Platelet Cytokines and Vascular Diseases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-36-SCI-36
Author(s):  
Christian Weber
Keyword(s):  
Immune Cells ◽  
Vascular Inflammation ◽  
Neointimal Hyperplasia ◽  
Vascular Diseases ◽  
Special Focus ◽  
Advisory Committees ◽  
The Past ◽  
Cytokines And Chemokines ◽  
Equity Ownership ◽  
Prevention Of Cardiovascular Disease

Abstract Abstract SCI-36 During the past decade it has become increasingly clear that platelets exert important functions in the context of inflammation, beyond their role in hemostasis. Platelets may adhere to intact endothelial cells and promote local vascular inflammation by recruiting leukocytes via direct interactions or by secreting inflammatory mediators such as cytokines and chemokines. Accordingly, platelet-derived chemokines play a crucial role in directing leukocytes to sites of vascular injury or dysfunction, thereby contributing to neointimal hyperplasia or atherosclerosis. In addition, platelet-derived cytokines can shape the local inflammatory environment. In this overview, I will discuss the function of platelets as immune cells that potentiate vascular inflammation with a special focus on platelet-derived chemokines: their effects and interactions and their potential quality as targets for the treatment and/or prevention of cardiovascular disease. Disclosures: Weber: Carolus Therapeutics: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees.

MAPK p38/Ulk1 pathway inhibits autophagy and induces IL-1β expression in hepatic stellate cells

2022 ◽  
Author(s):  
Li Jin ◽  
Juan Li ◽  
ShuJuan Yang ◽  
Rou Zhang ◽  
Chunhua Hu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Hepatic Inflammation ◽  
The Past ◽  
Cytokine Induction ◽  
Cytokines And Chemokines ◽  
The Relationship ◽  
Autophagy Inhibition ◽  
Lps Treatment

Background: In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells. It is unclear whether autophagy is involved in inflammatory cytokine induction in HSCs. Methods: MAPK p38, Ulk1 phosphorylation and the Ulk1-Atg13 complex were analyzed in HSC-T6 cells after LPS treatment. The relationship between autophagy inhibition and inflammation was investigated in primary rat HSCs. Results: We discovered that LPS inhibited autophagy through MAPK p38. The activation of MAPK p38 induced Ulk1 phosphorylation, which disrupted the Ulk1-Atg13 complex and therefore inhibited autophagy. Furthermore, in primary rat HSCs, we demonstrated that autophagy inhibition regulated IL-1β induction, which depended on the MAPK p38/Ulk1 pathway. Conclusions: Our results reveal a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1/Atg13 disruption, which inhibits autophagy and induces IL-1β expression in HSCs.

Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective. A Report From the International PNH Registry.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1525-1525 ◽  
Author(s):  
Petra Muus ◽  
Jeffrey Szer ◽  
Hubert Schrezenmeier ◽  
Robert A Brodsky ◽  
Monica Bessler ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Chest Pain ◽  
Board Of Directors ◽  
Disease Burden ◽  
Advisory Committees ◽  
Clone Size ◽  
The Past ◽  
Patient Reported ◽  
History Of ◽  
Equity Ownership

