scholarly journals Neutropenia and Large Granular Lymphocyte Leukemia: From Pathogenesis to Therapeutic Options

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2800
Author(s):  
Giulia Calabretto ◽  
Antonella Teramo ◽  
Gregorio Barilà ◽  
Cristina Vicenzetto ◽  
Vanessa Rebecca Gasparini ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia ◽  
Effective Therapeutic Strategy ◽  
Neutropenic Patients ◽  
Prospective Trials ◽  
Stat3 Mutations ◽  
Made In

Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated neutropenia represents the clinical hallmark of the disease, being present in up to 80% of cases. New advances were made in the biological characterization of neutropenia in these patients, in particular STAT3 mutations and a discrete immunophenotype are now recognized as relevant features. Nevertheless, the etiology of LGLL-related neutropenia is not completely elucidated and several mechanisms, including humoral abnormalities, bone marrow infiltration/substitution and cell-mediated cytotoxicity might cooperate to its pathogenesis. As a consequence of the multifactorial nature of LGLL-related neutropenia, a targeted therapeutic approach for neutropenic patients has not been developed yet; moreover, specific guidelines based on prospective trials are still lacking, thus making the treatment of this disorder a complex and challenging task. Immunosuppressive therapy represents the current, although poorly effective, therapeutic strategy. The recent identification of a STAT3-mediated miR-146b down-regulation in neutropenic T-LGLL patients emphasized the pathogenetic role of STAT3 activation in neutropenia development. Accordingly, JAK/STAT3 axis inhibition and miR-146b restoration might represent tempting strategies and should be prospectively evaluated for the treatment of neutropenic LGLL patients.

Mitochondrial dysfunction and the AKI-to-CKD transition

2020 ◽  
Vol 319 (6) ◽  
pp. F1105-F1116
Author(s):  
Mingzhu Jiang ◽  
Mi Bai ◽  
Juan Lei ◽  
Yifan Xie ◽  
Shuang Xu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Mitochondrial Homeostasis ◽  
Cycle Arrest ◽  
Persistent Inflammation ◽  
Acute Injuries ◽  
Nephron Loss ◽  
Effective Therapeutic Strategy

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.

scholarly journals Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia

Haematologica ◽  
2017 ◽  
Vol 103 (2) ◽  
pp. 304-312 ◽  
Author(s):  
Paula Savola ◽  
Oscar Brück ◽  
Thomas Olson ◽  
Tiina Kelkka ◽  
Markku J. Kauppi ◽  
...  
Keyword(s):  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia ◽  
Felty Syndrome ◽  
Common Pathogenesis ◽  
Stat3 Mutations

scholarly journals Clinical diagnostic and therapeutic guidelines of stroke neurorestoration (2020 China version)

2020 ◽  
Vol 8 (4) ◽  
pp. 241-251
Author(s):  
Xiaoling Guo ◽  
Qun Xue ◽  
Jianhua Zhao ◽  
Yi Yang ◽  
Yang Yu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
International Association ◽  
Stroke Patients ◽  
Clinical Diagnostic ◽  
Therapeutic Guidelines ◽  
Effective Therapeutic Strategy ◽  
Chinese Association ◽  
Therapeutic Recommendations ◽  
Made In

Stroke is the main cause of death and disability among Chinese, and neurorestoration is an effective therapeutic strategy for patients with stroke. In recent years, many achievements have been made in stroke neurorestoration, but viewpoints for managing stroke vary per discipline. In order to promote standardization of diagnosis and treatment for stroke neurorestoration, the Chinese Association of Neurorestoratology (CANR; Preparatory) and China Committee of International Association of Neurorestoratology (IANR-China Committee) organized professional experts in the field to integrate fragmented neurorestorative methods and establish clinical diagnostic and therapeutic guidelines for stroke neurorestoration. This guideline includes the diagnosis and staging of stroke and therapeutic recommendations for neurorestoration at different stages of stroke in order to improve survival and quality of life of stroke patients.

Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients

Leukemia ◽  
2019 ◽  
Vol 34 (4) ◽  
pp. 1116-1124 ◽  
Author(s):  
Gregorio Barilà ◽  
Antonella Teramo ◽  
Giulia Calabretto ◽  
Cristina Vicenzetto ◽  
Vanessa Rebecca Gasparini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Large Granular Lymphocyte ◽  
Single Center ◽  
Large Granular Lymphocyte Leukemia ◽  
Single Center Experience ◽  
Stat3 Mutations

scholarly journals Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 201
Author(s):  
Laura Cortese ◽  
Pete W. Christopherson ◽  
Alessandra Pelagalli
Keyword(s):  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Functional Characterization ◽  
Current Status ◽  
Significant Progress ◽  
Therapeutic Benefits ◽  
Platelet Structure ◽  
Made In

Significant progress has been made in the functional characterization of canine platelets in the last two decades. The role of canine platelets in hemostasis includes their adhesion to the subendothelium, activation, and aggregation, leading to primary clot formation at the site of injury. Studies on canine platelet function and advancements in laboratory testing have improved the diagnosis and understanding of platelet-related disorders as well as the knowledge of the mechanisms behind these diseases. This review focuses on the most recent discoveries in canine platelet structure, function, and disorders; and discusses the efficacy of various tests in the diagnosis of platelet-related disorders. With the relatively recent discovery of angiogenetic and reparative effects of growth factors found in platelets, this review also summarizes the use of canine platelet-rich plasma (PRP) alone or in association with stem cells in regenerative therapy. The characterization of proteomic and lipidomic profiles and development of platelet gene therapy in veterinary species are areas of future study with potential for major therapeutic benefits.

scholarly journals Large granular lymphocyte leukemia serum and corresponding hematological parameters reveal unique cytokine and sphingolipid biomarkers and associations with STAT3 mutations

2020 ◽  
Vol 9 (18) ◽  
pp. 6533-6549 ◽  
Author(s):  
Kristine C. Olson ◽  
Katharine B. Moosic ◽  
Marieke K. Jones ◽  
Paige M. K. Larkin ◽  
Thomas L. Olson ◽  
...  
Keyword(s):  
Hematological Parameters ◽  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia ◽  
Stat3 Mutations

Public Diplomacy in Confl ict Zones:Military Information Operations Meet Political Counter-Insurgency

2008 ◽  
Vol 3 (3) ◽  
pp. 277-297 ◽  
Author(s):  
Evan Potter ◽  
Daryl Copeland
Keyword(s):  
Soft Power ◽  
Public Diplomacy ◽  
First Century ◽  
Hard Power ◽  
Information Operations ◽  
Twenty First Century ◽  
Foreign Ministries ◽  
Made In

AbstractThe case made in this article is threefold: that the resolution of conflicts in the twenty-first century will depend much more on the judicious use of soft rather than hard power; that the type of soft power exercised through public diplomacy will move increasingly from monologue to dialogue and collaboration; and that there is an increasing convergence of thinking both in defence departments and foreign ministries on the role of public diplomacy in resolving conflict in asymmetrical warfare. That convergence is expressed in this article's characterization of the 'guerrilla diplomat'.

Characterization of a variant of PAC-1 in large granular lymphocyte leukemia

2003 ◽  
Vol 32 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Ravi Kothapalli ◽  
Sean J Yoder ◽  
Irina Kusmartseva ◽  
Thomas P Loughran
Keyword(s):  
Large Granular Lymphocyte ◽  
Large Granular Lymphocyte Leukemia

scholarly journals Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Li Sui ◽  
Rui-Hong Zhang ◽  
Ping Zhang ◽  
Ke-Li Yun ◽  
Hong-Cai Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Side Effects ◽  
Therapeutic Strategy ◽  
Lead Toxicity ◽  
Protective Role ◽  
Molecular Processes ◽  
Effective Therapeutic Strategy ◽  
Mtorc1 Pathway ◽  
Set Up

Lead is a metal with many recognized adverse health side effects, and yet the molecular processes in cardiofibroblasts underlying lead toxicity are still poorly understood. Our current findings will help to understand the role of lead-mediated toxicity in cardiofibroblasts, indicating that autophagy serves a protective role in response to ER stress, which affords to set up an effective therapeutic strategy for the numerous diseases related to lead-toxicity.

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