scholarly journals Harnessing CD8+CD28− Regulatory T Cells as a Tool to Treat Autoimmune Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2973
Author(s):  
Sabrina Ceeraz ◽  
Charlotte R. Thompson ◽  
Richard Beatson ◽  
Ernest H. Choy
Keyword(s):  
Cell Therapy ◽  
Therapeutic Strategy ◽  
Surface Expression ◽  
Current Treatment ◽  
Review Article ◽  
Healthy Individuals ◽  
T Regulatory Cell ◽  
Preclinical Models ◽  
Inflammatory Conditions ◽  
Treg Population

T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the CD4+ Treg population has been extensively characterized, as a result of defined phenotypic and functional readouts. In this review article, we discuss the development and biology of CD8+ Tregs and their role in murine and human disease indications. A subset of CD8+ Tregs that lack the surface expression of CD28 (CD8+CD28− Treg) has proved efficacious in preclinical models. CD8+CD28− Tregs are present in healthy individuals, but their impaired functionality in disease renders them less effective in mediating immunosuppression. We primarily focus on harnessing CD8+ Treg cell therapy in the clinic to support current treatment for patients with autoimmune or inflammatory conditions.

scholarly journals De-Coding the Contributions of the Viral RNAs to Alphaviral Pathogenesis

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 771
Author(s):  
Autumn T. LaPointe ◽  
Kevin J. Sokoloski
Keyword(s):  
Host Response ◽  
Severe Disease ◽  
Review Article ◽  
Structural Proteins ◽  
Virulence Determinants ◽  
Healthy Individuals ◽  
Viral Rnas ◽  
Positive Sense ◽  
Identification And Characterization

Alphaviruses are positive-sense RNA arboviruses that are capable of causing severe disease in otherwise healthy individuals. There are many aspects of viral infection that determine pathogenesis and major efforts regarding the identification and characterization of virulence determinants have largely focused on the roles of the nonstructural and structural proteins. Nonetheless, the viral RNAs of the alphaviruses themselves play important roles in regard to virulence and pathogenesis. In particular, many sequences and secondary structures within the viral RNAs play an important part in the development of disease and may be considered important determinants of virulence. In this review article, we summarize the known RNA-based virulence traits and host:RNA interactions that influence alphaviral pathogenesis for each of the viral RNA species produced during infection. Overall, the viral RNAs produced during infection are important contributors to alphaviral pathogenesis and more research is needed to fully understand how each RNA species impacts the host response to infection as well as the development of disease.

scholarly journals Effect of rapamycin on mitochondria and lysosomes in fibroblasts from patients with mtDNA mutations

2021 ◽  
Author(s):  
Nashwa J. Cheema ◽  
Jessie M. Cameron ◽  
David A. Hood
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Current Treatment ◽  
Basal Respiration ◽  
Healthy Individuals ◽  
Cellular Mechanisms ◽  
Mtdna Mutations ◽  
Cultured Skin ◽  
Patient Cell

Maintaining mitochondrial function and dynamics is crucial for cellular health. In muscle, defects in mitochondria result in severe myopathies where accumulation of damaged mitochondria causes deterioration and dysfunction. Importantly, understanding the role of mitochondria in disease is a necessity to determine future therapeutics. One of the most common myopathies is mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), which has no current treatment. Recently, MELAS patients treated with rapamycin exhibited improved clinical outcomes. However, the cellular mechanisms of rapamycin effects in MELAS patients are currently unknown. In this study, we used cultured skin fibroblasts as a window into the mitochondrial dysfunction evident in MELAS cells, as well as to study the mechanisms of rapamycin action, compared to control, healthy individuals. We observed that mitochondria from patients were fragmented, had a 3-fold decline in the average speed of motility, a 2-fold reduced mitochondrial membrane potential and a 1.5-2-fold decline in basal respiration. Despite the reduction in mitochondrial function, mitochondrial import protein Tim23 was elevated in patient cell lines. MELAS fibroblasts exhibited increased MnSOD levels and lysosomal function when compared to healthy controls. Treatment of MELAS fibroblasts with rapamycin for 24 hrs resulted in increased mitochondrial respiration compared to control cells, a higher lysosome content, and a greater localization of mitochondria to lysosomes. Our studies suggest that rapamycin has the potential to improve cellular health even in the presence of mtDNA defects, primarily via an increase in lysosomal content.

scholarly journals Current treatment of post-tonsillectomy pain: a review

2021 ◽  
Vol 7 (10) ◽  
pp. 1708
Author(s):  
Santosh Kumar Swain
Keyword(s):  
Pediatric Patients ◽  
Hospital Staff ◽  
Current Treatment ◽  
Review Article ◽  
Age Group ◽  
Throat Pain ◽  
Pediatric Age Group ◽  
Post Operative Pain ◽  
Active Research ◽  
Pain Analgesics

