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Distribution of transferrin (Tf) subtypes in several Mongoloid populations of East Asia

Saha N

Ann Hum Biol, 1987 7 1;14(4):349-56.
PMID: 3662433

The distribution of serum transferrin subtypes was determined by PAG electrophoresis and isoelectric focussing in a group of 2288 individuals from 10 Mongoloid populations of East Asia. The sample comprised 857 Chinese from different localities: Singapore (239), Malaysia (228), Taiwan (265), Hong Kong (65), Fouzhou (60); Koreans (332), Filipinos (281), Thais (455), Malays (335) and Indonesians (28). The frequencies of TfC1 varied from 0.73 to 0.79 in the Chinese and from 0.76 to 0.83 in the other Mongoloid populations. TfC3 was observed at a frequency of 0.02 in the Koreans and Chinese from Fouzhou. TfDChi was present in a low frequency (0.01 to 0.03) in all the populations. A low frequency of TfB was also present in all the populations. The phenotypic distribution of transferrin subtypes was at Hardy-Weinberg equilibrium in all the populations.

Matched MeSH terms: Transferrin/classification; Transferrin/genetics*; Transferrin/isolation & purification
HAPTOGLOBIN AND TRANSFERRIN STUDIES IN MALAYSIA

CHIN J

Med J Malaysia, 1964 Sep;19:71-2.
PMID: 14240067
Matched MeSH terms: Transferrin*
Haptoglobins, transferrins and serum gamma-globulin types in Malayan aborigines

Eng LI, Bolton JM, Fudenberg HH

Nature, 1967 Aug 12;215(5102):777.
PMID: 4168452
Matched MeSH terms: Transferrin*
Transferrin receptors-targeting nanocarriers for efficient targeted delivery and transcytosis of drugs into the brain tumors: a review of recent advancements and emerging trends

Choudhury H, Pandey M, Chin PX, Phang YL, Cheah JY, Ooi SC, et al.

Drug Deliv Transl Res, 2018 10;8(5):1545-1563.
PMID: 29916012 DOI: 10.1007/s13346-018-0552-2

Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood-brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs). However, overexpression of these TfRs on the GBM cell surface can also help to avoid restrictions of GBM cells to deliver chemotherapeutic agents within the tumor. Therefore, targeting of TfR-mediated delivery could counteract drug delivery issues in GBM and create a delivery system that could cross the BBB effectively to utilize ligand-conjugated drug complexes through receptor-mediated transcytosis. Hence, approach towards successful delivery of antitumor agents to the gliomas has been making possible through targeting these overexpressed TfRs within the CNS and glioma cells. This review article presents a thorough analysis of current understanding on Tf-conjugated nanocarriers as efficient drug delivery system.

Matched MeSH terms: Receptors, Transferrin/metabolism; Transferrin/metabolism*; Transferrin/chemistry
Tumor regression and modulation of gene expression via tumor-targeted tocotrienol niosomes

Tan DM, Fu JY, Wong FS, Er HM, Chen YS, Nesaretnam K

Nanomedicine (Lond), 2017 Oct;12(20):2487-2502.
PMID: 28972460 DOI: 10.2217/nnm-2017-0182

AIM: To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer.
MATERIALS & METHODS: Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy.
RESULTS: When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis.
CONCLUSION: Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.

Matched MeSH terms: Receptors, Transferrin/metabolism; Transferrin/administration & dosage; Transferrin/pharmacology*; Transferrin/chemistry*
Fulltext Phylogenetic analyses uncover a novel clade of transferrin in nonmammalian vertebrates

Mohd-Padil H, Mohd-Adnan A, Gabaldón T

Mol Biol Evol, 2013 Apr;30(4):894-905.
PMID: 23258311 DOI: 10.1093/molbev/mss325

Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups.

Matched MeSH terms: Transferrin/genetics*; Transferrin/chemistry
A longitudinal study of serum iron indices and haemoglobin concentration following copper-IUD insertion

Goh TH, Hariharan M, Tan CH

Contraception, 1980 Oct;22(4):389-95.
PMID: 7449387

The increase in menstrual blood loss associated with copper-bearing IUDs may cause or aggravate pre-existing anaemia. In order to evaluate this risk, 84 Malaysian women wearing copper-IUDs were studied longitudinally by means of serial measurements of blood haemoglobin concentration (Hb), serum iron (S/Fe) and transferrin saturation (T/S). The initial Hb was under 12 gm% in 33.7% of patients. The mean Hb showed no significant change up to 12 months while S/Fe fell significantly at the end of this time; the T/S was significantly reduced as early as 6 months post-insertion. There is a significant risk of anaemia following copper-IUD insertion, particularly with long-term usage. Progestogen-releasing IUDs may offer the most feasible solution to this problem in our local context since oral medication with iron or drugs to reduce menstrual blood loss is not practicable.

