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Fulltext Organotypic slice culture based on in ovo electroporation for chicken embryonic central nervous system

Yang C, Li X, Li S, Chai X, Guan L, Qiao L, et al.

J Cell Mol Med, 2019 03;23(3):1813-1826.
PMID: 30565384 DOI: 10.1111/jcmm.14080

Organotypic slice culture is a living cell research technique which blends features of both in vivo and in vitro techniques. While organotypic brain slice culture techniques have been well established in rodents, there are few reports on the study of organotypic slice culture, especially of the central nervous system (CNS), in chicken embryos. We established a combined in ovo electroporation and organotypic slice culture method to study exogenous genes functions in the CNS during chicken embryo development. We performed in ovo electroporation in the spinal cord or optic tectum prior to slice culture. When embryonic development reached a specific stage, green fluorescent protein (GFP)-positive embryos were selected and fluorescent expression sites were cut under stereo fluorescence microscopy. Selected tissues were embedded in 4% agar. Tissues were sectioned on a vibratory microtome and 300 μm thick sections were mounted on a membrane of millicell cell culture insert. The insert was placed in a 30-mm culture dish and 1 ml of slice culture media was added. We show that during serum-free medium culture, the slice loses its original structure and propensity to be strictly regulated, which are the characteristics of the CNS. However, after adding serum, the histological structure of cultured-tissue slices was able to be well maintained and neuronal axons were significantly longer than that those of serum-free medium cultured-tissue slices. As the structure of a complete single neuron can be observed from a slice culture, this is a suitable way of studying single neuronal dynamics. As such, we present an effective method to study axon formation and migration of single neurons in vitro.

Matched MeSH terms: Nerve Tissue Proteins/metabolism*; Green Fluorescent Proteins/metabolism*
Fulltext Reductive evolution in outer membrane protein biogenesis has not compromised cell surface complexity in Helicobacter pylori

Webb CT, Chandrapala D, Oslan SN, Bamert RS, Grinter RD, Dunstan RA, et al.

Microbiologyopen, 2017 12;6(6).
PMID: 29055967 DOI: 10.1002/mbo3.513

Helicobacter pylori is a gram-negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host-pathogen interactions mediated by Helicobacter-specific proteins in the bacterial outer membrane. These outer membrane proteins (OMPs) are anchored to the cell surface via a C-terminal β-barrel domain, which requires their assembly by the β-barrel assembly machinery (BAM). Here we have assessed the complexity of the OMP C-terminal β-barrel domains employed by H. pylori, and characterized the H. pyloriBAM complex. Around 50 Helicobacter-specific OMPs were assessed with predictive structural algorithms. The data suggest that H. pylori utilizes a unique β-barrel architecture that might constitute H. pylori-specific Type V secretions system. The structural and functional diversity in these proteins is encompassed by their extramembrane domains. Bioinformatic and biochemical characterization suggests that the low β-barrel-complexity requires only minimalist assembly machinery. The H. pylori proteins BamA and BamD associate to form a BAM complex, with features of BamA enabling an oligomerization that might represent a mechanism by which a minimalist BAM complex forms a larger, sophisticated machinery capable of servicing the outer membrane proteome of H. pylori.

Matched MeSH terms: Bacterial Outer Membrane Proteins/genetics; Bacterial Outer Membrane Proteins/metabolism; Bacterial Outer Membrane Proteins/chemistry*
Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus

Teh LS, Lee MK, Wang F, Manivasagar M, Charles PJ, Nicholson GD, et al.

Br J Rheumatol, 1993 Aug;32(8):663-5.
PMID: 8348266

We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.

Matched MeSH terms: Ribosomal Proteins/immunology*; Protozoan Proteins*
Fulltext Chaos-embedded particle swarm optimization approach for protein-ligand docking and virtual screening

Tai HK, Jusoh SA, Siu SWI

J Cheminform, 2018 Dec 14;10(1):62.
PMID: 30552524 DOI: 10.1186/s13321-018-0320-9

