HCV Infection in Thalassemia Syndromes and Hemoglobinopathies: New Perspectives

Maffei, Laura; Sorrentino, Francesco; Caprari, Patrizia; Taliani, Gloria; Massimi, Sara; Risoluti, Roberta; Materazzi, Stefano

doi:10.3389/fmolb.2020.00007

Cited by 17 publications

(15 citation statements)

References 47 publications

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“…The cytotoxic activities of CTX are, nevertheless, pharmacologically diverse. Depending on the dose of CTX, the cell death could be caused by apoptosis or necrosis [ 32 ] mediated through various mechanisms, e.g., mitochondrial fragmentation (CTX binding to cardiolipin) and membrane pore formation (CTX interacting electrostatically with anionic lipids) [ 33 , 34 ]. Earlier studies also showed that some cobra CTXs could elicit cardiotoxicity through disrupting calcium regulation in cardiac muscle cells, thus prolonging membrane depolarization, resulting in systolic heart arrest [ 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus)

Wong

Tan

et al. 2021

Toxins

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The Senegalese cobra, Naja senegalensis, is a non-spitting cobra species newly erected from the Naja haje complex. Naja senegalensis causes neurotoxic envenomation in Western Africa but its venom properties remain underexplored. Applying a protein decomplexation proteomic approach, this study unveiled the unique complexity of the venom composition. Three-finger toxins constituted the major component, accounting for 75.91% of total venom proteins. Of these, cardiotoxin/cytotoxin (~53%) and alpha-neurotoxins (~23%) predominated in the venom proteome. Phospholipase A2, however, was not present in the venom, suggesting a unique snake venom phenotype found in this species. The venom, despite the absence of PLA2, is highly lethal with an intravenous LD50 of 0.39 µg/g in mice, consistent with the high abundance of alpha-neurotoxins (predominating long neurotoxins) in the venom. The hetero-specific VINS African Polyvalent Antivenom (VAPAV) was immunoreactive to the venom, implying conserved protein antigenicity in the venoms of N. senegalensis and N. haje. Furthermore, VAPAV was able to cross-neutralize the lethal effect of N. senegalensis venom but the potency was limited (0.59 mg venom completely neutralized per mL antivenom, or ~82 LD50 per ml of antivenom). The efficacy of antivenom should be further improved to optimize the treatment of cobra bite envenomation in Africa.

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Section: Resultsmentioning

confidence: 99%

A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus)

Wong

Tan

et al. 2021

Toxins

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“…LDs also have a more dynamic role since proteins present in the lipid droplet coat regulate lipid homeostasis, and therefore, LDs play a very important role in the regulation of intracellular lipid storage and lipid metabolism [ 65 ]. Single-strand RNA viruses, including coronaviruses, target LDs during their replication phase [ 66 , 67 ]. Given the role of LDs in viral replication, it has been proposed to use drugs interfering with LDs as therapeutics able to counteract SARS-CoV-2 infection [ 66 , 68 ].…”

Section: Lipid Metabolic Remodelling Of the Host Cellmentioning

confidence: 99%

Dissecting lipid metabolism alterations in SARS-CoV-2

Casari

Manfredi

Metharom

et al. 2021

Progress in Lipid Research

101

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic that has infected over sixteen million people globally. There have been more than two million deaths recorded worldwide, with no end in sight until a vaccine is developed. Current research has centred on different aspects of the virus interaction with cell surface receptors, but more needs to be done to further understand its mechanism of action in order to develop a targeted therapy and a method to control the spread of the virus. Lipids play a crucial role throughout the viral life cycle, and viruses are known to exploit lipid signalling and synthesis to affect host cell lipidome. Emerging studies using untargeted metabolomic and lipidomic approaches are providing new insight into the host response to COVID-19 infection. Indeed, metabolomic and lipidomic approaches have identified numerous circulating lipids that directly correlate to the severity of the disease, making lipid metabolism a potential therapeutic target. Circulating lipids play a key function in the pathogenesis of the virus and exert an inflammatory response. A better knowledge of lipid metabolism in the host-pathogen interaction will provide valuable insights into viral pathogenesis and to develop novel therapeutic targets.

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“…4 Moreover, new anti-hepatitis C drugs have remarkably reduced the complications linked to hepatitis C infection, which used to dramatically deteriorate liver iron overload. 5 However, in spite of the outstanding advances in the care of cardiovascular and hepatic complications due to blood transfusions, the management of endocrine complications has been left behind and, nowadays, they are the most frequent and the most resource-draining complications in TDT patients. 3 In addition, serological testing fails to identify high-risk groups and, once occurred, these complications are often irreversible.…”

mentioning

confidence: 99%

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort

et al. 2021

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Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3–13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1–1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1–1.4, P

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HCV Infection in Thalassemia Syndromes and Hemoglobinopathies: New Perspectives

Cited by 17 publications

References 47 publications

A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus)

A Neurotoxic Snake Venom without Phospholipase A2: Proteomics and Cross-Neutralization of the Venom from Senegalese Cobra, Naja senegalensis (Subgenus: Uraeus)

Dissecting lipid metabolism alterations in SARS-CoV-2

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort

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