scholarly journals Harnessing the Potential of miRNAs in Malaria Diagnostic and Prevention

2021 ◽  
Vol 11 ◽  
Author(s):  
Himanshu Gupta ◽  
Samuel C. Wassmer
Keyword(s):  
Organ Dysfunction ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Positive Outcome ◽  
Organ Damage ◽  
Severe Form ◽  
Parasitic Infections ◽  
Specific Organ ◽  
Clinical Models ◽  
Future Evaluation

Despite encouraging progress over the past decade, malaria remains a major global health challenge. Its severe form accounts for the majority of malaria-related deaths, and early diagnosis is key for a positive outcome. However, this is hindered by the non-specific symptoms caused by malaria, which often overlap with those of other viral, bacterial and parasitic infections. In addition, current tools are unable to detect the nature and degree of vital organ dysfunction associated with severe malaria, as complications develop silently until the effective treatment window is closed. It is therefore crucial to identify cheap and reliable early biomarkers of this wide-spectrum disease. microRNAs (miRNAs), a class of small non-coding RNAs, are rapidly released into the blood circulation upon physiological changes, including infection and organ damage. The present review details our current knowledge of miRNAs as biomarkers of specific organ dysfunction in patients with malaria, and both promising candidates identified by pre-clinical models and important knowledge gaps are highlighted for future evaluation in humans. miRNAs associated with infected vectors are also described, with a view to expandind this rapidly growing field of research to malaria transmission and surveillance.

scholarly journals Diabetic Ketoacidosis Presenting in Major Thalassemia With Pancreatic Hemosiderosis: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A376-A376
Author(s):  
Calvin Kurnia Mulyadi ◽  
Bonita Effendi ◽  
Robby Pratomo ◽  
Pratiwi Kesuma ◽  
Dicky Levenus Tahapary
Keyword(s):  
Diabetic Ketoacidosis ◽  
Wide Spectrum ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Current Evidence ◽  
First Episode ◽  
Prior History ◽  
Reduced Ejection Fraction ◽  
T2 Mri

Abstract Introduction: Iron overload is a common complication of thalassemia, responsible for multiple organ damage, including pancreas. The prevalence of diabetes in thalassemia was 9.7–29%,1 while the incidence of diabetic ketoacidosis (DKA) is only 0,3%.2 Case Illustration: A 26 year-old male with thalassemia major (TM) admitted due to dyspnea, which later revealed as first episode of DKA. No prior history of hyperglycemia, but the patient has unexplained weight loss. He receives combination of chelators (deferiprone, desferroxamine, deferriprox) with ferritin level 8,387 μg/mL. Serum glucose was remarkably high (690 mg/dL), with ketosis (4.2 μg/dL) and metabolic acidosis (pH 7.2; bicarbonate 5.6 mEq/L). No single insult was identified, but recurrent ventricular tachycardia was documented. T2* MRI demonstrates severe cardiac and mild pancreatic hemosiderosis. Echocardiography shows reduced ejection fraction (25.6%), atrioventricular dilatation, and hypokinetism. Discussion: Impaired glucose metabolism in TM is initially mediated by insulin resistance, but later, the interplay between defect in insulin secretion and resistance determines the various clinical picture of diabetes in TM.3 Several mechanisms have been linked: oxidative stress, induction of autoimmunity, and zinc deficiency; yet, current evidence remains inadequate.4 The T2* MRI provides the most reliable tool to predict the development of glycemic dysregulation, whereas relying solely on ferritin could lead to imprecise measurement of iron deposits.5 The presence of cardiac abnormality might responsible for the DKA and suggests the need of rescue chelation for this patient. Conclusion: DKA is a rare endocrine complications which can be prevented by routine T2* MRI screening and has wide spectrum of clinical characteristics.

scholarly journals Two-faced Janus: the dual role of macrophages in atherosclerotic calcification

2021 ◽  
Author(s):  
Olivia J Waring ◽  
Nikolaos T Skenteris ◽  
Erik A L Biessen ◽  
Marjo M P C Donners
Keyword(s):  
Current Knowledge ◽  
Wide Spectrum ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Macrophage Phenotype ◽  
Phenotypic Changes ◽  
Direct Exposure ◽  
Stable Plaque ◽  
Mechanisms Of Development ◽  
The One

