The Global Burden and Attributable Risk Factors of Chronic Lymphocytic Leukemia in 204 Countries and Territories from 1990 to 2019: Analysis Based on the Global Burden of Disease Study 2019.

Yao, Yanlai; Lin, Xiangjie; Li, Fenglin; Jin, Jie; Wang, Huafeng

doi:10.21203/rs.3.rs-824063/v1

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm and is the commonest adult leukaemia in Western countries with reported incidence rates in the USA and Europe being 4–6 per 100,000/ annually 1 , 2 The clinical outcomes of CLL are extremely heterogeneous, where overall survival (OS) and time-to-first treatment (TTFT) vary drastically across CLL patients 3 . Early need for therapy (short TTFT) and short OS are characteristics of progressive and aggressive form of CLL, whereas late or no need for therapy and long OS are features of indolent form of the disease.…”

Section: Introductionmentioning

confidence: 99%

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia

Alsagaby

Iqbal

Ahmad

et al. 2022

Sci Rep

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Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p < 0.0001) and short overall survival (OS; n = 107, p = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10–16) that associated with early need for therapy (n = 130, p < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: − 10.9 to − 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 107 M−1 to 3.77 × 108 M−1) compared with the native ligand (ΔG: − 10.8, Kd: 8.3 × 107 M−−1). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.

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Section: Introductionmentioning

confidence: 99%

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia

Alsagaby

Iqbal

Ahmad

et al. 2022

Sci Rep

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Obesity Effect on the Course of Abdominal Trauma

et al. 2021

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The aim was to determine the role of obesity in the development of fatal complications and deaths in victims with abdominal trauma. Materials and methods: The study was conducted on the basis of the Department of Polytrauma at the Municipal Health Care Institution of Kharkiv City Council ”O.I. Meshchaninov City Clinical Hospital of Ambulance and Emergency Care”. The authors have analyzed the case histories of 240 patients with abdominal trauma depending on the presence of obesity, which was determined by BMI (body mass index) and/or waist circumference (WC). Results: Complications were found in 93 (38.8%) victims, 34 (14.2%) victims died. It was found that the overall incidence of complications, respiratory and hemocoagulation complications, the incidence of multiple organ failure (MOF) and mortality significantly increased in obese victims. Determination of obesity by the value of the BMI during hospitalization was possible in 41.7% of victims. The identification of WC turned out to be no less informative, but more accessible. Conclusions: Obesity increases the incidence of complications and mortality in victims of abdominal trauma, and is a marker of a negative prognosis. Traditional assessment of BMI during hospitalization in most victims with abdominal trauma is not possible due to the severity of the condition and/or the presence of combined injuries. A good alternative to determining obesity in victims with abdominal trauma is a WC (more than 88 cm in women and more than 102 cm in men).

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Diagnosing Autism Spectrum Disorders in Childhood

Severin

2021

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The Global Burden and Attributable Risk Factors of Chronic Lymphocytic Leukemia in 204 Countries and Territories from 1990 to 2019: Analysis Based on the Global Burden of Disease Study 2019.

Cited by 3 publications

References 13 publications

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia

Obesity Effect on the Course of Abdominal Trauma

Diagnosing Autism Spectrum Disorders in Childhood

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