scholarly journals Pharmacological Modulation of Toll-Like Receptors in Brain Disorders

2021 ◽  
Author(s):  
Tahani K. Alshammari ◽  
Nouf M. Alrasheed ◽  
Lina Alhushan ◽  
Reema Alhoutah ◽  
Anfal F. Bin Dayel ◽  
...  
Keyword(s):  
Common Factor ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Resistance Mechanisms ◽  
Preclinical Studies ◽  
Brain Disorders ◽  
Toll Like Receptors ◽  
Knowledge Gaps ◽  
Considerable Evidence ◽  
New Treatment

The knowledge regarding pathological and treatment resistance mechanisms involved in the pathology of complex brain disorders is far from understood. The neuroinflammation hypothesis of psychiatric, neurological, and neurodegenerative diseases is well-acknowledged. However, this hypothesis is far from understood. Toll-like receptors (TLRs) family is an innate immunity molecule implicated in neuroinflammation in complex brain disorders. This chapter reviews considerable evidence indicating that activation of endotoxins such as lipopolysaccharide is a common factor. Additionally, we report clinical and preclinical studies highlighting the link between lipopolysaccharide, TLRs, and different types of brain disorders. Also, we review the current pharmacological modulations of TLRs. Hoping we would help in filling our knowledge gaps and highlight potential links to tackle new angles in managing complex brain disorders. This chapter’s primary goal is to encourage scientists and researchers to conduct future studies characterizing the nature of endotoxin activation of TLRs in complex brain disorders, filling our knowledge gaps, and finding new treatment strategies.

scholarly journals External Basic Hyperthermia Devices for Preclinical Studies in Small Animals

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4628 ◽  
Author(s):  
Marjolein I. Priester ◽  
Sergio Curto ◽  
Gerard C. van Rhoon ◽  
Timo L. M. ten Hagen
Keyword(s):  
Solid Tumor ◽  
Low Cost ◽  
Treatment Strategies ◽  
Small Animals ◽  
Preclinical Studies ◽  
Research Groups ◽  
Tumor Treatment ◽  
Preclinical Testing ◽  
Mild Hyperthermia ◽  
New Treatment

Preclinical studies have shown that application of mild hyperthermia (40–43 °C) is a promising adjuvant to solid tumor treatment. To improve preclinical testing, enhance reproducibility, and allow comparison of the obtained results, it is crucial to have standardization of the available methods. Reproducibility of methods in and between research groups on the same techniques is crucial to have a better prediction of the clinical outcome and to improve new treatment strategies (for instance with heat-sensitive nanoparticles). Here we provide a preclinically oriented review on the use and applicability of basic hyperthermia systems available for solid tumor thermal treatment in small animals. The complexity of these techniques ranges from a simple, low-cost water bath approach, irradiation with light or lasers, to advanced ultrasound and capacitive heating devices.

Development of Peptides that Inhibit Aminoglycoside-Modifying Enzymes and β-Lactamases for Control of Resistant Bacteria

2020 ◽  
Vol 21 (10) ◽  
pp. 1011-1026
Author(s):  
Bruna O. Costa ◽  
Marlon H. Cardoso ◽  
Octávio L. Franco
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Specific Chemical ◽  
Target Interaction ◽  
Multiresistant Bacteria ◽  
Acute Bacterial Infections

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.

Humoral Immunity in Heart Failure

2019 ◽  
Vol 19 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Amrita Sarkar ◽  
Khadija Rafiq
Keyword(s):  
Heart Failure ◽  
Humoral Immunity ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism ◽  
Peripheral Vascular ◽  
Cardiac Inflammation ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
New Treatment ◽  
Immunity Function

Cardiovascular Disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to Heart Failure (HF). There are several treatments available all over the world, but still, CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is a major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play a specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential and may suggest potential new treatment strategies.

scholarly journals Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Tumor Metabolism ◽  
Resistance Mechanisms ◽  
Metabolic Reprogramming ◽  
Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

scholarly journals Cancer Vaccines for Genitourinary Tumors: Recent Progresses and Future Possibilities

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 623
Author(s):  
Brigida Anna Maiorano ◽  
Giovanni Schinzari ◽  
Davide Ciardiello ◽  
Maria Grazia Rodriquenz ◽  
Antonio Cisternino ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Viral Vectors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Tumor Development ◽  
Resistance Mechanisms ◽  
High Morbidity ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
New Treatment

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neoplasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched PubMed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further preclinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

scholarly journals Melanoma Single-Cell Biology in Experimental and Clinical Settings

2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Hans Binder ◽  
Maria Schmidt ◽  
Henry Loeffler-Wirth ◽  
Lena Suenke Mortensen ◽  
Manfred Kunz
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Intracellular Signaling ◽  
Cell Biology ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
Treatment Resistance ◽  
Resistance Mechanisms ◽  
Cellular Heterogeneity

Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8+ T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.

scholarly journals Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 265
Author(s):  
Maria-Luisa Pérez-Lozano ◽  
Annabelle Cesaro ◽  
Marija Mazor ◽  
Eric Esteve ◽  
Sabine Berteina-Raboin ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Natural Product ◽  
Treatment Strategies ◽  
Cartilage Degradation ◽  
Therapeutic Strategies ◽  
Clinical Models ◽  
Osteoarthritic Joint ◽  
Dietary Components ◽  
New Treatment ◽  
Review Current

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment. In the present review, we provide an overview of current and emerging natural-product-based research treatments for OA management by drawing attention to experimental, pre-clinical, and clinical models. Herein, we review current and emerging natural-product-based research treatments for OA management.

scholarly journals Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 607
Author(s):  
Alice Indini ◽  
Francesco Grossi ◽  
Mario Mandalà ◽  
Daniela Taverna ◽  
Valentina Audrito
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Biological Behavior ◽  
Therapeutic Implications ◽  
Systemic Treatments

Malignant melanoma represents the most fatal skin cancer due to its aggressive biological behavior and high metastatic potential. Treatment strategies for advanced disease have dramatically changed over the last years due to the introduction of BRAF/MEK inhibitors and immunotherapy. However, many patients either display primary (i.e., innate) or eventually develop secondary (i.e., acquired) resistance to systemic treatments. Treatment resistance depends on multiple mechanisms driven by a set of rewiring processes, which involve cancer metabolism, epigenetic, gene expression, and interactions within the tumor microenvironment. Prognostic and predictive biomarkers are needed to guide patients’ selection and treatment decisions. Indeed, there are no recognized clinical or biological characteristics that identify which patients will benefit more from available treatments, but several biomarkers have been studied with promising preliminary results. In this review, we will summarize novel tumor metabolic pathways and tumor-host metabolic crosstalk mechanisms leading to melanoma progression and drug resistance, with an overview on their translational potential as novel therapeutic targets.

scholarly journals The Optimal First-Line Therapy ofHelicobacter pyloriInfection in Year 2012

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chao-Hung Kuo ◽  
Fu-Chen Kuo ◽  
Huang-Ming Hu ◽  
Chung-Jung Liu ◽  
Sophie S. W. Wang ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Treatment Strategies ◽  
Sequential Therapy ◽  
Antibiotics Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Metronidazole Resistance ◽  
Rescue Treatment ◽  
New Treatment ◽  
H Pylori

This paper reviews the literature about first-line therapies forH. pyloriinfection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.

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