Abstract Abstract 1525 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis, a variable degree of bone marrow failure and thrombophilia, which may lead to reduced quality of life (QOL). There have been few reports of the disease burden of PNH from the patient's perspective. Aims: To describe patient-reported QOL, hospitalization, and missed work at time of PNH registry enrollment and to evaluate the association of these patient-reported outcomes (PROs) with demographics; patient reported symptoms (abdominal pain, chest pain and hemoglobinuria); and clinical characteristics (years since diagnosis, granulocyte clone size, underlying bone marrow disorder [BMD] and prior thrombotic event [TE]). Methods: Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry if they have a PNH clone regardless of clone size, other BMD, symptoms, or treatments. As part of the study, patients are asked to complete questionnaires at enrollment including the six subscales of the EORTC QLQ-C30 (range=0-100, higher scores better) and the FACIT-Fatigue scale (range=0-52, higher scores better). Patients are also asked “in the past 6 months have you been admitted to a hospital for your PNH” and “in the past 6 months did you miss work as a result of PNH” (questions about work were added later in the study). Statistical analysis used ANOVA and Chi-square tests as appropriate. Results: As of August 2010 there were 657 patients enrolled in the Registry. Of these, 377 (57%) patients completed a baseline questionnaire (BQ) and are included in this analysis. Patients with and without a completed BQ were comparable on most study variables, although patients with a higher clone size were less likely to complete a BQ. Patients had a mean age of 45.8±17.6 years; 54% were female. Median PNH (granulocyte) clone size was 75% (nearly two-thirds had a clone size ≥50%), 45% had BMD (mostly aplastic anemia) and 12% had history of TE. Abdominal pain in the last 6 months was reported by 45% of patients, chest pain by 28%, and hemoglobinuria by 64%. Mean EORTC scores (general population reference in parenthesis) were: global health=64.4 (71.2), physical functioning=79.7 (89.8), role functioning=73.9 (84.7), emotional functioning=76.0 (76.3), cognitive functioning=81.1 (86.1), and social functioning=77.2 (87.5). Thus, scores for PNH patients were decreased by about 10% in 4 of the 6 subscales. PNH patients had a mean FACIT-Fatigue score of 36.6, while a general population reference is 43.6 (or a 16% reduction). PROs were independent of time since diagnosis, PNH clone size, or underlying BMD. Males reported better physical, emotional, and social functioning and less fatigue than females (all p<.05). As expected, age strongly affected physical functioning (p<.01). Patients with prior TE reported worse global health, physical, role, cognitive functioning, and more fatigue than patients without prior TE (all p<.05). Patients reporting abdominal pain, chest pain, or hemoglobinuria had significantly worse EORTC and FACIT-fatigue scores on every scale (all p<.05). Overall, 26% of patients had a PNH-related hospitalization in the past 6 months. Patients who reported TE, abdominal pain, chest pain, or hemoglobinuria were more likely to be admitted to the hospital (all p<.05). There were 109 patients out of 244 (45%) who worked at a paid job. Of these,30% missed work in the past 6 months due to PNH. Patients were more likely to miss work if they had abdominal pain (47% vs 19%, p<.01 or hemoglobinuria (42% vs. 7%, p<.01). Conclusion: The disease burden to PNH patients is evident. Mean QOL is reduced in patients with PNH by 10 to 16% on most scales compared to the general population. One of four patients was hospitalized and 30% of patients with a paid job missed work due to PNH over a 6-month period. History of thrombosis and presence of PNH-related symptoms strongly affected QOL and hospitalization, while missed work was mostly impacted by symptoms. This global PNH Registry, which remains open to accrual ([email protected]), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment, including outcomes measured from the patient's perspective. Disclosures: Muus: Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. Bessler:Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy. Socié:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Urbano-Ispizua:Alexion: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Rosse:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kanakura:Alexion: Membership on an entity's Board of Directors or advisory committees. Khursigara:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell:Alexion Pharma International: Employment, Equity Ownership. Bedrosian:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Early Changes in Cytokines, Chemokines and Indices of Bone Metabolism in a Phase 2 Study of the Bruton Tyrosine Kinase (Btk) Inhibitor, Ibrutinib (PCI-32765) in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4039-4039 ◽  
Author(s):  
Ravi Vij ◽  
Betty Y. Chang ◽  
Jesus G. Berdeja ◽  
Carol Ann Huff ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Board Of Directors ◽  
Plasma Cells ◽  
Blood Levels ◽  
Employment Equity ◽  
Advisory Committees ◽  
Cytokines And Chemokines ◽  
Btk Inhibitor ◽  
Equity Ownership

