scholarly journals Clostridioides difficile Phage Biology and Application

2021 ◽  
Author(s):  
Joshua Heuler ◽  
Louis-Charles Fortier ◽  
Xingmin Sun
Keyword(s):  
Phage Therapy ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Bacterial Gene ◽  
Healthcare Settings ◽  
Bacterial Gene Expression ◽  
Clostridioides Difficile ◽  
New Treatment ◽  
Further Development ◽  
Insight Into

Abstract Clostridium difficile, now reclassified as Clostridioides difficile, is the causative agent of C. difficile infections (CDI). CDI is particularly challenging in healthcare settings because highly resistant spores of the bacterium can persist in the environment, making it difficult to curb outbreaks. Dysbiosis of the microbiota caused by the use of antibiotics is the primary factor that allows C. difficile to colonize the gut and cause diarrhea and colitis. For this reason, antibiotics targeting C. difficile can be ineffective at preventing recurrent episodes because they exacerbate and prolong dysbiosis. The emergence of antibiotic resistance in C. difficile also presents a significant threat. The diverse array of bacteriophages (phages) that infect C. difficile could offer new treatment strategies and greater insight into the biology of the pathogen. In this review, we summarize the current knowledge regarding C. difficile phages and discuss what is understood about their lifestyles and genomics. Then, we examine how phage infection modifies bacterial gene expression and pathogenicity. Finally, we discuss the potential clinical applications of C. difficile phages such as whole phage therapy and phage-derived products, and we highlight the most promising strategies for further development.

Endometrial Cancer State of the Science Meeting

2009 ◽  
Vol 19 (1) ◽  
pp. 134-140 ◽  
Author(s):  
Henry C. Kitchener ◽  
Edward L. Trimble
Keyword(s):  
Endometrial Cancer ◽  
Current Knowledge ◽  
Gynecological Cancer ◽  
Treatment Strategies ◽  
List Type ◽  
Uterine Carcinosarcoma ◽  
National Cancer Research Institute ◽  
Key Issues ◽  
New Treatment ◽  
State Of The Science

There is a pressing need to improve our understanding of endometrial cancer (EC) and uterine carcinosarcoma and to develop new treatment strategies to improve outcomes. In recognition of this, a State of the Science meeting on EC was held last November 28 and 29, 2006, in Manchester, United Kingdom. The meeting was cosponsored by the National Cancer Research Institute (UK), the National Cancer Institute (US), and the Gynecological Cancer Intergroup.The objectives of the meeting were as follows: To review current knowledge and understanding of EC and its treatments.To identify key issues for translational research and clinical trials.To identify the most important trials for women with endometrial carcinoma and uterine carcinosarcoma, both those already underway or to be done, for which the Gynecological Cancer Intergroup might facilitate international cooperation.

scholarly journals The microenvironment in mature B-cell malignancies: a target for new treatment strategies

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3367-3375 ◽  
Author(s):  
Jan A. Burger ◽  
Paolo Ghia ◽  
Andreas Rosenwald ◽  
Federico Caligaris-Cappio
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
B Cell Malignancies ◽  
Accessory Cells ◽  
Specialized Tissue ◽  
New Treatment ◽  
Novel Strategy ◽  
Secondary Lymphoid Organs

AbstractDespite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.

scholarly journals Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

2021 ◽  
Author(s):  
Joanna Ewa Sowa ◽  
Krzysztof Tokarski
Keyword(s):  
Glial Cells ◽  
Network Effects ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Biased Signaling ◽  
New Treatment

AbstractAccumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

Genomic and genetic aspects of heart failure in dogs — A review

2012 ◽  
Vol 60 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Magdalena Łój ◽  
Magdalena Garncarz ◽  
Michał Jank
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Genetic Markers ◽  
Molecular Pathology ◽  
Treatment Strategies ◽  
Canine Heart ◽  
Common Causes ◽  
Genomic Markers ◽  
New Treatment ◽  
Insight Into

The most common causes of heart failure in dogs are valvular disease, predominantly endocardiosis, and myocardial disease, predominantly dilated cardiomyopathy. They are related to changes in the expression of several genes in the heart muscle and in peripheral blood nuclear cells which could be considered as prognostic or diagnostic markers of heart disease in dogs. Since many human genetic markers of heart failure have turned out to be useless in dogs, the screening for genomic markers of canine heart failure could give more insight into the molecular pathology of these diseases and aid the development of new treatment strategies.

Vitiligo: Mechanisms of Pathogenesis and Treatment

2020 ◽  
Vol 38 (1) ◽  
pp. 621-648 ◽  
Author(s):  
Michael L. Frisoli ◽  
Kingsley Essien ◽  
John E. Harris
Keyword(s):  
T Cells ◽  
Treatment Strategies ◽  
White Spots ◽  
Systemic Treatments ◽  
Ifn Γ ◽  
New Treatment ◽  
Resident Memory T Cells ◽  
Insight Into ◽  
Promote Disease Progression ◽  
Research Studies

Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8+ T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies.

