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Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings

Gane EJ, Charlton MR, Mohamed R, Sollano JD, Tun KS, Pham TTT, et al.

J Viral Hepat, 2020 05;27(5):466-475.
PMID: 31785182 DOI: 10.1111/jvh.13244

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

Matched MeSH terms: Hepatitis B e Antigens/blood
Evaluation of novel Parkinson's disease candidate genes in the Chinese population

Chew EGY, Liany H, Tan LCS, Au WL, Prakash KM, Annuar AA, et al.

Neurobiol Aging, 2019 02;74:235.e1-235.e4.
PMID: 30337193 DOI: 10.1016/j.neurobiolaging.2018.09.013

Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population.

Matched MeSH terms: Antigens, CD36/genetics*
Identification of a novel HLA-A*01 variant, HLA-A*01:211, in a Singaporean Malay bone marrow donor

Kaur A, Cho L, Cereb N, Lin PY, Yang KL

HLA, 2020 09;96(3):329-330.
PMID: 32227684 DOI: 10.1111/tan.13884

One nucleotide substitution in codon 73 of HLA-A*01:01:01:01 results in a novel allele, HLA-A*01:211.

Matched MeSH terms: HLA-A Antigens/genetics
Direct detection of Strongyloides infection via molecular and antigen detection methods

Balachandra D, Ahmad H, Arifin N, Noordin R

Eur J Clin Microbiol Infect Dis, 2021 Jan;40(1):27-37.
PMID: 32729057 DOI: 10.1007/s10096-020-03949-x

Laboratory diagnosis of Strongyloides infections can be grouped into direct and indirect detection methods, and a combination of the two methods is often needed to reach an accurate and timely diagnosis. This review focuses on non-conventional direct detection via molecular and antigen detection assays. Conventional PCR is the most commonly used molecular diagnostic for Strongyloides. Real-time PCR is accurate and highly sensitive for quantitative and qualitative analysis. Meanwhile, PCR-RFLP can efficiently distinguish human and dog isolates of S. stercoralis, S. fuelleborni (from monkey), and S. ratti (from rodent). Loop-mediated isothermal amplification (LAMP) amplifies DNA isothermally with high specificity, efficiency, and rapidity, and has potential for point-of-care (POC) translation. As for antigen detection assay, coproantigen detection ELISAs for strongyloidiasis traditionally relied on raising rabbit polyclonal antibodies against the parasite antigens for use as capture or detection reagents. Subsequently, hybridoma technology using animals has enabled the discovery of monoclonal antibodies specific to Strongyloides antigens and was utilised to develop antigen detection assays. In recent times, phage display technology has facilitated the discovery of scFv antibody against Strongyloides protein that can accelerate the development of such assays. Improvements in both direct detection methods are being made. Strongyloides molecular diagnostics is moving from the detection of a single infection to the simultaneous detection of soil-transmitted helminths. Meanwhile, antigen detection assays can also be multiplexed and aptamers can be used as antigen binders. In the near future, these two direct detection methods may be more widely used as diagnostic tools for strongyloidiasis.

Matched MeSH terms: Antigens, Helminth/immunology
Development of an immunochromatographic lateral flow dipstick for the detection of Mycobacterium tuberculosis 16 kDa antigen (Mtb-strip)

Mohd Amiruddin MN, Ang GY, Yu CY, Falero-Diaz G, Otero O, Reyes F, et al.

J Microbiol Methods, 2020 09;176:106003.
PMID: 32702386 DOI: 10.1016/j.mimet.2020.106003

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis (TB). This contagious disease remains a severe health problem in the world. The disease is transmitted via inhalation of airborne droplets carrying Mtb from TB patients. Early detection of the disease is vital to prevent transmission of the infection to people in close contact with the patients. To date, there is a need of a simple, rapid, sensitive and specific diagnostic test for TB. Previous studies showed the potential of Mtb 16 kDa antigen (Ag16) in TB diagnosis. In this study, lateral flow immunoassay, also called simple strip immunoassay or immunochromatographic test (ICT) for detection of Ag16 was developed (Mtb-strip) and assessed as a potential rapid TB diagnosis method. A monoclonal antibody against Ag16 was optimized as the capturing and detection antibody on the Mtb-strip. Parameters affecting the performance of the Mtb-strip were also optimized before a complete prototype was developed. Analytical sensitivity showed that Mtb-strip was capable to detect as low as 125 ng of purified Ag16. The analytical sensitivity of Mtb-strip suggests its potential usefulness in different clinical applications.