Abstract Abstract 4039 Introduction: Bruton tyrosine kinase (Btk) is essential in the development and function of B cells through normal B cell receptor signaling, and it is down-regulated in non-malignant plasma cells. This is not the case in malignant plasma cells of patients with MM where robust Btk gene expression is usual. In addition, Btk is expressed and functional in osteoclasts and their precursors, which play a pathogenic role in MM-related bone disease, as well as growth and survival of MM in the microenvironment. Researchers in our group (Tai, Chang et al, Blood, 2012) recently demonstrated that the Btk inhibitor ibrutinib (PCI-32765) inhibited the interaction of MM cells with stromal cells, and inhibited the growth in vitro of MM colony forming cells from patient explants. Ibrutinib suppressed in vitro osteoclast differentiation and production of multiple cytokines and chemokines including CCL3, CCL4, IL-8, and TGF-β. Ibrutinib furthermore decreased MM progression and accompanying bone destruction in an in vivo SCID-Hu myeloma model. Based on these observations, we initiated a clinical trial of ibrutinib in patients with relapsed (R) and relapsed/refractory (R/R) MM. This report of early marker changes is based upon 7 patients who have completed 3 cycles of treatment. Methods: Patients with progressive disease (PD) after at least 2 prior lines of therapy received a fixed dose of oral ibrutinib 420 mg orally once daily, with a cycle defined as 28 days. Dexamethasone 40 mg weekly could be added if no response or PD was observed by cycle 2. Blood levels of cytokines, chemokines and bone markers (bone-specific alkaline phosphatase (bAP), sclerostin and RANKL) were assessed centrally at Days 1, 2, 8, and 15 of Cycle 1, Cycle 2 Day 1 and every 2 cycles thereafter, by single or multiplexed immunoassays. Serum cross-linked C-terminal peptide of collagen I (sCTx) was determined by a central lab at the start of Cycles 1 and 2 and every other cycle thereafter. Responses were assessed following the International Myeloma Working Group criteria (modified to include minimal response). Results: Thirteen patients [M/F: 8/5; median age 62, range 49–74 years] were enrolled between March 21 and June 6, 2012. All patients had received prior treatment with lenalidomide, bortezomib, alkylators and dexamethasone. 7 were refractory to their last treatment. At the time of data cut off, 7 of the 13 patients enrolled had completed 3 cycles of therapy and were the ones used for analysis. Over the course of three cycles, several markers relevant to bone metabolism exhibited gradual decreases. At Cy4D1 plasma RANKL, sclerostin, and bAP exhibited (median) decreases of 47%, 39%, and 36%, respectively. Relative changes in sCTx were more variable at Cy2D1, but there appeared to be a trend towards subject-by-subject decreases at C4D1 (Fig. 1). Factors promoting growth and angiogenesis (e.g. VEGF, EGF, and FGF) and cytokines and chemokines (CCL3, CCL4, TNFα, Groα and MDC) with roles in MM micro-environmental interactions exhibited similar reductions (Fig. 2). Among these the most dramatic and consistent changes were in CCL3 and CCL4, chemokines enhancing adhesive interactions contributing to osteolysis in MM, which showed median decreases of 43% and 77% at Cy4D1, respectively. Ibrutinib has been uniformly well tolerated and the safety experience to date has been similar to that noted in other studies of ibrutinib in lymphoma and CLL. Conclusions: Early reductions in blood levels of cytokines, chemokines, markers of bone metabolism, and pro-angiogenic and growth factors, were observed among MM patients treated with ibrutinib, which were consistent with pre-clinical studies. Among markers related to bone metabolism, it appeared that changes in regulatory molecules (sclerostin, RANKL) were more marked and perhaps preceded changes in markers of osteoclast (sCTx) or osteoblast (bAP) activity. Elucidation of these patterns and their significance will require longer follow-up of a larger number of patients. These results indicate that ibrutinib can exert significant biologic effects on the microenvironment in MM. Clinical correlations will be forthcoming based upon maturing results over the next several months. Disclosures: Vij: Millennium: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Onyx: Honoraria, Research Funding. Chang:Pharmacyclics, Inc.: Employment, Equity Ownership. Huff:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Chang:Pharmacyclics, Inc.: Employment, Equity Ownership. Moussa:Pharmacyclics, Inc.: Employment, Equity Ownership. Buggy:Pharmacyclics: Employment, Equity Ownership. Elias:Pharmacyclics, Inc.: Employment, Equity Ownership. Richardson:Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

Mutations Modifying Risk in NPM1+ AML

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2592-2592
Author(s):  
Jessica Leonard ◽  
Jennifer Dunlap ◽  
Tanaya L Neff ◽  
Andrea Warrick ◽  
Fei Yang ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Analysis ◽  
Advisory Committees ◽  
Relapse Risk ◽  
The Past ◽  
Oregon Health ◽  
Equity Ownership ◽  
Risk Of Relapse