Matched MeSH terms: Transferrin
Utility of labile plasma iron and transferrin saturation in addition to serum ferritin as iron overload markers in different underlying anemias before and after deferasirox treatment

Porter JB, El-Alfy M, Viprakasit V, Giraudier S, Chan LL, Lai Y, et al.

Eur. J. Haematol., 2016 Jan;96(1):19-26.
PMID: 25691036 DOI: 10.1111/ejh.12540

Plasma markers in addition to serum ferritin (SF) may be useful for the assessment of iron overload; however, predictive utility may differ depending on underlying, transfusion-dependent, anemias.

Matched MeSH terms: Transferrin/metabolism*
Fulltext Qualitative flow cytometric analysis of Malaysian myelodysplastic syndromes (MDS) patients

Mohadese Hashem B, Ramasamy R, Sabariah MN, Seman Z

Med J Malaysia, 2012 Feb;67(1):77-80.
PMID: 22582553 MyJurnal

Myelodysplastic syndromes (MDS) are a group of haematological malignancies categorized by ineffective hematopoiesis that result in dysplasia. Although morphological diagnosis is a traditional and standard technique that is used for the diagnosis of MDS, the heterogeneous blood and bone marrow characteristics of MDS patients can potentially obscure the right diagnosis. Thus, we have utilized flow cytometric immunophenotyping as a supportive mechanism to obtain a more accurate and faster method for detection of abnormal markers in MDS. Flow cytometry was used for analyzing bone marrow samples from newly diagnosed MDS patients to investigate the abnormal antigen expression patterns in granulocytic, monocytic, erythroid, lymphoid lineages and myeloid precursors. The results were compared with those obtained from cases that had Idiopathic Thrombocytopenic Purpura (ITP) as a control. The most common abnormality found in the granulocytic lineage was the decrease of CD10. Low expressions of CD13 were the most frequent abnormality in the monocytic lineage. The erythroid lineage was found to have low expression of CD235A+/CD71+, reduce of CD71 and decreased CD235a. In conclusion, this method is useful for confirming cases in which it is difficult to make a diagnosis by morphology.

Matched MeSH terms: Receptors, Transferrin/analysis
RET-Y and RBC-Y in the diagnosis of iron deficiency associated with anaemia of inflammation

Jayaranee S, Sthaneshwar P

Int J Lab Hematol, 2010 Oct;32(5):512-8.
PMID: 20109166 DOI: 10.1111/j.1751-553X.2009.01215.x

We evaluated the usefulness of RET-Y and RBC-Y in distinguishing functional iron deficiency from iron-deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET-Y and RBC-Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC-Y and RET-Y values in iron-deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P < 0.001). The mean level of RET-Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET-Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC-Y. Receiver operating characteristic analysis also showed lower specificity for RBC-Y and RET-Y compared with that of sTfR and its log ferritin ratio (F-index). RET-Y and RBC-Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.

Matched MeSH terms: Receptors, Transferrin/blood
Use of red blood cell indices for the identification of iron deficiency among blood donors

Nadarajan V, Sthaneshwar P, Eow GI

Transfus Med, 2008 Jun;18(3):184-9.
PMID: 18598281 DOI: 10.1111/j.1365-3148.2008.00862.x

The objective of this study was to identify haematological parameters useful in screening for iron deficiency among blood donors. Iron deficiency is a common complication of blood donation and often goes unrecognized until anaemia develops. Biochemical markers such as soluble transferrin receptor (TfR), ferritin and log(TfR/F) have been proposed as more valid indicators of body iron status. Red blood cell (RBC) parameters are, however, more easily measured and have also been proposed as indicators of iron depletion. We measured ferritin and TfR in 192 blood donors together with RBC analysis, performed on two haematology analysers. Thirteen donors had parameters suggestive of haemoglobinopathy and were excluded from further analysis. Overall, 10% (18/179) of the remaining donors had iron deficiency, as defined by log(TfR/F) exceeding the 95th percentile of the value in the population of first-time donors. Using receiver operating characteristic analysis, the sensitivity of ferritin was 100%, with a specificity of 90% at a cut-off of 15 mug L(-1). The sensitivity and specificity of RBC-Y at a cut-off of 152 for detecting iron deficiency were 81 and 89%, respectively. Haemoglobin content of reticulocytes, meanwhile, showed sensitivity of 69% and specificity of 93% when a cut-off of 28 pg was used. Both measures compare favourably with haemoglobin which only showed a sensitivity of 50%, although specificity was 91% at a cut-off value of 125 g L(-1). The parameter RBC-Y can be useful as a screening measure for iron deficiency in blood donors.

