Hb D-Los Angeles [beta121(GH4)Glu>Gln] and Hb Beograd [beta121(GH4)Glu>Val]: Implications for their laboratory diagnosis and genetic origins

Objective: The aim of this study was to determine the laboratory diagnosis and genetic origins of the hemoglobin (Hb) variants, Hb D-Los Angeles and Hb Beograd observed frequently in our region. Material and Methods: Hb variants were investigated in one Hb D-Los Angeles and two Hb Beograd families. These families were unrelated with each other. For the determination of Hb variants, alkaline/acid electrophoresis, HPLC, DE-52 micro-column chromatography procedures were applied. Mutations were determined by non-radioactive fluorescence automated DNA sequencing. Beta globin gene cluster haplotypes were identified by RFLP analysis at seven loci known as ε-Hinc II, Gγ-Hind III, Aγ-Hind III, 5′ψβ-Hinc II, 3′ψβ-Hinc II, β-Ava II ve 3′β-Hinf I. Results: Three novel beta globin gene cluster haplotypes were identified as in relation with Hb D-Los Angeles [--+-+++], Hb Beograd [+----++ and -+-(+/-)(+/-)+(+/-)]. These haplotypes were reported for the first time in the world population Conclusion: In this study we emphasize the importance of DNA seqeuncing and other laboratory procedures for the identification of Hb variants in premarital diagnosis. On the other hand we discuss also the genetic origins of these Hb variants

Genetic origin of Hb D-Los Angeles [beta121(GH4)Glu-->Gln, GAA-->CAA] according to the beta-globin gene cluster haplotypes.

Hb D-Los Angeles (also known as D-Punjab, D-North Carolina, D-Portugal, D-Chicago and Oak Ridge) is an abnormal hemoglobin (Hb) with an amino acid substitution of glutamine for glutamic acid at codon 121 of the beta-globin gene. The origin and spread of Hb D-Los Angeles is not known. This is due to lack of information and remains to be elucidated. According to published reports, the Hb D-Los Angeles mutation is mostly linked with Mediterranean haplotype I [+ - - - - + +]. Besides the Mediterranean haplotype, a novel haplotype was also reported from Thailand [- - + + - - + + +]. Here we report a new haplotype from Turkey [- + -- + + +] that has not been described before. These results suggest that the Hb D-Los Angeles mutation has at least three different genetic origins

Genetic origin of Hb D-Los Angeles [β121(GH4)Glu→Gln, GAA→CAA] according to the β-globin gene cluster haplotypes

□ Hb D-Los Angeles (also known as D-Punjab, D-North Carolina, D-Portugal, D-Chicago and Oak Ridge) is an abnormal hemoglobin (Hb) with an amino acid substitution of glutamine for glutamic acid at codon 121 of the β-globin gene. The origin and spread of Hb D-Los Angeles is not known. This is due to lack of information and remains to be elucidated. According to published reports, the Hb D-Los Angeles mutation is mostly linked with Mediterranean haplotype I [+ - - - - + +]. Besides the Mediterranean haplotype, a novel haplotype was also reported from Thailand [- - + + - - + + +]. Here we report a new haplotype from Turkey [- + - + + +] that has not been described before. These results suggest that the Hb D-Los Angeles mutation has at least three different genetic origins. Copyright © Informa Healthcare

Hb D-Los Angeles [beta121(GH4)Glu>Gln] and Hb Beograd [beta121(GH4)Glu>Val]: Implications for their laboratory diagnosis and genetic origins.