Abstract Introduction: Favorable risk acute myeloid leukemia (AML) is defined by recurrent genetic abnormalities including core binding factor rearrangements such as inv(16) and t(8,21), normal cytogenetics with isolated mutations of NPM1, or bi-allelic mutations of CEBPA. Approximately 60% of patients are cured with standard 7+3 induction and cytarabine consolidation, which is comparable to survival rates of patients who receive allogeneic stem cell transplant (SCT). However, 20-30% of patients treated with chemotherapy still relapse, and relapsed disease remains the leading cause of death in this group. Even if relapsed patients achieve CR2 with salvage chemotherapy, their survival with allogeneic SCT is reduced compared to patients transplanted in CR1. Thus, predicting which favorable risk AML patients are more likely to relapse after chemotherapy would help guide therapy and improve patient outcomes. Recent publications have proposed that additional mutations in genes such as IDH1, IDH2, or DMT3A may impact relapse risk, but reports are conflicting. In addition, studies using minimal residual disease to evaluate disease burden after induction and consolidation has also been shown to predict relapse. We have used high throughput next generation sequencing (NGS) as diagnostic panel for AML at our institution for the past 2 years. This panel looks for mutations in 42 different genes known to be associated with acute leukemias and can quantitatively evaluate genetic MRD at a sensitivity of about 0.1%. We are analyzing favorable risk AML patients in an effort to identify additional mutations that predict relapse and in the process of evaluating the ability of this panel to evaluate MRD. Methods: Clinical samples were obtained with informed consent and with the approval of our institutional IRB. A targeted NGS panel was designed using multiplexed Ion AmpliSeq Designer (Life Technologies) software to amplify and sequence 42 genes relevant to hematopoietic malignancies. 20ng of DNA from bone marrow or blood was used to generate amplicon-based libraries that were sequenced using an Ion Torrent PGM. Bioinformatics analysis was performed using the Torrent Suite v.3.2 pipeline. Open source programs and lab-developed algorithms were used for variant annotation and mutation prediction.Patients with favorable risk AML diagnosed within the past two years had sequencing data available in their medical records. For patients diagnosed >2 years ago, archival samples were obtained and DNA extracted from isolated mononuclear cells or formalin-fixed paraffin-embedded tissue according to standard protocols. Results: We identified 57 patients with favorable risk AML diagnosed at OHSU over the past five years. 48 had enough biopsy material for genetic analysis. Of the 48, 17% had t (8;21), 29% had inv(16), 46% were NPM1+, and 8% had CEBPA mutations. Seven patients received transplant in CR1 for either residual disease or physician discretion. Of the remaining 41 patients, 11 patients relapsed (26%) and 8 of the 11 were NPM1+. Of the 8 relapsed NPM1+ patients, all had additional DNMT3A R882 mutations, IDH1/2 mutations, or both. 13 NPM1+ non-relapsed patients have been evaluated by sequencing to date and only 5 of 13 in the non-relapsed group had additional mutations in DNMT3A and/or IDH1/2(P=0.0185), however only 2 of the 5 had the R882 DNMT3A mutation. No DNMT3A, IDH1 or IDH2 mutations were identified in patients with t(8;21), inv (16) or biallelic CEBPA AML. Conclusions: Although our numbers are small, the presence of the R882 DNMT3A mutation appears to increase the risk of relapse in NPM1+ patients (Figure 1). Other DNMT3A point mutations do not seem to impact the risk of relapse and should be considered separately for relapse risk. Complete analysis and evaluation of MRD is underway. Figure 1. Figure 1. Disclosures Dunlap: Oregon Health & Sciences University: Employment. Druker:Bristol-Myers Squibb: Research Funding; McGraw Hill: Patents & Royalties; Oncotide Pharmaceuticals: Research Funding; Millipore: Patents & Royalties; Leukemia & Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptose Therapeutics Inc.: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; AstraZeneca: Consultancy; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; CTI Biosciences, Inc.: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Cylene Pharmaceuticals: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Fred Hutchinson Cancer Research Center: Research Funding; Henry Stewart Talks: Patents & Royalties; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharamceuticals: Research Funding; Molecular MD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Oregon Health and Science University: Patents & Royalties; Roche TCRC, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sage Bionetworks: Research Funding.

scholarly journals The role of immune cells in the development of adipose tissue dysfunction in cardiovascular diseases

2019 ◽  
pp. 92-98 ◽  
Author(s):  
E. G. Uchasova ◽  
O. V. Gruzdeva ◽  
Yu. A. Dyleva ◽  
E. V. Belik ◽  
O. L. Barbarash
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Vascular Diseases ◽  
Inflammatory Cells ◽  
Metabolic Dysfunction ◽  
Perivascular Adipose Tissue ◽  
Cytokines And Chemokines ◽  
Adipose Tissue Dysfunction ◽  
Physiological Properties ◽  
Cellular Signal