Abstract Calcification is an independent predictor of atherosclerosis-related cardiovascular events. Microcalcification is linked to inflamed, unstable lesions, in comparison to the fibrotic stable plaque phenotype generally associated with advanced calcification. This paradox relates to recognition that calcification presents in a wide spectrum of manifestations that differentially impact plaque’s fate. Macrophages, the main inflammatory cells in atherosclerotic plaque, have a multifaceted role in disease progression. They crucially control the mineralization process, from microcalcification to the osteoid metaplasia of bone-like tissue. It is a bilateral interaction that weighs heavily on the overall plaque fate but remains rather unexplored. This review highlights current knowledge about macrophage phenotypic changes in relation to and interaction with the calcifying environment. On the one hand, macrophage-led inflammation kickstarts microcalcification through a multitude of interlinked mechanisms, which in turn stimulates phenotypic changes in vascular cell types to drive microcalcification. Macrophages may also modulate the expression/activity of calcification inhibitors and inducers, or eliminate hydroxyapatite nucleation points. Contrarily, direct exposure of macrophages to an early calcifying milieu impacts macrophage phenotype, with repercussions for plaque progression and/or stability. Macrophages surrounding macrocalcification deposits show a more reparative phenotype, modulating extracellular matrix, and expressing osteoclast genes. This phenotypic shift favours gradual displacement of the pro-inflammatory hubs; the lipid necrotic core, by macrocalcification. Parallels to bone metabolism may explain many of these changes to macrophage phenotype, with advanced calcification able to show homeostatic osteoid metaplasia. As the targeted treatment of vascular calcification developing in atherosclerosis is thus far severely lacking, it is crucial to better understand its mechanisms of development.

scholarly journals MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1110 ◽  
Author(s):  
Anna Caliò ◽  
Diego Segala ◽  
Enrico Munari ◽  
Matteo Brunelli ◽  
Guido Martignoni
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clinical Course ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Cathepsin K ◽  
World Health ◽  
Epithelioid Angiomyolipoma ◽  
Immunohistochemical Markers

The new category of MiT family translocation renal cell carcinoma has been included into the World Health Organization (WHO) classification in 2016. The MiT family translocation renal cell carcinoma comprises Xp11 translocation renal cell carcinoma harboring TFE3 gene fusions and t(6;11) renal cell carcinoma harboring TFEB gene fusion. At the beginning, they were recognized in childhood; nevertheless, it has been demonstrated that these neoplasms can occur in adults as well. In the nineties, among Xp11 renal cell carcinoma, ASPL, PRCC, and SFPQ (PSF) were the first genes recognized as partners in TFE3 rearrangement. Recently, many other genes have been identified, and a wide spectrum of morphologies has been described. For this reason, the diagnosis may be challenging based on the histology, and the differential diagnosis includes the most common renal cell neoplasms and pure epithelioid PEComa/epithelioid angiomyolipoma of the kidney. During the last decades, many efforts have been made to identify immunohistochemical markers to reach the right diagnosis. To date, staining for PAX8, cathepsin K, and melanogenesis markers are the most useful identifiers. However, the diagnosis requires the demonstration of the chromosomal rearrangement, and fluorescent in situ hybridization (FISH) is considered the gold standard. The outcome of Xp11 translocation renal cell carcinoma is highly variable, with some patients surviving decades with indolent disease and others dying rapidly of progressive disease. Despite most instances of t(6;11) renal cell carcinoma having an indolent clinical course, a few published cases demonstrate aggressive behavior. Recently, renal cell carcinomas with TFEB amplification have been described in connection with t(6;11) renal cell carcinoma. Those tumors appear to be associated with a more aggressive clinical course. For the aggressive cases of MiT family translocation carcinoma, the optimal therapy remains to be determined; however, new target therapies seem to be promising, and the search for predictive markers is mandatory.

scholarly journals Primary Cilium in Cancer Hallmarks

2019 ◽  
Vol 20 (6) ◽  
pp. 1336 ◽  
Author(s):  
Lucilla Fabbri ◽  
Frédéric Bost ◽  
Nathalie Mazure
Keyword(s):  
Cancer Progression ◽  
Primary Cilium ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Cancer Hallmarks ◽  
Mutual Regulation ◽  
Ultrastructure And Function ◽  
And Function ◽  
External Stimuli

