Inflammatory biomarker, neopterin, enlarges splenic mast-cell-progenitor pool: Prominent impairment of responses in age-related stromal cell-impairment mouse SCI/SAM

Abstract Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of proinflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the BM microenvironment and that the BM stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a+ senescent BM stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML-induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model, we show that by targeting NOX2 we reduced BM stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia-generated NOX2-derived superoxide as a driver of protumoral p16INK4a-dependent senescence in BM stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs that specifically target the “benign” senescent cells that surround and support AML.

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Existence of c-kit Receptor-Positive, Tryptase-Negative, IgE-Negative Cells in Human Allergic Nasal Mucosa: A Candidate for Mast Cell Progenitor

International Archives of Allergy and Immunology ◽

10.1159/000237429 ◽

1997 ◽

Vol 112 (1) ◽

pp. 36-43 ◽

Cited By ~ 13

Author(s):

Shinichi Kawabori ◽

Naoki Kanai ◽

Takuro Tosho ◽

Toshihide Adachi

Keyword(s):

Mast Cell ◽

Nasal Mucosa ◽

Mast Cell Progenitor

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What the future held: Childhood psychosocial adversity is associated with health deterioration through adulthood in a cohort of British women

10.7287/peerj.preprints.213 ◽

2014 ◽

Author(s):

Daniel Nettle

Keyword(s):

Adult Life ◽

Reproductive Period ◽

Dependent Manner ◽

Inflammatory Biomarker ◽

Individual Level ◽

Physical Decline ◽

Reactive Protein ◽

Simple Index ◽

Age Related ◽

Psychosocial Adversity

Childhood psychosocial adversity is associated with accelerated onset of reproductive effort in women. Adaptive explanations for this phenomenon are built on the assumption that greater childhood psychosocial adversity is statistically associated with having a shorter period of healthy adult life during which reproduction will be possible. However, this critical assumption is never actually tested using individual-level longitudinal data. In this study, I revisit a large, longitudinally-studied cohort of British women. In an earlier paper, we showed that a simple index of psychosocial adversity in the first seven years of life predicted age at first pregnancy in a dose-dependent manner. Here, I show that the same index of adversity also predicts accelerated deterioration of health across the potentially reproductive period, and increased levels of the inflammatory biomarker c-reactive protein at age 44-46. These associations are robust to controlling for adult socioeconomic position, and do not appear to be solely a consequence of accelerated reproductive schedule. I argue that childhood psychosocial adversity may cause latent somatic damage that will, in adulthood, accelerate age-related physical decline. This provides a compelling adaptive rationale for the accelerated reproductive schedules observed in women who experience childhood psychosocial adversity.

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Colloidal SERS sensors for inflammatory biomarker detection in urine for patient risk stratification

10.33774/chemrxiv-2021-bsx14 ◽

2021 ◽

Author(s):

Rachel Kidd ◽

William Anderson ◽

Josh Prince ◽

Akosua Agyemang-Prempeh ◽

Peter Roach ◽

...

Keyword(s):

Inflammatory Marker ◽

Ease Of Use ◽

Risk Category ◽

Sample Treatment ◽

Complex Data ◽

Inflammatory Biomarker ◽

Minimal Sample ◽

Age Related ◽

Increased Risk ◽

Analytical Approaches

Consistently raised levels of inflammatory marker - Neopterin, in urine is linked to increased risk of progression of age-related disease and poorer prognosis. We have developed colloidal SERS sensors and demonstrate their ability, and ease of use, for quantification of neopterin in human urine samples. Results with the sensors are comparable and in agreement with those obtained by HPLC and allow individuals to be stratified into ‘risk’ categories based on their results. With an average 17.85% difference in results between the two analytical approaches, SERS with colloidal sensors, demonstrates an alternative method that is rapid, inexpensive, requires minimal sample treatment, can be performed on a portable instrument with little need for complex data analysis, whilst having the analytical strength to reliably demonstrate an individual’s risk category based on inflammatory load.

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Aqueous humor levels of vascular endothelial growth factor and stromal cell-derived factor-1α in age-related macular degeneration

Beyoglu Eye Journal ◽

10.14744/bej.2021.49140 ◽

2021 ◽

Author(s):

ali keles

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Macular Degeneration ◽

Aqueous Humor ◽

Stromal Cell ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Age Related ◽

Stromal Cell Derived Factor ◽

Endothelial Growth Factor

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Mesenchymal Stromal Cell Therapy For Critically Ill Patients With COVID-19 (Preprint)

10.2196/preprints.20206 ◽

2020 ◽

Author(s):

Koray Yalcin ◽

Cansu Hemsinlioglu ◽

Rehile Zengin ◽

Meral Sonmezoglu ◽

Riza Hakan Erbay ◽

...

Keyword(s):

Mechanical Ventilation ◽

Mesenchymal Stromal Cell ◽

Stromal Cell ◽

Specific Treatment ◽

Intravenous Route ◽

The Novel ◽

Inflammatory Biomarker ◽

Reactive Protein ◽

Advanced Stages ◽

Novel Coronavirus

UNSTRUCTURED The novel coronavirus disease 2019 (COVID-19) continues to spread over the world and there is still no specific treatment. Beside many drug studies, there is not enough data about the place of cellular therapies. In this study, we used second passage cGMP grade umbilical cord-derived Mesenchymal Stromal Cell (MSC) via a combined intratracheal/intravenous route as a novel administration protocol. After the treatment, the values of inflammatory biomarker C-reactive protein of all patients decreased significantly [(before MSC therapy, mean: 84,8 mg/L (2,4-272 mg/L); after MSC administration, mean: 6,5 mg/L (0,3-25,3 mg/L)], procalcitonin decreased for 6 of 7 patients, increasing lymphocyte count was detected in 5 of 7 patients and pulmonary functions PaO2/FiO2 and Positive End-Expiratory Pressure (PEEP) improved in 5 of 7 patients within 7 days after MSC therapy. At the time of MSC administration, all 7 patients were receiving mechanical ventilation. After MSC therapy, 4 of 7 patients were weaned from mechanical ventilation. Although this study has limitations, the outcomes are promising for the advanced stages of COVID-19 pneumonia.

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