scholarly journals Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective

2021 ◽  
Vol 9 (4) ◽  
pp. 759
Author(s):  
Aikaterini Poulaki ◽  
Evangelia-Theophano Piperaki ◽  
Michael Voulgarelis
Keyword(s):  
Bone Marrow ◽  
Full Range ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Parasitic Diseases ◽  
Host Interactions ◽  
Hypoxia Inducible Factor 1 ◽  
Pathway Function ◽  
Parasite Biology ◽  
Genus Leishmania

The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions remains unclear, recent advances are improving our comprehension of VL pathophysiology. In this review we explore the differences in VL immunobiology between the liver and the spleen, leading to contrasting infection outcomes in the two organs, specifically clearance of the parasite in the liver and failure of the spleen to contain the infection. Based on parasite biology and the mammalian immune response, we describe how hypoxia-inducible factor 1 (HIF1) and the PI3K/Akt pathway function as major determinants of the observed immune failure. We also summarize existing knowledge on pancytopenia in VL, as a direct effect of the parasite on bone marrow health and regenerative capacity. Finally, we speculate on the possible effect that manipulation by the parasite of the PI3K/Akt/HIF1 axis may have on the myelodysplastic (MDS) features observed in VL.

Stabilization of hypoxia-inducible factor-1 enhances proangiogenic potential of bone marrow–derived mesenchymal stem cells

2009 ◽  
Vol 209 (3) ◽  
pp. S88
Author(s):  
Sae Hee Ko ◽  
Denise A. Chan ◽  
Jason P. Glotzbach ◽  
Amato J. Giaccia ◽  
Geoffrey C. Gurtner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Substance P aggravates periodontitis by  upregulating HIF-1 α and RANKL / OPG ratio

2019 ◽  
Author(s):  
Kaixian Yan ◽  
Qin Lin ◽  
Kailiang Tang ◽  
Shuang Liu ◽  
Yi Du ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Substance P ◽  
Hypoxia Inducible Factor ◽  
Gingival Fibroblasts ◽  
Normal Tissues ◽  
Hypoxia Inducible Factor 1 ◽  
Receptor Activator ◽  
Porphyromonas Gingivalis Lipopolysaccharide ◽  
Trap Staining ◽  
The Relationship

Abstract Background Both substance P (SP) and hypoxia-inducible factor 1 alpha (HIF-1α) get involved in inflammation and angiogenesis. But the interrelation between SP and HIF-1α in rat periodontitis is still little known. Methods Ligation‐induced rat periodontitis was established to observe the expression of SP and HIF-1α by immunohistochemistry. Gingival fibroblasts and bone marrow macrophages (BMMs) were respectively cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). 10 nM SP with or without 1µg/ml LPS was added to elaborate the relationship between SP and HIF-1α in gingival fibroblasts. The effect of SP on osteoclastogenesis was tested by TRAP staining. Western blotting was applied to investigate the expressions of HIF-1α, osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL). Results The expression levels of HIF-1α and SP were higher in periodontitis than normal tissues. SP could upregulate the level of HIF-1α and RANKL/OPG ratio in LPS-stimulated gingival fibroblasts. SP with or without LPS also facilitated RANKL induced osteoclastogenesis. Conclusion Substance P aggravates periodontitis by increasing HIF-1α and RANKL / OPG ratio.

scholarly journals Exploiting the Role of Hypoxia-Inducible Factor 1 and Pseudohypoxia in the Myelodysplastic Syndrome Pathophysiology

2021 ◽  
Vol 22 (8) ◽  
pp. 4099
Author(s):  
Ioanna E. Stergiou ◽  
Konstantinos Kambas ◽  
Aikaterini Poulaki ◽  
Stavroula Giannouli ◽  
Theodora Katsila ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hypoxia Inducible Factor ◽  
Aberrant Expression ◽  
Myeloid Lineage ◽  
Hematopoietic Stem ◽  
Transcription Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Abnormal Mitochondria