OBJECTIVE: The aim of this study was to determine the laboratory diagnosis and genetic origins of the hemoglobin (Hb) variants, Hb D-Los Angeles and Hb Beograd observed frequently in our region. MATERIAL AND METHODS: Hb variants were investigated in one Hb D-Los Angeles and two Hb Beograd families. These families were unrelated with each other. For the determination of Hb variants, alkaline/acid electrophoresis, HPLC, DE-52 micro-column chromatography procedures were applied. Mutations were determined by non-radioactive fluorescence automated DNA sequencing. Beta globin gene cluster haplotypes were identified by RFLP analysis at seven loci known as ε-Hinc II, Gγ-Hind III, AΨβ-Hind III, 5'Ψβ-Hinc II, 3'Ψβ-Hinc II, β-Ava II ve 3'β-Hinf I. RESULTS: Three novel beta globin gene cluster haplotypes were identified as in relation with Hb D-Los Angeles [--+-+++], Hb Beograd [+----++ and -+-(+/-)(+/-)+(+/-)]. These haplotypes were reported for the first time in the world population Conclusion: In this study we emphasize the importance of DNA seqeuncing and other laboratory procedures for the identification of Hb variants in premarital diagnosis. On the other hand we discuss also the genetic origins of these Hb variants

First observation of Hb Tunis [beta124(H2)Pro>Ser] in Turkey.

Hb Tunis [beta124(H2)Pro>Ser] was reported from Tunisia in 1988. This hemoglobin variant was detected by isoelectric focusing moving just ahead of Hb A. It cannot be identified by standard hemoglobin electrophoresis due to its similar mobility to Hb A. It has normal stability and oxygen affinity and does not produce any clinical symptoms. Here, we report a heterozygous Hb Tunis [beta124(H2)Pro>Ser] case discovered for the first time in Turkey in a premarital screening program. This hemoglobin variant can be identified with high performance liquid chromatography analysis confirmed with DNA sequencing. We emphasize in our study the importance of an interdisciplinary collaborative study at the provincial basis for the success of the hemoglobinopathy control program

Preliminary virtual screening studies to identify grp78 inhibitors which may interfere with sars-cov-2 infection

SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Hypoglycaemic and anti-hyperglycaemic activity of Tabernanthe iboga aqueous extract in fructose-fed Streptozotocin type 2 diabetic rats

Publisher Copyright: © 2020, Institute of Korean Medicine, Kyung Hee University. This is a post-peer-review, pre-copyedit version of Bading-Taïka, B., Souza, A., Bourobou Bourobou, HP. et al. Hypoglycaemic and anti-hyperglycaemic activity of Tabernanthe iboga aqueous extract in fructose-fed streptozotocin type 2 diabetic rats. ADV TRADIT MED (ADTM) (2020). https://doi.org/10.1007/s13596-020-00484-0Root bark preparations of the Gabonese plant Tabernanthe iboga (T. iboga) has long been used in traditional medicine in Central and West African regions for the management of type 2 diabetes (T2D). This study is the first investigation of in vivo hypoglycaemic activity in healthy rats and anti-hyperglycaemic activity of T. iboga in a 10% fructose-fed (40 mg/kg i.p.) streptozotocin (STZ) injected type 2 diabetic rat model. T. iboga at 50 to 200 mg/kg induced hypoglycaemia activity over 3 h fasted glucose tolerance in healthy Wistar rats and anti-hyperglycaemic effects on non-fasted and fasted blood glucose in fructose-fed STZ T2D rats with no toxicity. Fructose-fed STZ T2D rats developed characteristic type 2 diabetic complications over 6 weeks exhibiting significantly elevated fasting and non-fasting blood glucose, polydipsia, reduced body weight gain and glucose and insulin tolerance compared with STZ alone and normal control rats. T. iboga (50 mg/kg and 200 mg/kg bw) administered p.o. once daily for 4 weeks significantly improved diabetic symptoms of polydipsia, reduced body weight, hyperglycaemia, glucose and insulin tolerance (as AUC) compared with fructose-fed STZ T2D rats. T. iboga aqueous extract (50 mg/kg and 200 mg/kg) also significantly reversed altered actions of marker enzymes of liver including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, HbA1c and elevated triglycerides in fructose-fed STZ type 2 diabetic rats. Our outcomes show that daily oral provision of T. iboga improves type 2 diabetes complications, superior to glibenclamide, in rat fructose-fed STZ model and offers the potential for safe clinical management of T2D in Gabon.Peer reviewe