<p class="abstract">Tonsillectomy is one of the most common surgical procedures performed by an otorhinolaryngologist. This surgery is done more in the pediatric age group. Although tonsillectomy is safe and effective surgery, it is usually associated with significant post-operative pain. Analgesics used for post-tonsillectomy pain is often inadequate. Severe throat pain following tonsillectomy has been documented for decades. Patients or parents/caretakers often worry about such severe pain in the home. The pain following tonsillectomy is usually intense and long-lasting. The severe post-tonsillectomy pain often overstrains the patient, family, and hospital staff. Regular changes in the analgesic armamentarium, particularly in pediatric patients are making the treatment of post-tonsillectomy pain more challenging. Pain following the tonsillectomy period continues to be a highly debated issue and an area of active research. Throat pain in the post-tonsillectomy period can result in significant morbidity among patients. There are different analgesics available; each one has its risk profile and side effects when used for controlling post-tonsillectomy pain. This review article discusses on recent management of post-tonsillectomy pain. This article reviews the epidemiology, pathophysiology, impact of post-tonsillectomy pain, and details of medications used for controlling post-tonsillectomy pain.</p>

scholarly journals Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases

2016 ◽  
Vol 45 (2) ◽  
pp. 205-221 ◽  
Author(s):  
C. Grégoire ◽  
C. Lechanteur ◽  
A. Briquet ◽  
É. Baudoux ◽  
F. Baron ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Inflammatory Bowel Diseases ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Review Article ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Inhibition of the Formation In Vitro of Putatively Carcinogenic Metabolites Derived from S. haematobium and O. viverrini by Combination of Drugs with Antioxidants

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3842
Author(s):  
Maria João Gouveia ◽  
Verónica Nogueira ◽  
Bruno Araújo ◽  
Fátima Gärtner ◽  
Nuno Vale
Keyword(s):  
Dna Adducts ◽  
Therapeutic Strategy ◽  
Drug Repurposing ◽  
Inhibitory Effect ◽  
Current Treatment ◽  
Combination Drugs ◽  
Therapeutic Alternatives ◽  
And Control ◽  
Novel Therapeutic

Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.

scholarly journals Scalp Pruritus: Review of the Pathogenesis, Diagnosis, and Management

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Ploysyne Rattanakaemakorn ◽  
Poonkiat Suchonwanit
Keyword(s):  
Therapeutic Strategy ◽  
Skin Diseases ◽  
Underlying Disease ◽  
Review Article ◽  
Skin Changes ◽  
Underlying Condition ◽  
Appropriate Treatment ◽  
Underlying Diseases ◽  
Frequent Problem

Scalp pruritus is a frequent problem encountered in dermatological practice. This disorder is caused by various underlying diseases and is a diagnostic and therapeutic challenge. Scalp pruritus may be localized to the scalp or extended to other body areas. It is sometimes not only associated with skin diseases or specific skin changes, but also associated with lesions secondary to rubbing or scratching. Moreover, scalp pruritus may be difficult to diagnose and manage and may have a great impact on the quality of life of patients. It can be classified as dermatologic, neuropathic, systemic, and psychogenic scalp pruritus based on the potential underlying disease. A thorough evaluation of patients presenting with scalp pruritus is important. Taking history and performing physical examination and further investigations are essential for diagnosis. Therapeutic strategy comprises removal of the aggravating factors and appropriate treatment of the underlying condition. All treatments should be performed considering an individual approach. This review article focuses on the understanding of the pathophysiology and the diagnostic and therapeutic management of scalp pruritus.

Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14

2001 ◽  
Vol 280 (1) ◽  
pp. L58-L68 ◽  
Author(s):  
Ulrich Maus ◽  
Susanne Herold ◽  
Heidrun Muth ◽  
Regina Maus ◽  
Leander Ermert ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Blood Monocytes ◽  
Blood Leukocytes ◽  
Alveolar Air ◽  
Inflammatory Conditions ◽  
Air Space ◽  
Factor Α ◽  
Necrosis Factor

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-α message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are “primed” for enhanced responsiveness to endotoxin with increased cytokine expression.

scholarly journals Identification of an Immunomodulating Agent from Mycobacterium leprae

2005 ◽  
Vol 73 (5) ◽  
pp. 2744-2750 ◽  
Author(s):  
Yumi Maeda ◽  
Tetsu Mukai ◽  
John Spencer ◽  
Masahiko Makino
Keyword(s):  
Mycobacterium Leprae ◽  
Surface Expression ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Healthy Individuals ◽  
Reactive Protein ◽  
Histocompatibility Complex ◽  
Toll Like Receptor 2 ◽  
Antigen Presenting ◽  
Dc Maturation

ABSTRACT A search for an immunomodulating agent from mycobacteria was carried out using Mycobacterium leprae. The antigenicity of each fraction of the bacterial membrane, which contains the most antigenic components of M. leprae, was assessed by using sera from paucibacillary leprosy. N-terminal sequencing of the serum-reactive protein and functional assessment of the membrane fractions using monocyte-derived dendritic cells (DCs) identified major membrane protein II (MMP-II) as one of the efficient T-cell-activating candidates. Purified MMP-II stimulated DCs from healthy individuals to produce interleukin-12 p70 and up-regulated the surface expression of major histocompatibility complex class I and II, CD86, and CD83 molecules. Also, there was an increase in the percentage of CD83+ cells in the DC population. Furthermore, MMP-II-pulsed DCs expressed their derivatives on their surfaces. Using Toll-like receptor 2 (TLR-2)-dependent receptor constructs, we found that TLR-2 signaling was involved in DC maturation induced by MMP-II. Taken together, MMP-II can be recognized as an immunomodulating protein in terms of activation of antigen-presenting cells and innate immunity.

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