The primary cilium is a solitary, nonmotile and transitory appendage that is present in virtually all mammalian cells. Our knowledge of its ultrastructure and function is the result of more than fifty years of research that has dramatically changed our perspectives on the primary cilium. The mutual regulation between ciliogenesis and the cell cycle is now well-recognized, as well as the function of the primary cilium as a cellular “antenna” for perceiving external stimuli, such as light, odorants, and fluids. By displaying receptors and signaling molecules, the primary cilium is also a key coordinator of signaling pathways that converts extracellular cues into cellular responses. Given its critical tasks, any defects in primary cilium formation or function lead to a wide spectrum of diseases collectively called “ciliopathies”. An emerging role of primary cilium is in the regulation of cancer development. In this review, we seek to describe the current knowledge about the influence of the primary cilium in cancer progression, with a focus on some of the events that cancers need to face to sustain survival and growth in hypoxic microenvironment: the cancer hallmarks.

scholarly journals Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1094 ◽  
Author(s):  
Ludovic Jean Wrobel ◽  
Angèle Gayet-Ageron ◽  
Frédérique-Anne Le Gal
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Beta Blockers ◽  
Primary Melanoma ◽  
Progression Free Survival ◽  
Human Melanoma ◽  
Clinical Models ◽  
Melanoma Patients ◽  
Control Disease

Background: The regulation of melanoma by noradrenergic signaling has gain attention since pre-clinical and clinical studies suggested a benefit of using beta-blockers to control disease progression. We need to confirm that human melanoma recapitulates the mechanisms described from pre-clinical models. Methods: The sources and targets of norepinephrine in the microenvironment of 20 human melanoma samples was investigated using immunostaining. The effect of an exposure to beta-blockers on immune cell type distribution and expression of immune response markers was assessed with immunostaining on 212 human primary melanoma. A statistical analysis explored the effect of an exposure to beta-blockers on progression free survival, melanoma related survival, and overall survival on the 286 eligible patients. Results: Tumor cells and macrophages may be a source of norepinephrine in melanoma microenvironment. Tumors from patients exposed to wide spectrum beta-blockers recapitulate the increased infiltration of T-lymphocytes and the increased production of granzyme B observed in pre-clinical models. An exposure to beta-blockers is associated with a better outcome in our cohort of melanoma patients. Conclusion: This study shows the association between an exposure to wide spectrum beta-blockers and markers of an effective anti-tumor immune response as well as the protective effect of beta-blockers in human melanoma patients.

scholarly journals First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: splenic regeneration

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 1951-1953 ◽  
Author(s):  
S Claster ◽  
E Vichinsky
Keyword(s):  
Immune System ◽  
Organ Dysfunction ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Germinal Centers ◽  
Quadrant Pain ◽  
Significant Impairment ◽  
Splenic Regeneration

Much of the morbidity associated with sickle cell anemia (SCA) is due to ongoing infarction resulting in organ dysfunction. Because the spleen is often the first organ damaged in this illness, there is a significant impairment of the immune system in these patients. Hydroxyurea (HU) has been shown to increase fetal hemoglobin (HbF) and decrease painful episodes in patients with this disease. It is unclear whether HU can prevent organ damage. We treated two SCA patients with HU for several years and found evidence of reversal of previously documented splenic dysfunction. Patient no. 1 was treated for 30 months with an increase in HbF to 30%. HU was stopped because of cytopenia. She developed left upper quadrant pain. A splenectomy was performed due to the possibility of splenic abscesses. A pathologic review found no evidence of infection and an enlarged spleen that showed active germinal centers. Patient no. 2 was treated for 24 months with HU before developing splenomegaly. His HbF levels were 25% to 30%, his pit counts averaged 2%, and his liver spleen scans showed uptake. These two cases show that chronic HU therapy may reverse splenic dysfunction in certain patients and suggest that this drug may have efficacy beyond the elimination of pain in SCA.

