Host-directed Therapy Against Tuberculosis Through Targeting Eicosanoid Pathway Key Enzymes PDF Download
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Author: Wenfei Wang
Publisher:
ISBN:
Category :
Languages : de
Pages : 0
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Book Description
Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis (TB), remains a significant global public health burden. The limitations of traditional antimycobacterial therapies led researchers in the tuberculosis community to focus on the possibility of modulating the host immune response as adjunctive therapy. We identified a genetic variation (rs8193036) in the promoter region of IL17A is associated with susceptibility to TB. Functional assay demonstrated that rs8193036 C allele exhibited significantly lower promotor transcription activities. The rs13120371 AA genotype was strongly associated with an increased risk of TB and increased xCT mRNA expression levels compared to those with the GG or AG genotype. rs13120371 is located on the 3' untranslated (UTR) region of the xCT gene, the rs13120371 AA genotype inhibited the binding of miR-42-3p to xCT. Pretreatment with sulfasalazine (SASP) alleviated bacterial burden in cells with the AA genotype but conferred no benefit in cells with the GG phenotype. We found that the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES)-1 increased significantly in monocyte-derived macrophages (MDM) which the infected M.tb still alive. After treatment with SASP, COX-2 gene expression and the level of PGE2 decreased to normal level. COX-2 might be a novel target for treatment of TB and that SASP might be a potential therapeutic drug which prevents severe inflammation in the pathogenesis process of TB. Together, this thesis provides evidence that infection of human macrophages by M.tb strongly induces eicosanoid pathway key enzyme expression along with pro-inflammatory cytokine formation, which is suppressed by SASP that facilitates M.tb clearance by macrophages. The repurposing of already available drugs known to modulate host responses may improve the future of host directed therapy (HDT) for TB.
Author: Wenfei Wang
Publisher:
ISBN:
Category :
Languages : de
Pages : 0
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Book Description
Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis (TB), remains a significant global public health burden. The limitations of traditional antimycobacterial therapies led researchers in the tuberculosis community to focus on the possibility of modulating the host immune response as adjunctive therapy. We identified a genetic variation (rs8193036) in the promoter region of IL17A is associated with susceptibility to TB. Functional assay demonstrated that rs8193036 C allele exhibited significantly lower promotor transcription activities. The rs13120371 AA genotype was strongly associated with an increased risk of TB and increased xCT mRNA expression levels compared to those with the GG or AG genotype. rs13120371 is located on the 3' untranslated (UTR) region of the xCT gene, the rs13120371 AA genotype inhibited the binding of miR-42-3p to xCT. Pretreatment with sulfasalazine (SASP) alleviated bacterial burden in cells with the AA genotype but conferred no benefit in cells with the GG phenotype. We found that the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES)-1 increased significantly in monocyte-derived macrophages (MDM) which the infected M.tb still alive. After treatment with SASP, COX-2 gene expression and the level of PGE2 decreased to normal level. COX-2 might be a novel target for treatment of TB and that SASP might be a potential therapeutic drug which prevents severe inflammation in the pathogenesis process of TB. Together, this thesis provides evidence that infection of human macrophages by M.tb strongly induces eicosanoid pathway key enzyme expression along with pro-inflammatory cytokine formation, which is suppressed by SASP that facilitates M.tb clearance by macrophages. The repurposing of already available drugs known to modulate host responses may improve the future of host directed therapy (HDT) for TB.
Author: Petros C. Karakousis
Publisher: Springer Nature
ISBN: 3030569055
Category : Medical
Languages : en
Pages : 325
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Book Description
This book discusses specific immune cell regulatory pathway(s), immune cell types, or other mechanisms involved in host responses to tuberculosis that can be potentially targeted for host-directed therapy (HDT). The pathways/mechanisms investigated are either protective – thus calling for pathway/factor enhancing drugs – or maladaptive – thus calling for pathway/factor inhibitory drugs. Discovery and development (pre-clinical and clinical) of candidate HDT agents will also be elucidated, as well as approaches for HDT of other diseases. The benefit to the reader will derive from learning about the biology of multiple host pathways involved in health and disease, how these pathways are disrupted or dysregulated during tuberculosis, and which druggable targets exist in these pathways. This book provides the reader with a roadmap of current and future directions of HDT against tuberculosis. Since the host pathways/factors involved in protective or maladaptive responses to tuberculosis are not disease-specific, information learned from the context of tuberculosis likely will be relevant to other infectious and non-infectious diseases.