Matched MeSH terms: Antigens, Bacterial/immunology*
Extramedullary CD20-positive B-lymphoblastic lymphoma in a 5-year-old child: A diagnostic challenge

Abdul Jalil D, Raja Sabudin RZA, Tang YL, Masir N

Malays J Pathol, 2020 Aug;42(2):273-276.
PMID: 32860381

INTRODUCTION: Lymphoblastic leukaemia/lymphoma may present as an isolated extramedullary mass, which includes the musculoskeletal region involvement with normal or near-normal blood counts. The tumour may be in the form of B or T-lymphoblastic leukaemia/lymphoma. The clinical features and histological morphology of extramedullary B-lymphoblastic lymphoma (B-LBL) may mimic mature B-cell neoplasms, thus posing a diagnostic challenge. Arriving at the right diagnosis is crucial because these two diseases differ in their prognosis and management. A high index of suspicion is therefore important so as not to miss the correct diagnosis. The diagnosis may be overlooked because the clinical presentation may not be typical of B-LBL or the blood counts do not show any abnormalities. In this report, we highlight one such case where the diagnosis of B-LBL was missed because of its atypical presentation.

Matched MeSH terms: Antigens, CD/metabolism*
Distribution of immunoglobulin classes and IgG subclasses against a culture filtrate antigen of Burkholderia pseudomallei in melioidosis patients

Chenthamarakshan V, Kumutha MV, Vadivelu J, Puthucheary SD

J Med Microbiol, 2001 Jan;50(1):55-61.
PMID: 11192506 DOI: 10.1099/0022-1317-50-1-55

The class and subclass distribution of antibody response to the culture filtrate antigen (CFA) of Burkholderia pseudomallei was examined in the sera of 45 septicaemic and 17 localised melioidosis cases and 40 cases clinically suspected of melioidosis and the results were compared with those from high-risk and healthy control groups. The geometric mean titre index (GMTI) values for all classes and subclasses of immunoglobulins examined were higher for sera from the proven and clinically suspected melioidosis cases than for the control groups. However, the highest response in the three patient groups was that of IgG with GMTIs ranging from 219.4 to 291.6 and the lowest was for IgM with GMTIs of 22.5, 24.3 and 28.7. The IgA response was intermediate with GMTIs ranging from 119.2 to 170. The GMTIs were highest for IgG in septicaemic and localised infections and for IgA and IgM in localised infections. As regards IgG subclass distribution, IgG1 and IgG2 were the predominant subclasses produced against the CFA in contrast to IgG3 and IgG4, which were produced in low amounts. None of the sera from the control groups had any significant titres of antibodies.

Matched MeSH terms: Antigens, Bacterial/immunology*
Fulltext Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

Kalaw E, Lim M, Kutasovic JR, Sokolova A, Taege L, Johnstone K, et al.

Br J Cancer, 2020 11;123(11):1665-1672.
PMID: 32939056 DOI: 10.1038/s41416-020-01065-3

BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.
METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.
RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P

Matched MeSH terms: Antigens, CD274/biosynthesis*
Fulltext Determination of the specificities of monoclonal and polyclonal antibodies to Neospora, Toxoplasma and Cryptosporidium by fluorescent antibody test (FAT)

Latif BM, Jakubek EB

Trop Biomed, 2008 Dec;25(3):225-31.
PMID: 19287361

Flourescent antibody test (FAT) was applied to determine the cross-reactivities of monoclonal (mAb), polyclonal (pAb) antibodies to Neospora, Toxoplasma and Cryptosporidium and antisera from cattle naturally infected with Neospora canium against antigens from a number of sources. Both mAb and pAb to Neospora reacted strongly (FAT titre up to 2560) with the homologous antigens and demonstrated weak titre (80) or no reaction with both Toxoplasma and Cryptosporidium antigens. Also mAb and pAb to Toxoplasma gondii reacted at titres of 80 - 640 with homologous antigens and at titres of 10-40 with N. caninum. No cross-reactions with either mAb or pAb antibodies to N. caninum and T. gondii were observed with Cryptosporidium parvum. The same results were observed with C. parvum mAb when tested with both N. caninum and T. gondii antigens. Sera from cattle naturally infected with N. caninum had titres ranging from 80- 640 with N. caninum antigens, and 10- 40 with T. gondii and C. parvum antigens. At low dilutions, the complete surfaces of Neospora and Toxoplasma parasites were fluorescent, while in higher dilutions only dotted fluorescence appeared on the apical complex. These results indicated the presence of cross-reactivity between Neospora and Toxoplasma but not with Cryptosporidium. Accordingly the recommended cut-off antibody titre for diagnosis of neosporosis is 80.

