Article
Genetics & Heredity
Xiuqin Bao, Danqing Qin, Jicheng Wang, Jing Chen, Cuize Yao, Jie Liang, Kailing Liang, Yixia Wang, Yousheng Wang, Li Du, Aihua Yin
Summary: This study identified two novel deletion mutations in two unrelated families with beta-thalassemia, expanding the spectrum of variants in the Chinese population and providing theoretical guidance for prenatal diagnosis.
Article
Medical Laboratory Technology
Jianlong Zhuang, Chunnuan Chen, Wanyu Fu, Yuanbai Wang, Qianmei Zhuang, Yulin Lu, Tiantian Xie, Ruofan Xu, Shuhong Zeng, Yuying Jiang, Yingjun Xie, Gaoxiong Wang
Summary: Comprehensive analysis of thalassemia alleles based on third-generation sequencing (TGS) can effectively detect both deletional and nondeletional thalassemia variants. This study demonstrates the application value of TGS-based comprehensive analysis in detecting rare thalassemia gene variants.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2023)
Article
Medicine, Research & Experimental
Hanan Kamel M. Saad, Wan Rohani Wan Taib, Imilia Ismail, Muhammad Farid Johan, Abdullah Saleh Al-Wajeeh, Hamid Ali Nagi Al-Jamal
Summary: The study revealed that HEPC levels were significantly decreased while FPN1 levels were markedly increased in HbE/beta-thalassemia patients and their parents, along with elevated serum ferritin levels. This suggests that decreased HEPC function as a negative regulator of FPN1 may result in iron overload in these patients. Assessing HEPC and FPN1 gene expression could be a useful tool to evaluate the risk of iron toxicity and may serve as a therapeutic target for managing iron burden in individuals with HbE/beta-thalassemia.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Carla Casu, Alison Liu, Gianluca De Rosa, Audrey Low, Aae Suzuki, Sayantani Sinha, Yelena Z. Ginzburg, Charles Abrams, Mariam Aghajan, Shuling Guo, Stefano Rivella
Summary: Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm caused by a driver mutation in the JAK2 gene, leading to overproduction of mature erythrocytes and high hematocrit levels. Therapeutic phlebotomy is the standard treatment, but using antisense oligonucleotides against Tmprss6 mRNA to increase hepcidin could provide a less invasive alternative for PV patients.
Article
Physiology
Alkmini T. Anastasiadi, Vassilis L. Tzounakas, Monika Dzieciatkowska, Vasiliki-Zoi Arvaniti, Effie G. Papageorgiou, Issidora S. Papassideri, Konstantinos Stamoulis, Angelo D'Alessandro, Anastasios G. Kriebardis, Marianna H. Antonelou
Summary: The broad spectrum of beta-thalassemia mutations results in heterogeneity in RBC storability profiles, with mutations that slightly affect globin chain equilibrium leading to RBC phenotypes closer to the average control.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Karoline Kuchenbaecker, Arthur Gilly, Daniel Suveges, Lorraine Southam, Olga Giannakopoulou, Britt Kilian, Emmanouil Tsafantakis, Maria Karaleftheri, Aliki-Eleni Farmaki, Deepti Gurdasani, Kousik Kundu, Manjinder S. Sandhu, John Danesh, Adam Butterworth, Ines Barroso, George Dedoussis, Eleftheria Zeggini
Summary: In this study, the role of genetic variation in shaping haematological traits in two isolated Mediterranean populations was examined. Whole-genome sequencing data was used to identify novel associations between rare non-coding variants and haematological traits. The study also found a high diversity of mutational spectrum in the Haemoglobin Subunit Beta (HBB) gene and discovered additional rare variants outside of HBB that play a role in haematological traits.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Hou Qian, Weifeng Li, Xiuhua Lin, Ji Xu, Xiaoli Zhang, Weihua Zhao, Yike Wu, Wenlan Liu
Summary: A 15-year-old girl with severe thalassemia intermedia was found to have a compound heterozygous state of Chinese (G)gamma(+)((A)gamma delta beta)(0)/beta(CD17)-thalassemia combined with a -(SEA) deletion. Molecular analysis revealed that the proband inherited the mutations from her mother and father, with the father carrying a HBB heterozygous mutation and the mother being a double heterozygous carrier of the Chinese (G)gamma(+)((A)gamma delta beta)(0)-thalassemia mutation combined with a -(SEA) deletion. The proband experienced a worsening of clinical symptoms, from no obvious clinical symptoms to severe anemia and splenomegaly, and became dependent on monthly blood transfusions.