Author: Bharat B. Aggarwal
Publisher: Springer
ISBN: 3034808372
Category : Medical
Languages : en
Pages : 489
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Book Description
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Author: Terry B. Strom
Publisher: Wiley-Blackwell
ISBN: 9780632043590
Category : Medical
Languages : en
Pages : 672
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Book Description
Therapeutic Immunology is a comprehensive review of the clinical application of the drugs, biologic agents, and procedures used to treat immunologic diseases. It is the only reference that provides current information on antibodies, cytokines, gene and cell therapies, vaccines, and other therapeutic approaches in the managament of immune system disorders. This book will show how immunology has come of age as a clinical discipline and is now able to provide treatment strategies for many previously incurable diseases.
Author: Geanncarlo Lugo-Villarino
Publisher: Frontiers Media SA
ISBN: 2889630579
Category :
Languages : en
Pages : 790
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Book Description
The Mononuclear Phagocyte System (MPS) of vertebrates is composed of monocytes, macrophages and dendritic cells. Together, they form part of the first line of immune defense against a variety of pathogens (bacteria, fungi, parasites and viruses), and thus play an important role in maintaining organism homeostasis. The mode of transmission, type of replication and mechanism of disease-causing differ significantly for each pathogen, eliciting a unique immune response in the host. Within this context, the MPS acts as both the sentinel and tailor of the immune system. As sentinels, MPS cells are found in blood and within tissues throughout the body to patrol against pathogenic insult. The strategy to detect 'microbial non-self' relies on MPS to recognize conserved microbial products known as 'pathogen-associated molecular pattern' (PAMPs). PAMPs recognition represents a checkpoint in the response to pathogens and relies on conserved 'pattern recognition receptors' (PRRs). Upon PRR engagement, MPS mount a cell-autonomous attack that includes the internalization and compartmentalization of intracellular pathogens into toxic compartments that promote destruction. In parallel, MPS cells launch an inflammatory response composed of a cellular arm and soluble factors to control extracellular pathogens. In cases when innate immunity fails to eliminate the invading microbe, MPS serves as a tailor to generate adaptive immunity for pathogen eradication and generation of "memory" cells, thus ensuring enhanced protection against re-infection. Indeed, MPS cell functions comprise the capture, process, migration and delivery of antigenic information to lymphoid organs, where type-1 immunity is tailored against intracellular microbes and type-2 immunity against extracellular pathogens. However, this potent adaptive immunity is also a double-edge sword that can cause aberrant inflammatory disorders, like autoimmunity or chronic inflammation. For this reason, MPS also tailors tolerance immunity against unwanted inflammation. Successful clearance of the microbe results in its destruction and proper collection of debris, resolution of inflammation and tissue healing for which MPS is essential. Reciprocally, as part of the evolutionary process taking place in all organisms, microbes evolved strategies to circumvent the actions bestowed by MPS cells. Multiple pathogens modulate the differentiation, maturation and activation programs of the MPS, as an efficient strategy to avoid a dedicated immune response. Among the most common evasion strategies are the subversion of phagocytosis, inhibition of PRR-mediated immunity, resistance to intracellular killing by reactive oxygen and nitrogen species, restriction of phagosome maturation, modulation of cellular metabolism and nutrient acquisition, regulation of cell death and autophagy, and modulation of pro-inflammatory responses and hijacking of tolerance mechanisms, among others. The tenet of this eBook is that a better understanding of MPS in infection will yield insights for development of therapeutics to enhance antimicrobial processes or dampen detrimental inflammation for the host's benefit. We believe that contributions to this topic will serve as a platform for discussion and debate about relevant issues and themes in this field. Our aim is to bring expert junior and senior scientists to address recent progress, highlight critical knowledge gaps, foment scientific exchange, and establish conceptual frameworks for future MPS investigation in the context of infectious disease.