Matched MeSH terms: Antigens, Protozoan/immunology*
Fulltext Characterisation of a truncated Toxoplasma gondii surface antigen 2 (SAG2) secreted by the methylotrophic yeast Pichia pastoris

Lau YL, Shamilah H, Fong MY

Trop Biomed, 2006 Dec;23(2):186-93.
PMID: 17322821 MyJurnal

A truncated form of surface antigen 2 (SAG2) of the protozoan parasite Toxoplasma gondii was cloned and expressed in the methylotrophic yeast Pichia pastoris. This recombinant antigen, designated as recSAG2-N, contained only the N-terminal half of the native SAG2. The recSAG2-N was secreted by the Pichia pastoris into the culture supernatant, and it was harvested by using the trichloroacetic acid precipitation method. Specificity of recSAG2-N was evaluated in western blot assays. Fifty human serum samples, including 32 from confirmed cases of toxoplasmosis, were tested. Results from the assays showed that recSAG2-N reacted with sera from the toxoplasmosis cases only. In vivo experiments showed that serum from mice which received recSAG2-N reacted with the native SAG2 of T. gondii.

Matched MeSH terms: Antigens, Protozoan/metabolism*
Identification and characterization of Leishmania amastigote and axenic form antigens

Abdelhaleem AA, Elamin EM, Bakheit SM, Mukhtar MM

Trop Biomed, 2019 Dec 01;36(4):866-873.
PMID: 33597459

This study was aimed to identify and characterize Leishmania amastigote, and axenic form antigens. Two in vitro techniques were used to change leishmania parasite isolates from promastigote form to amastigotes and amastigote like (axenic) forms. The main strategy relied upon in vitro infection of murine macrophages cell line J774 with leishmania promastigote, at 37°C with 5% CO2, while the second technique relied upon the culture of promastigote at 37°C with low pH (5.5), and 5-10% CO2. Proteins were extracted and fractionated utilizing 12% Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS PAGE). Antigens were recognized using both immune dot blot and western blot procedures. PCR was performed for recognition of leishmania parasites in infected J774 macrophages. L. major was quicker in infectivity of macrophages cell line than L. donovani. Shared proteins ranging from 26-116 kDa were identified by SDS PAGE in all stages. Immune Dot-blot method showed positive outcomes, while western blot identified an exceptional antigen band of 16 kDa in amastigote, this unique band could be of value in diagnosis and vaccination of leishmaniasis. PCR results confirmed presence of both isolates demonstrating that coinfection is conceivable, and no indications of hereditary recombination at kinetoplast DNA (kDNA) were identified in macrophages simultaneously infected by L. major and L. donovani.

Matched MeSH terms: Antigens, Protozoan/analysis*
Time trends of chronic HBV infection over prior decades - A global analysis