MOLECULAR MEDICINE REPORTS
(2023)
Review
Medicine, General & Internal
Raffaella Colombatti, Inga Hegemann, Morten Medici, Camilla Birkegard
Summary: Sickle cell disease is a genetic disorder with a high prevalence in sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. A systematic literature review identified 115 publications on SCD epidemiology, showing highest prevalence in Africa, the Middle East, and India, and lowest in Europe. The study revealed a lack of systematic knowledge and the need for uniform data collection on SCD prevalence and mortality.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Haokun Zhang, Ruilin Sun, Jian Fei, Hongyan Chen, Daru Lu
Summary: This study demonstrates the successful correction of a β-thalassemia mutation using prime editing, which restored the normal phenotype and proved the genomic safety of PE3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Panagiotis Antoniou, Giulia Hardouin, Pierre Martinucci, Giacomo Frati, Tristan Felix, Anne Chalumeau, Letizia Fontana, Jeanne Martin, Cecile Masson, Megane Brusson, Giulia Maule, Marion Rosello, Carine Giovannangeli, Vincent Abramowski, Jean-Pierre De Villartay, Jean-Paul Concordet, Filippo Del Bene, Wassim El Nemer, Mario Amendola, Marina Cavazzana, Anna Cereseto, Oriana Romano, Annarita Miccio
Summary: Sickle cell disease and beta-thalassemia can be treated by editing the HBG promoters to induce gamma-globin expression. This approach is safe and leads to reactivation of fetal hemoglobin and rescue of the pathological phenotype in patient hematopoietic stem/progenitor cells. Creating a binding site for the KLF1 activator is the most potent strategy.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Neha Singh, Nilotpal Chowdhury, Anupama Bahadur, Sana Ahuja, Kunnumbrath Arathi, Reshma Jeladharan, Anissa A. Mirza, Arvind K. Gupta, Harish Chandra, Shalinee Rao
Summary: Thalassemia and hemoglobinopathies are common inherited hematological disorders. This study aimed to determine the prevalence and spectrum of these disorders among antenatal women in Uttarakhand, India. The results showed a prevalence of 2.6% for beta thalassemia trait (BTT) and 0.2% for hemoglobin D-Punjab trait. Red cell indices, including RBC count, MCV, and MCH, were found to be moderately strong predictors of BTT. Routine screening is recommended in this region to detect carriers early in pregnancy.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Physiology
Lourdes Mendez-Mora, Maria Cabello-Fusares, Josep Ferre-Torres, Carla Riera-Llobet, Elena Krishnevskaya, Claudia Trejo-Soto, Salvador Payan-Pernia, Ines Hernandez-Rodriguez, Cristian Morales-Indiano, Tomas Alarcon, Joan-Lluis Vives-Corrons, Aurora Hernandez-Machado
Summary: This study aims to develop a hematocrit-independent method for detecting beta-thalassemia trait and iron deficiency anemia by rheological characterization of whole blood samples, forming the basis for developing a diagnosis and follow-up device. Viscosity is calculated by detecting the advancing fluid-air interface and a mathematical model is introduced to classify different blood conditions. The viscosity varies depending on various RBC factors and is compared to the gold-standard method for validation of clinical value.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Hematology
Yaoyun Li, Yaqing Zhang, Lang Qin, Hangning Shang, Pingping Li, Bin Xiao, Yuhua Ye, Xiangmin Xu, Xinhua Zhang, Li Wang
Summary: In this study, clinical data of 2,130 thalassemia patients were analyzed, revealing a significantly higher splenectomy rate in patients with hemoglobin H (HbH) disease compared to β-thalassemia patients, as well as a significantly older age at diagnosis for HbH disease patients. These findings provide important insights for the clinical management of patients with different types of thalassemia.
