoscopic Techniques ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Diagnostic Modalities ◽  
Modern Era

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.

scholarly journals Histone Deacetylases in the Inflamed Intestinal Epithelium—Promises of New Therapeutic Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenz Gerbeth ◽  
Rainer Glauben
Keyword(s):  
Cell Signaling ◽  
Intestinal Epithelium ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Inflammatory Conditions

The intestinal epithelium is a complex, dynamic barrier that separates luminal contents from the immune compartment while mediating nutrient absorption and controlled passage of antigens to convey oral tolerance. A compromised epithelial barrier often leads to inflammation because immune cells in the lamina propria come into direct contact with luminal antigens. Defects in epithelial cell function were also shown to be involved in the etiology of inflammatory bowel diseases. These are severe, chronically relapsing inflammatory conditions of the gastrointestinal tract that also increase the risk of developing colorectal cancer. Despite major efforts of the scientific community, the precise causes and drivers of these conditions still remain largely obscured impeding the development of a permanent cure. Current therapeutic approaches mostly focus on alleviating symptoms by targeting immune cell signaling. The protein family of histone deacetylases (HDACs) has gained increasing attention over the last years, as HDAC inhibitors were shown to be potent tumor cell suppressors and also alleviate morbid inflammatory responses. Recent research continuously identifies new roles for specific HDACs suggesting that HDACs influence the cell signaling network from many different angles. This makes HDACs very interesting targets for therapeutic approaches but predicting effects after system manipulations can be difficult. In this review, we want to provide a comprehensive overview of current knowledge about the individual roles of HDACs in the intestinal epithelium to evaluate their therapeutic potential for inflammatory conditions of the gut.

scholarly journals Photopheresis efficacy in the treatment of rheumatoid arthritis: a pre-clinical proof of concept

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Céline Coppard ◽  
Francis Bonnefoy ◽  
Dalil Hannani ◽  
Françoise Gabert ◽  
Olivier Manches ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cell ◽  
Unmet Need ◽  
Proof Of Concept ◽  
Therapeutic Approaches ◽  
Spleen Cells ◽  
New Therapeutic Approaches ◽  
Bovine Collagen ◽  
Treated Sample ◽  
Immune Cell Subsets

Abstract Background Despite major advances in rheumatoid arthritis outcome, not all patients achieve remission, and there is still an unmet need for new therapeutic approaches. This study aimed at evaluating in a pre-clinical murine model the efficacy of extracorporeal photopheresis (ECP) in the treatment of rheumatoid arthritis, and to provide a relevant study model for dissecting ECP mechanism of action in autoimmune diseases. Methods DBA/1 mice were immunized by subcutaneous injection of bovine collagen type II, in order to initiate the development of collagen-induced arthritis (CIA). Arthritic mice received 3 ECP treatments every other day, with psoralen + UVA-treated (PUVA) spleen cells obtained from arthritic mice. Arthritis score was measured, and immune cell subsets were monitored. Results ECP-treated mice recovered from arthritis as evidenced by a decreasing arthritic score over time. Significant decrease in the frequency of Th17 cells in the spleen of treated mice was observed. Interestingly, while PUVA-treated spleen cells from healthy mouse had no effect, PUVA-treated arthritic mouse derived-spleen cells were able to induce control of arthritis development. Conclusions Our results demonstrate that ECP can control arthritis in CIA-mice, and clarifies ECP mechanisms of action, showing ECP efficacy and Th17 decrease only when arthritogenic T cells are contained within the treated sample. These data represent a pre-clinical proof of concept supporting the use of ECP in the treatment of RA in Human.

scholarly journals Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate

mBio ◽  
2021 ◽  
Author(s):  
Kimberly K. Kajihara ◽  
Homer Pantua ◽  
Hilda Hernandez-Barry ◽  
Meredith Hazen ◽  
Kiran Deshmukh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Clinical Success ◽  
Therapeutic Approaches ◽  
Preclinical Stage ◽  
Content Type ◽  
New Therapeutic Approaches ◽  
Life Threatening

Antibiotic treatment of life-threatening P. aeruginosa infections is associated with low clinical success, despite the availability of antibiotics that are active in standard microbiological in vitro assays, affirming the need for new therapeutic approaches. Antibiotics often fail in the preclinical stage due to insufficient efficacy against P. aeruginosa .