Ott JJ, Horn J, Krause G, Mikolajczyk RT

J Hepatol, 2017 Jan;66(1):48-54.
PMID: 27592304 DOI: 10.1016/j.jhep.2016.08.013

BACKGROUND & AIMS: Information on trends in chronic hepatitis B virus (HBV) prevalence across countries is lacking. We studied changes in chronic HBV infection over previous decades by country, and assessed patterns of change between and within WHO-defined regions.
METHODS: Based on data from a published systematic review on chronic HBV, we applied a linear model on the logit scale to assess time trends in country-specific prevalence. Estimated HBsAg prevalence in 2000 and relative changes in prevalence over time were evaluated by country and region.
RESULTS: Sufficient data were available for 50 countries, mostly showing reductions in prevalence over time. Various degrees of heterogeneity were observed within regions, with a relatively homogenous pattern in the Eastern Mediterranean region with strong decreases in HBsAg prevalence. Europe showed a mixed pattern: higher and stable chronic HBsAg prevalence in Eastern, and constantly low prevalence in Western Europe. In Africa, some countries demonstrated no change in prevalence; increases were seen in Uganda (odds ratio 1.05 per year; 95% confidence interval 1.04-1.06), Nigeria (1.02; 1.02-1.02), Senegal (1.01; 1.01-1.02), and South Africa (1.02; 1.01-1.02). With some exceptions, country-patterns overlapped among countries of South East Asian and Western Pacific regions, characterized by low-medium HBsAg decreases, most prominent in China and Malaysia.
CONCLUSIONS: Most countries experienced decreases in HBsAg prevalence. Dynamics varied, even within regions; decreases occurred mostly before the direct effects of childhood vaccination may have manifested. These findings together with stable and increasing HBsAg prevalence in some countries of Africa and Eastern Europe indicate the need for further tailored country-specific prevention.
LAY SUMMARY: This study investigated time trends in prevalence of chronic HBV infection in 50 countries worldwide over the last decade, by estimating relative changes in prevalence. Results show decreases in chronic HBV infection in most countries; no changes or increases in prevalence are noted in some African countries. Reasons for time changes need to be investigated further; based on the results, various prevention measures have contributed to reductions, and further tailored HBV prevention is required to combat the disease on a global level.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
FAS c.-671A>G polymorphism and cervical cancer risk: a case-control study and meta-analysis

Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R

Cancer Genet, 2017 02;211:18-25.
PMID: 28279307 DOI: 10.1016/j.cancergen.2017.01.004

This study aimed to investigate the association between FAS c.-671A>G polymorphism and cervical cancer risk in a case-control setting, followed by a meta-analysis of the published literatures. The case-control study involved genotyping of the polymorphism in 185 histopathologically confirmed cervical cancer patients and 209 cancer-free female controls utilizing PCR-RFLP technique, followed by logistic regression analyses. Meta-analysis was then conducted under homozygous, heterozygous, dominant, recessive and allele contrast models to combine data from 12 studies which consisted of 2798 cases and 3039 controls. Our case-control analysis revealed a significant association of the variant allele (G) and the homozygous variant genotype (GG) of the FAS polymorphism with an increased risk of cervical cancer. Subgroup analysis by ethnicity further confirmed the risk association in Malays (P 0.05). However, results of meta-analysis suggested a lack of association between the polymorphism and cervical cancer risk in all the five genetic models analyzed. In conclusion, while the FAS c.-671A>G polymorphism may serve as a biomarker for cervical cancer risk prediction among the Malays, there is a limited usability of the polymorphism as a cervical cancer risk biomarker in other populations.

Matched MeSH terms: Antigens, CD95/genetics*
Importance of extended blood group genotyping in multiply transfused patients

Osman NH, Sathar J, Leong CF, Zulkifli NF, Raja Sabudin RZA, Othman A, et al.

Transfus Apher Sci, 2017 Jun;56(3):410-416.
PMID: 28438419 DOI: 10.1016/j.transci.2017.03.009

Blood group antigen systems are not limited to the ABO blood groups. There is increasing interest in the detection of extended blood group systems on the red cell surface. The conventional method used to determine extended blood group antigens or red cell phenotype is by serological testing, which is based on the detection of visible haemagglutination or the presence of haemolysis. However, this technique has many limitations due to recent exposure to donor red cell, certain drugs or medications or other diseases that may alter the red cell membrane. We aimed to determine the red cell blood group genotype by SNP real time PCR and to compare the results with the conventional serological methods in multiply transfused patients. Sixty-three patients participated in this study whose peripheral blood was collected and blood group phenotype was determined by serological tube method while the genotype was performed using TaqMan®Single Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood group systems. Discrepancies were found between the phenotype and genotype results for all blood groups tested. Accurate red blood cell antigen profiling is important for patients requiring multiple transfusions. The SNP RT-PCR platform is a reliable alternative to the conventional method.

Matched MeSH terms: Blood Group Antigens/genetics*
HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi

Sumithran E, Prathap K

Cancer, 1977 Oct;40(4):1618-20.
PMID: 198100

Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.