Endovascular Therapy for Spontaneous Ilio-Iliac Arteriovenous Fistula Due To Iliac Artery Aneurysm Rupture With Multi-Organ Dysfunction

2020 ◽  
Vol 54 (6) ◽  
pp. 519-524
Author(s):  
Muhammad Tipu Rishi ◽  
John Maijub ◽  
S. Keisin Wang ◽  
Andi Peshkepija ◽  
Justin King ◽  
...  
Keyword(s):  
Arteriovenous Fistula ◽  
Organ Dysfunction ◽  
Endovascular Therapy ◽  
Iliac Artery ◽  
Treatment Options ◽  
Artery Aneurysm ◽  
Organ Damage ◽  
Iliac Vein ◽  
Aneurysm Rupture ◽  
Iliac Artery Aneurysm

Iliac artery aneurysms can rarely present with rupture into adjacent iliac vein resulting in arteriovenous fistula leading to acute cardiac failure or multi-organ failure. End-organ damage can be reversed with timely diagnosis and intervention. Endovascular therapy is an attractive option to treat this pathology besides allowing for a quick recovery and mitigating the risk of mortality associated with open surgical treatment options. We report treatment of this pathology with Endovascular repair with preservation of ipsilateral hypogastric artery flow using an iliac branch graft device. The postoperative course was complicated by type 3 endoleak due to the separation of components between iliac branch graft and aortic stent graft with resultant recurrence of the fistula. Additional endovascular techniques, including placement of a venous stent and stent grafts to bridge the components, was used to treat the endoleak. We present this report due to the unique nature of the recurrent arteriovenous fistula, technical complexity, and resultant multi-organ dysfunction.

scholarly journals Isolated Neck Extensor Myopathy Associated With Cervical Spondylosis: A Case Report and Brief Review

2020 ◽  
Vol 13 ◽  
pp. 117954412097784
Author(s):  
Eric Chun-Pu Chu ◽  
Arnold Yu-Lok Wong ◽  
Andy Fu-Chieh Lin
Keyword(s):  
Case Report ◽  
Cervical Spondylosis ◽  
Surgical Intervention ◽  
Wide Spectrum ◽  
Positive Outcome ◽  
Chronic Injury ◽  
Exercise Rehabilitation ◽  
Neurological Conditions ◽  
Myopathic Changes ◽  
Isolated Neck Extensor Myopathy

Dropped head syndrome (DHS) is manifested as the inability to maintain the head in an upright posture. It has been associated with a wide spectrum of myopathies and neurological conditions. Isolated neck extensor myopathy (INEM) is one of many potential causes of DHS. This is a case report of a 72-year-old man who presented with degenerative cervical spondylosis and DHS for 2 years. He had previously failed to achieve a positive outcome to medication, cervical collar and exercise rehabilitation. However, he was able to regain his voluntary head control after a 4-month chiropractic program. It is believed that INEM is caused by isolated myopathic changes from chronic injury and overloading of the cervical muscles. Cervical spondylosis has been attributed as the cause of DHS secondary to denervation of the cervical extensors. While INEM associated with degenerative spondylosis is not medically treatable, manipulative therapies may be adopted before considering surgical intervention.

scholarly journals The Roles of Hedgehog Signaling in Upper Lip Formation

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hiroshi Kurosaka
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Cleft Lip ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Craniofacial Abnormalities ◽  
Facial Growth ◽  
Congenital Diseases ◽  
Orofacial Clefting ◽  
Facial Development

Craniofacial development consists of a highly complex sequence of the orchestrated growth and fusion of facial processes. It is also known that craniofacial abnormalities can be detected in 1/3 of all patients with congenital diseases. Within the various craniofacial abnormalities, orofacial clefting is one of the most common phenotypic outcomes associated with retarded facial growth or fusion. Cleft lip is one of the representative and frequently encountered conditions in the spectrum of orofacial clefting. Despite various mechanisms or signaling pathways that have been proposed to be the cause of cleft lip, a detailed mechanism that bridges individual signaling pathways to the cleft lip is still elusive.Shhsignaling is indispensable for normal embryonic development, and disruption can result in a wide spectrum of craniofacial disorders, including cleft lip. This review focuses on the current knowledge about the mechanisms of facial development and the etiology of cleft lip that are related toShhsignaling.

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