Matched MeSH terms: Receptors, Transferrin/analysis
Biochemical genetic markers in the Kadazans of Sabah, Malaysia

Tan SG, Teng YS, Ganesan J, Lau KY, Lie-Injo LE

Hum Genet, 1979 Jul 18;49(3):349-53.
PMID: 289626

Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C5, group specific component, haptoglobin and transferrin. Kadazans were found to be polymorphic for GLO I, PGM I, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C5, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK.

Matched MeSH terms: Transferrin/genetics
Transferrin C subtyping in Malaysians and in Indonesians from North Sumatra

Tan SG, Gan YY, Asuan K

Hum Genet, 1982;60(4):369-70.
PMID: 7106773

Malays, Chinese, and Indians from Peninsular Malaysia; Ibans and Bidayuh from Sarawak State; Kadazans from Sabah State, Northern Borneo; and Bataks, Minangkabau, and Javanese from North Sumatra, Indonesia, were subtyped for transferrin C by polyacrylamide gel isoelectric focusing. All nine populations studied are polymorphic for two alleles, TfCl and TfC2, TfC3 was polymorphic in six populations and present as a rare variant in the other three. The frequency of TfC1 ranged from 0.855 in Bidayuh to 0.711 in Javanese, that of TfC2 from 0.231 in Indians to 0.113 in Bidayuh, and that of TfC3 from 0.030 in Javanese and Chinese to 0.008 in Bidayuh. TfDchi is polymorphic in all the populations that we studied except in Minangkabau, in whom it is present as a rare variant, and in Indians, in whom it is absent.

Matched MeSH terms: Transferrin/genetics*
Fulltext Reticulocyte haemoglobin as a biomarker for the detection of iron deficiency anaemia in haemodialysis patients on recombinant human erythropoietin

Jamian, E., Sanip, Z., Ramli, M., Mohd Daud, K., Mohamad, S., Hassan, R.

Journal of Biomedical and Clinical Sciences, 2018;3(2):29-34.
MyJurnal

Iron deficiency anaemia (IDA) frequently occurs in haemodialysis
(HD) patients undergoing recombinant human erythropoietin (rHuEPO)
therapy and is commonly associated with rHuEPO hypo-responsiveness.
However, the conventional iron indices are inadequate to exhibit the status or
utilisation of iron during erythropoiesis. The aim of this study was to elucidate
the accuracy and usefulness of the reticulocyte haemoglobin (RET-He) test
for diagnosing IDA in HD patients undergoing rHuEPO therapy. Methods: In
this cross-sectional study, fifty-five blood samples of HD patients on rHuEPO
therapy were collected and analysed for haematological and biochemical
parameters. A receiver operating characteristics curve was also plotted for
sensitivity and specificity analysis. IDA detection rates by RET-He, soluble
transferrin receptor (sTfR) and serum ferritin were 63.64%, 3.64% and 0%,
respectively. RET-He level was significantly correlated with sTfR level, mean
cell volume, mean cell haemoglobin level and the transferrin receptor-ferritin
index. The sensitivity and specificity of RET-He in detecting IDA were 78.3%
and 92.0%, respectively, with an area under the curve of 0.864. IDA was more
frequently detected by RET-He than by ferritin or sTfR in HD patients
undergoing rHuEPO therapy. The RET-He level also showed higher sensitivity
and specificity for the iron status in these patients. Therefore, RET-He is a
useful biomarker for the detection of IDA in HD patients undergoing rHuEPO
therapy.

Matched MeSH terms: Receptors, Transferrin; Transferrin
Haptoglobin, transferrin and serum albumin variants in the Dayaks of Sarawak

Ganesan J, Eng LI, Poon OB

Humangenetik, 1975 Oct 07;29(4):281-3.
PMID: 1176143

The Land Dayaks and the Sea Kayaks of Sarawak were surveyed for haptoglobin, transferrin and serum albumin variants. The Hp1 gene frequency was 0.385 in 283 Land Dayaks as well as in 205 Sea Kayaks. The TfDChi gene frequency in 283 Land Dayaks was 0.030 and in 188 Sea Kayaks it was 0.040. Serum albumin Medan was found in one of the 188 Sea Kayaks.