ACTA HAEMATOLOGICA
(2023)
Article
Biochemical Research Methods
Christina Lisk, Francesca Cendali, Saini Setua, Kiruphararan Thangaraju, David I. I. Pak, Delaney Swindle, Monika Dzieciatkowska, Fabia Gamboni, Kathryn Hassell, Rachelle Nuss, Gemlyn George, Pavel Davizon-Castillo, Paul W. W. Buehler, Angelo D'Alessandro, David C. C. Irwin
Summary: Sickle cell disease and beta-thalassemia are hemoglobinopathies caused by dysfunctional or underproduced beta-globin chains. The polarization and reprogramming of macrophages in tissue compartments may be relevant to disease progression. Mouse models of beta-globinopathy provide insights into the mechanisms and translation to human disease. A multi-omics approach was used to study macrophage metabolism and protein changes in two murine models, revealing distinct phenotypes and disease-specific reprogramming in different tissue compartments.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Medicine, General & Internal
Vineeta Gupta, Priyanka Aggarwal
Summary: HbD disease was identified in 31 samples from 15 families out of the 2560 samples analyzed. There were variable clinical presentations for patients with HbSD and HbDI3 disease, with some requiring blood transfusions and others being asymptomatic. Individuals with HbD trait were either asymptomatic or had mild anemia.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J. Blom, Frederick J. Raal, Marina Cuchel
Summary: Patients with homozygous familial hypercholesterolaemia (HoFH) globally face issues of late diagnosis, under-treatment, and high risk of premature ASCVD. The use of multiple lipid-lowering therapy regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival.
Article
Biochemistry & Molecular Biology
Valeria Iobbi, Paola Brun, Giulia Bernabe, Romeo Arago Dougue Kentsop, Giuliana Donadio, Barbara Ruffoni, Paola Fossa, Angela Bisio, Nunziatina De Tommasi
Summary: The antimicrobial compounds sclareol and manool extracted from Salvia tingitana may act as potential quorum-sensing inhibitors against methicillin-resistant Staphylococcus aureus, with sclareol showing synergistic activity with clindamycin. The quantification of these compounds in plant tissues revealed that sclareol is most abundant in flower spikes, while manool is predominantly found in roots. Additionally, docking simulations suggested that these compounds may prevent the binding of AgrA to DNA or its activation upon phosphorylation, suppressing the expression of virulence factors.
Article
Biochemistry & Molecular Biology
Valeria Iobbi, Anna Paola Lanteri, Andrea Minuto, Valentina Santoro, Giuseppe Ferrea, Paola Fossa, Angela Bisio
Summary: Tomato brown rugose fruit virus (ToBRFV) is a new damaging plant virus with no resistant cultivars. 4-hydroxybenzoic acid from the methanolic extract of C. micranthum leaves was found to effectively degrade the virus particles. In vitro experiments and molecular docking simulation showed the potential antiviral activity of 4-hydroxybenzoic acid and catechinic acid.
Article
Chemistry, Medicinal
Elena Cichero, Alessio Calautti, Valeria Francesconi, Michele Tonelli, Silvia Schenone, Paola Fossa
Summary: Targeting the fusion (F) protein is a recognized strategy for developing anti-RSV agents, with benzimidazole-containing derivatives showing promise in clinical trials. Computational studies based on X-ray crystallographic data of RSV F protein revealed key contacts supporting the benzimidazole F protein inhibitor ability. The results emphasized the importance of hydrophobic interactions, pi-pi stacking, and H-bonding in the binding ability of benzimidazole F protein inhibitors.
Article
Cardiac & Cardiovascular Systems
Cristina Pederiva, Maria Elena Capra, Giacomo Biasucci, Giuseppe Banderali, Enrico Fabrizi, Marta Gazzotti, Manuela Casula, Alberico L. Catapano
Summary: This study aimed to evaluate the association between Lp(a) plasma levels and family history of premature cardiovascular disease in children with familial hypercholesterolaemia. The results showed that subjects with Lp(a) > 30 mg/dl were more likely to have a positive family history of pCVD.