Repurposing auranofin as a Clostridioides difficile therapeutic

2019 ◽  
Author(s):  
Melanie L Hutton ◽  
Havva Pehlivanoglu ◽  
Callum J Vidor ◽  
Meagan L James ◽  
Melanie J Thomson ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Toxin Production ◽  
Spore Production ◽  
Clostridioides Difficile ◽  
New Treatment ◽  
Gut Damage

Abstract Background Clostridioides difficile (previously Clostridium difficile) is the leading cause of nosocomial, antibiotic-associated diarrhoea worldwide. Currently, the gold standard of treatment for C. difficile infection (CDI) is vancomycin or metronidazole, although these antibiotics also perturb the protective resident microbiota, often resulting in disease relapse. Thus, an urgent need remains for the development of new treatment strategies. Auranofin is an FDA-approved oral antirheumatic drug that was previously shown to inhibit C. difficile vegetative cell growth, toxin production and spore production in vitro. Objectives To determine the efficacy of auranofin as a CDI therapeutic by examining the effect of treatment on toxin and spore production in vitro and in vivo, and on disease outcomes in mice. Methods C. difficile cultures were treated with auranofin and examined for effects on sporulation and toxin production by sporulation assay and ELISA, respectively. Mice were pretreated with auranofin prior to infection with C. difficile and monitored for physiological conditions, survival and gut damage compared with control animals. Faeces from mice were analysed to determine whether auranofin reduces sporulation and toxin production in vivo. Results Auranofin significantly reduces sporulation and toxin production under in vitro conditions and in infected mice in vivo. Mice treated with auranofin lost less weight, displayed a significant increase in survival rates and had significantly less toxin-mediated damage in their colon and caecum compared with control mice. Conclusions Auranofin shows promise as a prospective therapeutic option for C. difficile infections.

scholarly journals Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 131
Author(s):  
Christian Kranjec ◽  
Danae Morales Angeles ◽  
Marita Torrissen Mårli ◽  
Lucía Fernández ◽  
Pilar García ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Treatment Strategies ◽  
Extracellular Dna ◽  
Human Immune System ◽  
Antibiotic Resistant ◽  
New Treatment ◽  
Biofilm Development ◽  
Hospital Acquired

Staphylococci, like Staphylococcus aureus and S. epidermidis, are common colonizers of the human microbiota. While being harmless in many cases, many virulence factors result in them being opportunistic pathogens and one of the major causes of hospital-acquired infections worldwide. One of these virulence factors is the ability to form biofilms—three-dimensional communities of microorganisms embedded in an extracellular polymeric matrix (EPS). The EPS is composed of polysaccharides, proteins and extracellular DNA, and is finely regulated in response to environmental conditions. This structured environment protects the embedded bacteria from the human immune system and decreases their susceptibility to antimicrobials, making infections caused by staphylococci particularly difficult to treat. With the rise of antibiotic-resistant staphylococci, together with difficulty in removing biofilms, there is a great need for new treatment strategies. The purpose of this review is to provide an overview of our current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms. Furthermore, we look into promising targets and therapeutic methods, including bacteriocins and phage-derived antibiofilm approaches.

scholarly journals Impact of Cancer Stem Cells and Cancer Stem Cell-Driven Drug Resiliency in Lung Tumor: Options in Sight

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 267
Author(s):  
Lourdes Cortes-Dericks ◽  
Domenico Galetta
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lung Tumor ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Resistant Cell ◽  
New Treatment ◽  
Efficient Elimination

Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.

scholarly journals A Crucial Role for Ergosterol in Plasma Membrane Composition, Localisation, and Activity of Cdr1p and H+-ATPase in Candida albicans

2019 ◽  
Vol 7 (10) ◽  
pp. 378 ◽  
Author(s):  
Jakub Suchodolski ◽  
Jakub Muraszko ◽  
Przemysław Bernat ◽  
Anna Krasowska
Keyword(s):  
Candida Albicans ◽  
Plasma Membrane ◽  
Efflux Pump ◽  
Treatment Strategies ◽  
Membrane Composition ◽  
Vacuole Fusion ◽  
Increased Sensitivity ◽  
Opportunistic Fungal Pathogen ◽  
New Treatment ◽  
Insight Into

Candida albicans is an opportunistic fungal pathogen of humans. Treatment of C. albicans infections relies on azoles, which target the lanosterol 14α-demethylase (Erg11p) encoded by the ERG11 gene. Our results show that targeted gene disruption of ERG11 can result in resistance to ergosterol-dependent drugs (azoles and amphotericin B), auxotrophy and aerobically viable erg11Δ/Δ cells. Abnormal sterol deposition and lack of ergosterol in the erg11Δ/Δ strain leads to reduced plasma membrane (PM) fluidity, as well as dysfunction of the vacuolar and mitochondrial membranes, resulting respectively in defects in vacuole fusion and a reduced intracellular ATP level. The altered PM structure of the erg11Δ/Δ strain contributes to delocalisation of H+-ATPase and the Cdr1 efflux pump from the PM to vacuoles and, resulting in a decrease in PM potential (Δψ) and increased sensitivity to ergosterol-independent xenobiotics. This new insight into intracellular processes under Erg11p inhibition may lead to a better understanding of the indirect effects of azoles on C. albicans cells and the development of new treatment strategies for resistant infections.

Nucleosome dynamics

2006 ◽  
Vol 73 ◽  
pp. 109-119 ◽  
Author(s):  
Chris Stockdale ◽  
Michael Bruno ◽  
Helder Ferreira ◽  
Elisa Garcia-Wilson ◽  
Nicola Wiechens ◽  
...  
Keyword(s):  
High Resolution ◽  
Chromatin Structure ◽  
Current Knowledge ◽  
Dynamic Properties ◽  
Structure And Dynamics ◽  
Nucleosome Dynamics ◽  
Sharp Focus ◽  
Recent Advances ◽  
Insight Into ◽  
Chromatin Structure And Dynamics

In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Here, recent advances in the understanding of chromatin structure and dynamics are highlighted. The ways in which different modes of nucleosome reconfiguration are likely to influence each other are discussed, and some of the factors likely to regulate the dynamic properties of nucleosomes are considered.

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