Author: Waliza Ansar
Publisher: Springer
ISBN: 8132226801
Category : Medical
Languages : en
Pages : 324
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Book Description
This book offers a comprehensive study of C-reactive protein (CRP) belonging to the pentraxin family, including a brief history of CRP, its structure, synthesis and evolution. Focusing on the emerging role of CRP and its clinical application in the field of disease biology, it details the pathophysiological role of CRP in a host of diseases such as cardiovascular disease, diabetes, cancers, rheumatoid arthritis and infectious diseases and others. It also discusses the role of innate immunity and acute phase response (APR) and their key mediators in the host body in response to tissue injury, infection, trauma or surgery, immunological disorders or neoplastic growth. CRP’s significance in inflammation is highlighted, and its importance as a clinical marker in cardiovascular disease, its functional significance in Leishmania and Plasmodium infections, its association with the development of insulin resistance in type 2 diabetes mellitus, and its role in cancer are discussed in detail. The book also includes clinical data studies and presents the latest research advances to further readers’ understanding of CRP.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309173183
Category : Medical
Languages : en
Pages : 722
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Book Description
Every aspect of immune function and host defense is dependent upon a proper supply and balance of nutrients. Severe malnutrition can cause significant alteration in immune response, but even subclinical deficits may be associated with an impaired immune response, and an increased risk of infection. Infectious diseases have accounted for more off-duty days during major wars than combat wounds or nonbattle injuries. Combined stressors may reduce the normal ability of soldiers to resist pathogens, increase their susceptibility to biological warfare agents, and reduce the effectiveness of vaccines intended to protect them. There is also a concern with the inappropriate use of dietary supplements. This book, one of a series, examines the impact of various types of stressors and the role of specific dietary nutrients in maintaining immune function of military personnel in the field. It reviews the impact of compromised nutrition status on immune function; the interaction of health, exercise, and stress (both physical and psychological) in immune function; and the role of nutritional supplements and newer biotechnology methods reported to enhance immune function. The first part of the book contains the committee's workshop summary and evaluation of ongoing research by Army scientists on immune status in special forces troops, responses to the Army's questions, conclusions, and recommendations. The rest of the book contains papers contributed by workshop speakers, grouped under such broad topics as an introduction to what is known about immune function, the assessment of immune function, the effect of nutrition, and the relation between the many and varied stresses encountered by military personnel and their effect on health.
Author: Glenn Fuller
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 392
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Book Description
Author: Robert Schleip
Publisher: Elsevier Health Sciences
ISBN: 0702052280
Category : Medical
Languages : en
Pages : 566
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Book Description
This book is the product of an important collaboration between clinicians of the manual therapies and scientists in several disciplines that grew out of the three recent International Fascia Research Congresses (Boston, Amsterdam, and Vancouver). The book editors, Thomas Findley MD PhD, Robert Schleip PhD, Peter Huijing PhD and Leon Chaitow DO, were major organizers of these congresses and used their extensive experience to select chapters and contributors for this book. This volume therefore brings together contributors from diverse backgrounds who share the desire to bridge the gap between theory and practice in our current knowledge of the fascia and goes beyond the 2007, 2009 and 2012 congresses to define the state-of-the-art, from both the clinical and scientific perspective. Prepared by over 100 specialists and researchers from throughout the world, Fascia: The Tensional Network of the Human Body will be ideal for all professionals who have an interest in fascia and human movement - physiotherapists, osteopathic physicians, osteopaths, chiropractors, structural integration practitioners, manual therapists, massage therapists, acupuncturists, yoga or Pilates instructors, exercise scientists and personal trainers - as well as physicians involved with musculoskeletal medicine, pain management and rehabilitation, and basic scientists working in the field. - Reflects the efforts of almost 100 scientists and clinicians from throughout the world - Offers comprehensive coverage ranging from anatomy and physiology, clinical conditions and associated therapies, to recently developed research techniques - Explores the role of fascia as a bodywide communication system - Presents the latest information available on myofascial force transmission which helps establish a scientific basis for given clinical experiences - Explores the importance of fascia as a sensory organ - for example, its important proprioceptive and nociceptive functions which have implications for the generation of low back pain - Describes new imaging methods which confirm the connectivity of organs and tissues - Designed to organize relevant information for professionals involved in the therapeutic manipulation of the body's connective tissue matrix (fascia) as well as for scientists involved in basic science research - Reflects the increasing need for information about the properties of fascia, particularly for osteopaths, massage therapists, physiotherapists and other complementary health care professionals - Offers new insights on the fascial related foundations of Traditional Chinese Medicine Meridians and the fascial effects of acupuncture
Author: Vishwanath Venketaraman
Publisher:
ISBN: 9783039435029
Category :
Languages : en
Pages : 120
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Book Description
TB is considered as one of the oldest documented infectious diseases in the world and is believed to be the leading cause of mortality due to a single infectious agent. Mtb, the causative agent responsible for TB, continues to afflict millions of people worldwide. Furthermore, one-third of the entire world's population has latent TB. Consequently, there has been a worldwide effort to eradicate and limit the spread of Mtb through the use of antibiotics. However, management of TB is becoming more challenging with the emergence of drug-resistant and multi-drug resistant strains of Mtb. Furthermore, when administered, many of the anti-TB drugs commonly present severe complications and side effects. Novel approaches to enhance the host immune responses to completely eradicate Mtb infection are urgently needed. This Special Issue will therefore cover most recent advances in the area of host-directed therapies for TB.