Adipose tissue dysfunction characterized by a loss of homeostatic functions It is observed in patients with obesity, insulin resistance and diabetes. In case of violation of the physiological properties in adipose tissue, an increased production of cytokines and chemokines occurs with the infiltration of tissue by immune cells. In turn, immune cells also produce cytokines, metalloproteinases, reactive oxygen species and chemokines, which are involved in tissue remodeling, cellular signal transduction and immunity regulation. The presence of inflammatory cells in adipose tissue affects organs and tissues. So in the blood vessels, inflammation of perivascular adipose tissue leads to vascular remodeling, superoxide production, endothelial dysfunction with loss of the bioavailability of nitric oxide, contributing to the development of various vascular diseases. In adipose tissue dysfunction, adipokines are also produced, such as leptin, resistin, and visfatin. These substances contribute to metabolic dysfunction, alter systemic homeostasis, sympathetic outflow, glucose regulation, and insulin sensitivity. Thus, the study of the mechanisms of interaction between immune cells and adipose tissue is promising and may be an important therapeutic target.

Platelets: Angels and demons dancing on the immune stage. Nutrition conducts the orchestra

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
Platelet Function ◽  
Immune Cells ◽  
Dual Role ◽  
Immune Functions ◽  
Omega 3 ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Inflammatory Processes

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

scholarly journals Addressing the changing rehabilitation needs of patients undergoing thoracic surgery

2021 ◽  
Vol 18 ◽  
pp. 147997312199478
Author(s):  
Daniel Langer
Keyword(s):  
Thoracic Surgery ◽  
Functional Limitations ◽  
Pulmonary Complications ◽  
Current Evidence ◽  
Outpatient Rehabilitation ◽  
Special Focus ◽  
Rehabilitative Treatment ◽  
The Past ◽  
Hospitalization Period ◽  
Rehabilitation Needs

The rehabilitation needs of individuals undergoing thoracic surgery are changing, especially as surgical management is increasingly being offered to patients who are at risk of developing functional limitations during and after hospital discharge. In the past rehabilitative management of these patients was frequently limited to specific respiratory physiotherapy interventions in the immediate postoperative setting with the aim to prevent postoperative pulmonary complications. In the past two decades, this focus has shifted toward pulmonary rehabilitation interventions that aim to improve functional status of individuals, both in the pre- and (longer-term) postoperative period. While there is increased interest in (p)rehabilitation interventions the majority of thoracic surgery patients are however currently on their own with respect to progression of their exercise and physical activity regimens after they have been discharged from hospital. There are also no formal guidelines supporting the referral of these patients to outpatient rehabilitation programs. The current evidence regarding rehabilitation interventions initiated before, during, and after the hospitalization period will be briefly reviewed with special focus on patients undergoing surgery for lung cancer treatment and patients undergoing lung transplantation. More research will be necessary in the coming years to modify or change clinical rehabilitation practice beyond the acute admission phase in patients undergoing thoracic surgery. Tele rehabilitation or web-based activity counseling programs might also be interesting emerging alternatives in the (long-term) postoperative rehabilitative treatment of these patients.

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals Pannexin-1 Channels as Mediators of Neuroinflammation

2021 ◽  
Vol 22 (10) ◽  
pp. 5189
Author(s):  
Joon Ho Seo ◽  
Miloni S. Dalal ◽  
Jorge E. Contreras
Keyword(s):  
Immune Cells ◽  
Neurological Diseases ◽  
Atp Release ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Damage Site ◽  
Pannexin 1 ◽  
Cytokines And Chemokines ◽  
Secondary Damage ◽  
Dying Cells

Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer’s disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5′ triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain. Herein, we review the emerging evidence that directly implicates Panx-1 channels in the neuroinflammatory response in the CNS.

scholarly journals Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1585
Author(s):  
Annamaria Paolini ◽  
Rebecca Borella ◽  
Sara De Biasi ◽  
Anita Neroni ◽  
Marco Mattioli ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cells ◽  
Viral Infections ◽  
Virus Entry ◽  
Therapeutic Strategies ◽  
The Other ◽  
Cytokine Storm ◽  
Cytokines And Chemokines ◽  
Cell Death Mechanisms ◽  
The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

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