Article
Cardiac & Cardiovascular Systems
Tommaso Fasano, Chiara Trenti, Emanuele A. Negri, Vincenzo Guiducci, Marco Foracchia, Efrem Bonelli, Simone Canovi, Giulia Besutti, Stefano Bertolini, Sebastiano Calandra
Summary: This study successfully identified individuals with a high probability of having FH using data from laboratory and cardiology databases. However, the attainment of lipid goals was largely suboptimal.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Article
Cardiac & Cardiovascular Systems
Elena Olmastroni, Marta Gazzotti, Marcello Arca, Maurizio Averna, Angela Pirillo, Alberico Luigi Catapano, Manuela Casula
Summary: The study evaluated the distribution of polygenic hypercholesterolemia in individuals clinically diagnosed with FH but without disease-causing mutations. The results showed a positive correlation between the polygenic LDL-C risk score and FH mutations, suggesting that this score can be used to identify patients with polygenic hypercholesterolemia.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Pharmacology & Pharmacy
Livia Pisciotta, Alice Ossoli, Annalisa Ronca, Anna Garuti, Raffaele Fresa, Elda Favari, Laura Calabresi, Sebastiano Calandra, Stefano Bertolini
Summary: This study characterized the phenotypic and genotypic features of a family with primary hyperalphalipoproteinemia (HALP). The results showed alterations in HDL composition and subclass distribution, as well as functional changes affecting cholesterol efflux capacity of serum, suggesting a defect in the early steps of reverse cholesterol transport.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Pasqualina D'Ursi, Paola Fossa
Article
Hematology
Anna E. Bortnick, Petra Buzkova, James Otvos, Majken Jensen, Michael Y. Tsai, Matthew Budoff, Rachel Mackey, Samar R. El Khoudary, Elda Favari, Ryung S. Kim, Carlos J. Rodriguez, George Thanassoulis, Jorge R. Kizer
Summary: This study found that high-density lipoprotein (HDL) cholesterol, HDL particle number and size, apoC3-defined HDL subtypes were inversely associated with the long-term incidence and progression of aortic valve calcification (AVC). Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Annalisa Ronca, Nicoletta Pellegrini, Giuditta Pagliai, Monica Dinu, Matteo Manfredini, Matteo Incerti, Elda Favari, Francesco Sofi
Summary: This study aimed to evaluate the effect of Mediterranean diet (MD) and lacto-ovo-vegetarian diet (VD) on HDL function in healthy subjects at low-to-moderate cardiovascular disease (CVD) risk. The results showed that MD was more effective than VD in promoting cholesterol efflux and reducing the concentration of pro-atherogenic lipoproteins, suggesting that MD may be a better therapeutic strategy for cardiovascular prevention.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Naomi Scarano, Elena Abbotto, Francesca Musumeci, Annalisa Salis, Chiara Brullo, Paola Fossa, Silvia Schenone, Santina Bruzzone, Elena Cichero
Summary: This article focuses on the selective inhibitors of SIRT2 enzyme. By using SBVS method, a potential molecular scaffold for designing new SIRT2 inhibitors was identified. Experimental results showed that this molecular scaffold exhibited strong SIRT2 inhibitory activity, validating the effectiveness of the research strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Manuela Casula, Marta Gazzotti, Maria Elena Capra, Elena Olmastroni, Federica Galimberti, Alberico L. Catapano, Cristina Pederiva
Summary: The diagnosis of familiar hypercholesterolemia (FH) in children is limited due to the lower prevalence of typical FH features compared to adults. Collecting more comprehensive data, including information about second-degree relatives, can improve the diagnosis of FH at a younger age.
Article
Nutrition & Dietetics
Cristina Pederiva, Marta Gazzotti, Marcello Arca, Maurizio Averna, Giuseppe Banderali, Giacomo Biasucci, Marta Brambilla, Paola Sabrina Buonuomo, Paolo Calabro, Francesco Cipollone, Nadia Citroni, Sergio D'Addato, Maria Del Ben, Simonetta Genovesi, Ornella Guardamagna, Gabriella Iannuzzo, Lorenzo Iughetti, Giuseppe Mandraffino, Lorenzo Maroni, Giuliana Mombelli, Sandro Muntoni, Fabio Nascimbeni, Angelina Passaro, Fabio Pellegatta, Matteo Pirro, Livia Pisciotta, Roberta Pujia, Riccardo Sarzani, Roberto Scicali, Patrizia Suppressa, Sabina Zambon, Maria Grazia Zenti, Sebastiano Calandra, Alberico Luigi Catapano, Patrizia Tarugi, Federica Galimberti, Manuela Casula, Maria Elena Capra
Summary: Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is crucial for reducing morbidity and mortality. This study investigated the current clinical approach to the management and treatment of pediatric patients with suspected FH in Italian lipid clinics, revealing some differences among centers but overall adherence to the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents.
Article
Biochemistry & Molecular Biology
Paola Fossa, Matteo Uggeri, Alessandro Orro, Chiara Urbinati, Alessandro Rondina, Maria Milanesi, Nicoletta Pedemonte, Emanuela Pesce, Rita Padoan, Robert C. Ford, Xin Meng, Marco Rusnati, Pasqualina D'Ursi
Summary: Nicotinamide (NAM) was found to bind to F508del-CFTR and enhance the therapeutic effect of drugs used for the treatment of cystic fibrosis. This study provides hope for the identification of natural small molecules for the treatment of cystic fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)