Matched MeSH terms: Transferrin/analysis*
Fulltext Serum soluble transferrin receptor in hypochromic microcytic anaemia

Jayaranee S, Sthaneshwar P

Singapore Med J, 2006 Feb;47(2):138-42.
PMID: 16435056

The objective of this study was to assess the clinical significance of soluble transferrin receptor (sTfR) in hypochromic microcytic anaemia.

Matched MeSH terms: Receptors, Transferrin/blood*
Improvement in the diagnostics of iron deficiency anemia using multiple marker combinations

Yang ES, Kim YS, Park CY, Kim JD, Song HJ

Sains Malaysiana, 2015;44:1653-1659.

Anemia of chronic disease (ACD) frequently occurred in patients with chronic inflammatory diseases and can be treated
by treating the underlying disease. On the other hand, iron-deficiency anemia (IDA), the most common type of anemia,
occurred with iron loss or when the iron requirement of the body was increased. Since the treatment methods for ACD
and IDA differ, it is important to clinically distinguish between the two types of anemia. In this study, we investigated and
evaluated the performance of a number of biomarkers, including ferritin, soluble transferrin receptor (sTfR), hepcidin,
C-reactive protein (CRP) and combination markers containing ferritin for the diagnosis of IDA using serum samples from
Korean patients (80 ACD and 48 IDA Korean patients). Among the single markers, ferritin exhibited the best performance
with 98.58% AUC and 97.50% sensitivity. In this study, a combination of two biomarkers was used to differentially
diagnose IDA and ACD. Among the combination markers, ferritin + sTfR showed the best performance with 99.51% AUC
and 98.75% sensitivity. We found that the ferritin + sTfR combination showed the best diagnostic performance with
1.25% higher SN than ferritin alone. Moreover, it also showed 10% better diagnostic performance than the single ferritin
marker within the data range where the distinction between ACD and IDA is unclear. We propose that using combination
markers containing ferritin may diagnose IDA more accurately and facilitate the determination of the appropriate anemia
treatment to expedite patient recovery.

Matched MeSH terms: Receptors, Transferrin
Fulltext Iron Chelation Properties of Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking

Md Nesran ZN, Shafie NH, Md Tohid SF, Norhaizan ME, Ismail A

Evid Based Complement Alternat Med, 2020;2020:7958041.
PMID: 32280356 DOI: 10.1155/2020/7958041

In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (-7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71; two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.

Matched MeSH terms: Receptors, Transferrin
Fulltext Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in assessment of anaemia in rheumatoid arthritis

Pavai S, Jayaranee S, Sargunan S

Med J Malaysia, 2007 Oct;62(4):303-7.
PMID: 18551934

Anaemia of chronic disease (ACD) is a frequent complication of rheumatoid arthritis (RA). A diagnostic difficulty in RA is the distinction between iron deficiency anaemia (IDA) and ACD. The aim of our study was to evaluate the usefulness of serum soluble transferrin receptor (sTfR) and sTfR/log ferritin (TfR-F) index to diagnose iron deficiency in RA patients with anaemia. Routine laboratory indices of anaemia and sTfR were measured in 20 healthy persons to form the control group, 30 patients with iron deficiency anaemia and 28 RA patients with anaemia. Serum sTfR levels were significantly elevated above the cut-off value in patients with IDA and those in the iron depleted RA subgroup (ferritin < 60 microg/L) compared with those in the control and iron repleted RA subgroup (ferritin > 60 microg/L). The same was observed for TfR-F index. However, five patients in the iron repleted RA sub group had an elevated sTfR level, of which two had increased TfR-F index. Serum sTfR correlated well with the markers of anaemia and not with ESR. Ferritin had no correlation with markers of anaemia but correlated well with ESR. Measurement of sTfR and TfR-F index are good indicators of iron deficiency in RA patients with anaemia. To be cost effective, sTfR can be estimated in RA patients with anaemia when the ferritin level is more than 60 microg/L.

Matched MeSH terms: Receptors, Transferrin*
Fulltext Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

Kosaisavee V, Suwanarusk R, Chua ACY, Kyle DE, Malleret B, Zhang R, et al.

Blood, 2017 09 14;130(11):1357-1363.
PMID: 28698207 DOI: 10.1182/blood-2017-02-764787

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi-infected human reticulocytes that are strikingly similar to those observed for P vivax These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.

Matched MeSH terms: Receptors, Transferrin/metabolism*

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