Poly(ADP-Ribose) Polymerase-1 Inhibitors Drug Discovery, Design, and Development as Anticancer Agents from Past to Present: A Mini-Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Arwa AlGhamdi ◽  
Hanine AlMubayedh
Keyword(s):  
Anticancer Agents ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Therapeutic Approaches ◽  
Repair Mechanism ◽  
Design And Development ◽  
Cancer Treatments ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Cancerous Cells

Abstract: Cancer treatments are known for their life-threatening toxicities attributed to their low selectivity; hence, new therapeutic approaches are being developed as alternatives. Among those approaches is the DNA repair mechanism, where its inhibition results selectively in the death of cancerous cells. Poly(ADP-Ribose) Polymerase (PARP) is one of the enzymes involved in the repair of damaged DNA. The inhibition of PARP shows to be a promising approach for effective targeted treatment of cancer, especially in tumours with pre-existing Homologous-Repair (HR) defects (i.e., BRCA). Nicotinamide, which is one of the PARP catalytic products, was the first identified PARP inhibitor (PARPi). The first FDA-approved PARPi was Olaparib in 2014 for the treatment of BRCA mutated advanced ovarian cancer. Several clinical trials have been conducted to further improve PARPi. However, there are some concerns related to drug resistance, PARPi sensitive-tumour identification, and toxic accumulation of PARPi. This report will review the uses of PARPi, drug design and development of PARPi from past to present, current issues, and prospective plans.

scholarly journals Distinct Roles of ROCK1 and ROCK2 on the Cerebral Ischemia Injury and Subsequently Neurodegenerative Changes

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 3-8 ◽  
Author(s):  
Weizhuo Lu ◽  
Jiyue Wen ◽  
Zhiwu Chen
Keyword(s):  
Cerebral Ischemia ◽  
Axonal Regeneration ◽  
Current Knowledge ◽  
Rho Kinase ◽  
Synaptic Function ◽  
Cerebral Injury ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Promising Target ◽  
Cerebral Ischemic

Cerebral ischemic injury is one of the main causes of adult disability and death. Although significant progress has been made, cerebral ischemia continues to be a major risk to public health worldwide. The Rho kinase (ROCK) signaling pathway has been reported to be significantly involved in many mechanisms of cerebral injury. Although ROCK is ubiquitously expressed in all tissues, ROCK2 subtype expression in brain and the spinal cord is more abundant and improves with age. This makes it a promising target for new therapeutic approaches. In this article, we review the current knowledge on the involvement of ROCK in cerebral ischemia injury and neurodegenerative changes after cerebral injury. After a detailed description of the mechanism of ROCK involvement in axonal regeneration and synaptic function, different roles of ROCK1 and ROCK2 in neurons under physiological and pathological conditions are compared and discussed. In addition, different functions of genetic and pharmacological inhibitions of ROCK1 and ROCK2 on cerebral injury are discussed.

scholarly journals New therapeutic approaches of mesenchymal stem cells-derived exosomes

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jana Janockova ◽  
Lucia Slovinska ◽  
Denisa Harvanova ◽  
Timea Spakova ◽  
Jan Rosocha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Experimental Models ◽  
Target Cells ◽  
Therapeutic Approaches ◽  
Paracrine Factors ◽  
New Therapeutic Approaches ◽  
Cell Based Therapy

AbstractMesenchymal stem cells (MSCs) have been demonstrated to have a great potential in the treatment of several diseases due to their differentiation and immunomodulatory capabilities and their ability to be easily cultured and manipulated. Recent investigations revealed that their therapeutic effect is largely mediated by the secretion of paracrine factors including exosomes. Exosomes reflect biophysical features of MSCs and are considered more effective than MSCs themselves. Alternative approaches based on MSC-derived exosomes can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy. Furthermore, MSC-derived exosomes may provide a potent therapeutic strategy for various diseases and are promising candidates for cell-based and cell-free regenerative medicine. This review briefly summarizes the development of MSCs as a treatment for human diseases as well as describes our current knowledge about exosomes: their biogenesis and molecular composition, and how they exert their effects on target cells. Particularly, the therapeutic potential of MSC-derived exosomes in experimental models and recent clinical trials to evaluate their safety and efficacy are summarized in this study. Overall, this paper provides a current overview of exosomes as a new cell-free therapeutic agent.

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