Matched MeSH terms: Hepatitis B Antigens*
Immunogenetic aspects of nasopharyngeal carcinoma. V. Confirmation of a Chinese-related HLA profile (A2, Singapore 2) associated with an increased risk in Chinese for nasopharyngeal carcinoma

Simons MJ, Wee GB, Singh D, Dharmalingham S, Yong NK, Chau JC, et al.

Natl Cancer Inst Monogr, 1977 Dec;47:147-51.
PMID: 613233

Histocompatibility locus A typing of 43 Malaysian Chinese and 51 Hong Kong Chinese patients with nasopharyngeal carcinoma (NPC) confirmed the association between the occurrence of A2-Sin 2 and the increased risk for NPC that was previously demonstrated in Singapore Chinese. The results support the previous interpretation that the histocompatibility locus A genotype of importance in NPC predisposition is the A2-Sin 2 haplotype. The histocompatibility locus A-linked, genetically determined NPC risk is common to Asian Chinese from at least three geographic locations.

Matched MeSH terms: HLA Antigens*
Histocompatibility leukocyte antigen patterns and nasopharyngeal carcinoma

Simons MJ, Day NE

Natl Cancer Inst Monogr, 1977 Dec;47:143-6.
PMID: 613232

Incidence patterns indicated the prominent role of genetic factors in this type of cancer. A histocompatibility leukocyte antigen (HLA) profile of A2 and B-locus antigen, Singapore 2 (Sin 2), was identified. An association between these genes and increased risk for nasopharyngeal carcinoma (NPC), was confirmed. The risk was restricted to the "co-occurrence" of A2, B-Sin 2, suggesting that the genotype predisposing to the development of NPC was the A, B-Sin 2 haplotype. Similar associations were found to exist in Malaysian and Hong Kong Chinese so the A2, B-Sin 2 phenotype is a feature common to Asian Chinese in at least three locations. Preliminary HLA studies of medium NPC incidence in Tunisians and Malays indicated that patients with NPC of both ethnic types have altered HLA antigen profiles. If the findings of a locus-B antigen deficit in Tunisians and the role of A9 with B-locus antigens in Malays can be confirmed and clarified, the histocompatibility genetic hypothesis of NPC predisposition would be substantially strengthened.

Matched MeSH terms: HLA Antigens*
Antibodies to EBV related antigens in West Malaysian children

Tan DS, Henle G

Med J Malaya, 1972 Sep;27(1):27-9.
PMID: 4345645
Matched MeSH terms: Antigens, Viral*
Fulltext Genetic and population studies of the blood types and serum factors among Indians and Chinese from Malaya

Steinberg AG, Lai LYC, Vos GH, Singh RB, Lim TW

Am J Hum Genet, 1961 Dec;13:355-71.
PMID: 13916666

The ABO, MN and Rh blood types, and the Hp, Tf, and Gm [Gm (a), Gm (x), Gm(b), and Gm-like] factors were determined for 128 unrelated Indians (parents of families, 63 with two parents tested and two with one parent tested), and 90 unrelated Chinese (parents of 46 families, 44 with two parents tested and two with one parent tested), and for the offspring from these families. The frequencies of the several blood types are presented. They were done primarily to aid in paternity testing. They compare favorably with the findings of previous studies. The allele Hp1 is rare in the Indian population (.09) and relatively infrequent in the Chinese (.29). Unfortunately, the data shed no light on the problem of the inheritance of the phenotype Hp O. Only Tf C was found among the Indians. About four per cent of the Chinese were heterozygous for Tf CD,, all other were Tf CC. The Indians have a high frequency of Gm(a) and of Gm (x), and a low frequency of Gm (b). They appear to have alleles Gma, Gmax, and Gmb in the following frequencies: .535, .234(5), and .230(5), respectively. Three families appear to have a GMxb allele, providing the offspring are not extra-marital. The Chinese appear to have the alleles Gm^ab, Gm^a, and Gm^ax in the following frequencies: .741, .231, and .028, respectively.

Matched MeSH terms: Blood Group Antigens/genetics*
Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: fabrication, characterization, and cellular and molecular evidences of enhanced bone regeneration

Dong J, Tao L, Abourehab MAS, Hussain Z

Int J Biol Macromol, 2018 Sep;116:1268-1281.
PMID: 29782984 DOI: 10.1016/j.ijbiomac.2018.05.116

Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis.

Matched MeSH terms: Antigens, Differentiation/biosynthesis

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