scholarly journals Loneliness: An Immunometabolic Syndrome

2021 ◽  
Vol 18 (22) ◽  
pp. 12162
Author(s):  
Homa Pourriyahi ◽  
Niloufar Yazdanpanah ◽  
Amene Saghazadeh ◽  
Nima Rezaei
Keyword(s):  
Mental Health ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Cell Activity ◽  
Acute Phase Reactants ◽  
Health Determinant ◽  
Psychological Experience ◽  
It Impacts ◽  
Shared Network ◽  
Detailed Picture

Loneliness has been defined as an agonizing encounter, experienced when the need for human intimacy is not met adequately, or when a person’s social network does not match their preference, either in number or attributes. This definition helps us realize that the cause of loneliness is not merely being alone, but rather not being in the company we desire. With loneliness being introduced as a measurable, distinct psychological experience, it has been found to be associated with poor health behaviors, heightened stress response, and inadequate physiological repairing activity. With these three major pathways of pathogenesis, loneliness can do much harm; as it impacts both immune and metabolic regulation, altering the levels of inflammatory cytokines, growth factors, acute-phase reactants, chemokines, immunoglobulins, antibody response against viruses and vaccines, and immune cell activity; and affecting stress circuitry, glycemic control, lipid metabolism, body composition, metabolic syndrome, cardiovascular function, cognitive function and mental health, respectively. Taken together, there are too many immunologic and metabolic manifestations associated with the construct of loneliness, and with previous literature showcasing loneliness as a distinct psychological experience and a health determinant, we propose that loneliness, in and of itself, is not just a psychosocial phenomenon. It is also an all-encompassing complex of systemic alterations that occur with it, expanding it into a syndrome of events, linked through a shared network of immunometabolic pathology. This review aims to portray a detailed picture of loneliness as an “immunometabolic syndrome”, with its multifaceted pathology.

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

scholarly journals Neurological and mental health consequences of COVID-19: potential implications for well-being and labor force

2021 ◽  
Author(s):  
I B Meier ◽  
C Vieira Ligo Teixeira ◽  
I Tarnanas ◽  
F Mirza ◽  
L Rajendran
Keyword(s):  
Mental Health ◽  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Impairment ◽  
Immune Cell ◽  
Previous History ◽  
Well Being ◽  
Acute Disseminated Encephalomyelitis ◽  
The Central Nervous System ◽  
Neurological Protection

Abstract Recent case studies show that the SARS-CoV-2 infectious disease, COVID-19, is associated with accelerated decline of mental health, in particular, cognition in elderly individuals, but also with neurological and neuropsychiatric illness in young people. Recent studies also show a bidirectional link between COVID-19 and mental health in that people with previous history of psychiatric illness have a higher risk for contracting COVID-19 and that COVID-19 patients display a variety of psychiatric illnesses. Risk factors and the response of the central nervous system to the virus show large overlaps with pathophysiological processes associated with Alzheimer’s disease, delirium, post-operative cognitive dysfunction and acute disseminated encephalomyelitis, all characterized by cognitive impairment. These similarities lead to the hypothesis that the neurological symptoms could arise from neuroinflammation and immune cell dysfunction both in the periphery as well as in the central nervous system and the assumption that long-term consequences of COVID-19 may lead to cognitive impairment in the well-being of the patient and thus in today’s workforce, resulting in large loss of productivity. Therefore, particular attention should be paid to neurological protection during treatment and recovery of COVID-19, while cognitive consequences may require monitoring.

scholarly journals How Changes in the Nutritional Landscape Shape Gut Immunometabolism

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 823
Author(s):  
Jian Tan ◽  
Duan Ni ◽  
Rosilene V. Ribeiro ◽  
Gabriela V. Pinget ◽  
Laurence Macia
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Immune Cell ◽  
Food Additives ◽  
Cell Activity ◽  
Inflammatory Cells ◽  
Therapeutic Approaches ◽  
Food Antigens ◽  
And Function ◽  
Micro Organisms

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

Given the importance of mTOR signaling in a number of illnesses, it looks suitable to use miR 99 family members as a therapeutic intervention to deal with these illnesses by using gene therapy tools

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Therapeutic Intervention ◽  
Regulatory Network ◽  
Immune Cell ◽  
Family Members ◽  
Cell Activity ◽  
Mtor Signaling ◽  
Critical Pathways ◽  
Functional Roles ◽  
Cell Life ◽  
High Level

This review outlines the activities of mirR99 family members in different cancers. Though the functional roles of these miRs are well described in some malignancies, the functional functions of these family members in other forms of cancer remain uncertain. The development and use of engineered mouse models such as miR99a KO, miR100 KO, or miR99a/100 DKO mice challenged with the type or subtype of the cancer in question would be extremely beneficial in determining the physiological and pathological roles of members of this family in different types of cancer and immune cell subtypes.The miR99 family members, which include miR99a, miR99b, and miR100, are key components of a regulatory network that governs several aspects of the cell life cycle, including differentiation, metabolism, survival and death. They are involved in the deregulation of numerous critical pathways including growth factor receptors like FGFR and IGF1R, Notch, mTOR, TGFB and Wnt signaling pathways to alter cellular function. In addition, the typical miR99 target, mTOR, appears to be at the core of the regulatory network miR99, and is more commonly involved in miR99-mediated dysregulation of cell activity. Given the importance of mTOR signaling in a number of illnesses, it looks suitable to use miR99 family members as a therapeutic intervention to deal with these illnesses. mTOR depletion did not result in upregulating miR99a in OSCC cells. In addition, an aberrant activation of PI3K/AKT/mTOR signaling in AMLs, despite increased expression of miR99 family members in AMLs. All in all, this evidence alludes to the existence of an unknown mechanism that maintains mTOR activity running despite the presence in these cells of a high level of miR99 family members. Modulation of miR99 activity might be a viable method for changing the expression of Treg in autoimmune diseases.