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem (HSCs) and/or progenitor cells disorders. The established dependence of MDS progenitors on the hypoxic bone marrow (BM) microenvironment turned scientific interests to the transcription factor hypoxia-inducible factor 1 (HIF-1). HIF-1 facilitates quiescence maintenance and regulates differentiation by manipulating HSCs metabolism, being thus an appealing research target. Therefore, we examine the aberrant HIF-1 stabilization in BMs from MDS patients and controls (CTRLs). Using a nitroimidazole–indocyanine conjugate, we show that HIF-1 aberrant expression and transcription activity is oxygen independent, establishing the phenomenon of pseudohypoxia in MDS BM. Next, we examine mitochondrial quality and quantity along with levels of autophagy in the differentiating myeloid lineage isolated from fresh BM MDS and CTRL aspirates given that both phenomena are HIF-1 dependent. We show that the mitophagy of abnormal mitochondria and autophagic death are prominently featured in the MDS myeloid lineage, their severity increasing with intra-BM blast counts. Finally, we use in vitro cultured CD34+ HSCs isolated from fresh human BM aspirates to manipulate HIF-1 expression and examine its potential as a therapeutic target. We find that despite being cultured under 21% FiO2, HIF-1 remained aberrantly stable in all MDS cultures. Inhibition of the HIF-1α subunit had a variable beneficial effect in all <5%-intra-BM blasts-MDS, while it had no effect in CTRLs or in ≥5%-intra-BM blasts-MDS that uniformly died within 3 days of culture. We conclude that HIF-1 and pseudohypoxia are prominently featured in MDS pathobiology, and their manipulation has some potential in the therapeutics of benign MDS.

scholarly journals Cysteine-Rich Angiogenic Inducer 61: Pro-Survival Function and Role as a Biomarker for Disseminating Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 563
Author(s):  
Kai Bartkowiak ◽  
Isabel Heidrich ◽  
Marcel Kwiatkowski ◽  
Tobias M. Gorges ◽  
Antje Andreas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Bone Marrow Cells ◽  
Survival Function ◽  
Hypoxia Inducible Factor ◽  
Breast Cancer Patients ◽  
Hypoxia Inducible Factor 1

(1) Background: the early detection of cancer cells in the blood or bone marrow of breast cancer patients improves the understanding of metastasis. Disseminating tumor cells in the bone marrow with a pronounced manifestation of mesenchymal markers (mDTC) are difficult to detect by epithelial markers, but they are relevant in the initiation of metastasis. (2) Methods: the breast cancer mDTC cell line BC-M1 was analyzed by mass spectrometry, which revealed high levels of the protein-cysteine–rich angiogenic inducer 61 (Cyr61). The function of Cyr61 was investigated using shRNA and hypoxia. Peripheral blood samples from 35 breast cancer patients were investigated for CTCs defined as cytokeratin-positive/CD45-negative cells. (3) Results: the Cyr61 levels are elevated in mDTC lines from breast, lung, and prostate cancer patients. The loss of Cyr61 resulted in the diminished expression of hypoxia-inducible factor 1-alpha, and increased apoptosis. Cyr61 was present in 47 (43%) of the 109 detected circulating tumor cells (CTCs), while the blood and bone marrow cells from healthy controls were Cyr61-negative. (4) Conclusions: Cyr61 is expressed in mDTC lines, supports the viability of cancer cells, and classifies a new subset of cytokeratin-positive CTCs, which deserves further investigation.

scholarly journals Uveitis associated to the infection by Leishmania chagasi in dog from the Olinda city, Pernambuco, Brazil

2004 ◽  
Vol 34 (3) ◽  
pp. 925-929 ◽  
Author(s):  
Fábio Luiz da Cunha Brito ◽  
Leucio Câmara Alves ◽  
Juan Pablo Duque Ortiz ◽  
Federico Celso Lyra Maia ◽  
Valdemiro Amaro da Silva Junior ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Canine Leishmaniasis ◽  
Parasitic Diseases ◽  
Canine Visceral Leishmaniasis ◽  
Leishmania Chagasi ◽  
Parasitological Diagnosis ◽  
Ocular Lesions ◽  
Ocular Signs

Among the parasitic diseases, Canine Visceral Leishmaniasis (CVL) is included in the systemic illnesses of chronic evolution that attack men and dogs, presenting varied clinical manifestations as cachexia, dermatologic lesions, peripheral lymphadenopathies, besides the ocular lesions. This work report the case of a dog clinically suspected of having CVL, presenting skin lesions, cachexia, gryphosis, and ocular signs of uveitis. The parasitological diagnosis was accomplished for Canine Leishmaniasis through the visualization of amastigote forms of Leishmania chagasi in smears of bone marrow fluid aspirate, of non-lesioned, and lesioned skin. Alterations in the ocular structures are characterized mainly by mononuclear-plasmocitic infiltrate.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

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