A phase II study of atezolizumab (ATEZO) and bevacizumab (Bev) in combination with Y90 TARE in patients (Pts) with hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS358-TPS358
Author(s):  
Aiwu Ruth He ◽  
Alexander Y. Kim ◽  
Beau M Toskich ◽  
Kabir Mody ◽  
Kevin Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Phase Ii ◽  
Immune Cell ◽  
Phase Ii Study ◽  
Cell Activity ◽  
Ct Scans ◽  
Primary Study ◽  
Study Objective ◽  
Patient Reported

TPS358 Background: The anti–PD-L1 antibody ATEZO prevents PD-L1 from interacting with PD-1 and B7.1, thus reinvigorating antitumor T cell activity. Anti-VEGF BEV can increase dendritic cell maturation, enhance T cell infiltration, and reduce myeloid-derived suppressor cells and regulatory T-cells in tumors. This combination has been FDA approved for first-line treatment of advanced HCC based on the IMbrave 150 study. On the other hand, locoregional radiotherapy (e.g., Y90 TARE) enhances the diversity of the intratumoral T cell receptor repertoire. It is the standard of care for pts with intermediate-stage HCC (iHCC). Based on preclinical and clinical data, we hypothesize that the combination of Y90 TARE, BEV, and ATEZO induces synergistic tumor-killing. Methods: This is an open-label, multicenter, randomized phase II study of Y90 TARE and BEV plus ATEZO compared with Y90 TARE alone in pts with unresectable IHCC. The primary study objective is to assess and compare the progression-free survival (PFS) (per mRECIST 1.1) of pts in each arm. The main secondary objective is to determine the safety and tolerability (CTCAE v5) of TARE combined with ATEZO and BEV in pts with HCC. Exploratory objectives are to assess the role of the immunoscore and PD-L1 expression levels in the prediction of improved clinical outcome in pts receiving Y-90 TARE and BEV plus ATEZO; the composition of tumor-infiltrating immune cell subtypes in predicting response to a chosen therapy; how Y90 therapy affects the proportion of antigen-presenting cells in the tumor; and symptoms experienced by pts receiving TARE and BEV plus ATEZO treatment, using patient-reported outcomes. Eligible pts have either HCC that is not amenable to surgical resection, confirmed by pathology review, or at least BCLC stage B HCC outside of downstaging criteria. Other standard eligibility criteria apply. Pts must have a pretreatment liver biopsy taken and then be randomized 1:1 to TARE (Arm A) or TARE followed by ATEZO and BEV (Arm B). Pts will have TARE mapping during week (wk) 1 and TARE treatment during wk 2. In Arm B, pts will start BEV plus ATEZO 4 wks (±1 wk) after TARE treatment. Pts will have abdominal MRI or CT scans every 12 weeks, CT scans of the chest every 24 wks, and a second tumor biopsy at 4 wks. Disease progression will be captured by both RECIST 1.1 and mRECIST. We plan to assess the safety of TARE with BEV and ATEZO in the first 10 pts randomized to Arm B for two cycles. If there are no grade ≥ 3 unexpected toxicities possibly, probably or definitely related to combined TARE plus BEV plus ATEZO, the study will continue to accrue 128 pts in total. Pts will continue study treatment (Arm B) for a total of 24 months from initiation of TARE or until intolerable toxicity or disease progression occur, whichever is earlier. Enrollment began in September 2020. Clinical trial information: NCT04541173.

scholarly journals Manipulation of Glucose Availability to Boost Cancer Immunotherapies

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2940
Author(s):  
Federica Marchesi ◽  
Debora Vignali ◽  
Beatrice Manini ◽  
Alessandra Rigamonti ◽  
Paolo Monti
Keyword(s):  
T Cell ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Immune Cell ◽  
Deep Level ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Cell Function ◽  
Cancer Tissues ◽  
Cancer Immunotherapies

The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathway is central in shaping T cell responses and emerges as an ideal target to improve cancer immunotherapy. However, metabolic manipulation requires a deep level of control over side-effects and development of biomarkers of response. Here, we summarize the metabolic control of T cell function and focus on the implications of metabolic manipulation for the design of immunotherapeutic strategies. Integrating our understanding of T cell function and metabolism will hopefully foster the forthcoming development of more effective immunotherapeutic strategies.

scholarly journals Recent Findings in the Posttranslational Modifications of PD-L1

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Shu-Man Li ◽  
Jie Zhou ◽  
Yun Wang ◽  
Run-Cong Nie ◽  
Jie-Wei Chen ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Immune Checkpoint ◽  
Protein Modification ◽  
Immune Cell ◽  
Response Rate ◽  
Malignant Tumors ◽  
Objective Response ◽  
Cell Activity ◽  
Patients With Cancer ◽  
L1 Protein

Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.

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