BACKGROUND: Protein-ligand docking programs are routinely used in structure-based drug design to find the optimal binding pose of a ligand in the protein's active site. These programs are also used to identify potential drug candidates by ranking large sets of compounds. As more accurate and efficient docking programs are always desirable, constant efforts focus on developing better docking algorithms or improving the scoring function. Recently, chaotic maps have emerged as a promising approach to improve the search behavior of optimization algorithms in terms of search diversity and convergence speed. However, their effectiveness on docking applications has not been explored. Herein, we integrated five popular chaotic maps-logistic, Singer, sinusoidal, tent, and Zaslavskii maps-into PSOVina[Formula: see text], a recent variant of the popular AutoDock Vina program with enhanced global and local search capabilities, and evaluated their performances in ligand pose prediction and virtual screening using four docking benchmark datasets and two virtual screening datasets.
RESULTS: Pose prediction experiments indicate that chaos-embedded algorithms outperform AutoDock Vina and PSOVina in ligand pose RMSD, success rate, and run time. In virtual screening experiments, Singer map-embedded PSOVina[Formula: see text] achieved a very significant five- to sixfold speedup with comparable screening performances to AutoDock Vina in terms of area under the receiver operating characteristic curve and enrichment factor. Therefore, our results suggest that chaos-embedded PSOVina methods might be a better option than AutoDock Vina for docking and virtual screening tasks. The success of chaotic maps in protein-ligand docking reveals their potential for improving optimization algorithms in other search problems, such as protein structure prediction and folding. The Singer map-embedded PSOVina[Formula: see text] which is named PSOVina-2.0 and all testing datasets are publicly available on https://cbbio.cis.umac.mo/software/psovina .

Matched MeSH terms: Proteins
Effect of pH and Salt Concentration on Protein Solubility of slaughtered and non-slaughtered broiler chicken meat

Mst Kamrun Nahar, Uda Hashim, Zarina Zakaria, Md Fazlul Bari

Sains Malaysiana, 2017;46:719-724.

This study examined the influence of pH and salt concentration on the protein solubility of slaughtered and non-slaughtered broiler chicken meat. Three types of salt (NaCl, Na2SO4, and (NH4)2SO4), five different pH levels (5.0, 6.0, 7.0, 8.0 and 9.0) and five salt concentrations (0.4, 0.8, 1.2, 1.6, and 2.0 M) were examined. Each type of salt showed distinctive activities for slaughtered and non-slaughtered meat protein solubility. Soluble protein concentration increased as pH increased (p<0.05) from pH5.0 to 8.0 and decreased from pH8.0 to 9.0. It was also observed that protein solubility increased as the salt concentration increased. Protein solubility significantly increased (p<0.05) in the non-slaughtered meat compared to the slaughtered meat at pH8.0 for Na2SO4 at 1.2 M.

Matched MeSH terms: Proteins
Improvement of colloidal stability in colloidal processing for highly translucent, nanosized zirconia

Chuin HC, Che Husna Azhari, Mohamed Aboras, Masfueh Razali, Andanastuti Muchtar

Sains Malaysiana, 2018;47:1591-1597.

This study aimed to improve the colloidal stability of yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP)
suspension through colloidal processing to obtain highly translucent Y-TZP. Agglomeration is often the main complication
in the processing of nanosized Y-TZP as it deteriorates mechanical and optical properties. Thus, colloidal processing
is necessary to mitigate the agglomeration in Y-TZP. The colloidal stability of Y-TZP suspension plays a key role for the
success of colloidal processing. In this study, colloidal processing was conducted at several stages, namely, dispersant
addition, pH adjustment and sedimentation. Changes in particle size and zeta potential at various stages were recorded.
The suspensions were then slip-casted to form green bodies. Green bodies were sintered and characterized for density
and translucency. The results showed that dispersant addition followed by pH adjustment effectively dispersed soft
agglomerates by introducing electrosteric stabilization, whereas sedimentation successfully segregated hard agglomerates
and contributed excellent colloidal stability. With high colloidal stability, the translucency of Y-TZP was improved by
approximately 30%. This study demonstrated different colloidal processing stages and proved that high colloidal stability
and fine particle size are vital to produce highly translucent Y-TZP.

Matched MeSH terms: Intracellular Signaling Peptides and Proteins
Fulltext Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.

Molecules, 2020 Jul 28;25(15).
PMID: 32731323 DOI: 10.3390/molecules25153403

Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.

Matched MeSH terms: Neoplasm Proteins/metabolism; Zebrafish Proteins/metabolism
Novel cross-linked enzyme aggregates of levanase from Bacillus lehensis G1 for short-chain fructooligosaccharides synthesis: Developmental, physicochemical, kinetic and thermodynamic properties

Abd Rahman NH, Jaafar NR, Abdul Murad AM, Abu Bakar FD, Shamsul Annuar NA, Md Illias R

Int J Biol Macromol, 2020 Sep 15;159:577-589.
PMID: 32380107 DOI: 10.1016/j.ijbiomac.2020.04.262

Short-chain fructooligosaccharides (scFOSs) can be produced from the levan hydrolysis using levanase. Levanase from Bacillus lehensis G1 (rlevblg1) is an enzyme that specifically converts levan to scFOSs. However, the use of free levanase presents a lack of stability and reusability, thus hindering the synthesis of scFOSs for continuous reactions. Here, CLEAs for rlevblg1 were prepared and characterized. Cross-linked levanase aggregates using glutaraldehyde (CLLAs-ga) and bovine albumin serum (CLLAs-ga-bsa) showed the best activity recovery of 92.8% and 121.2%, respectively. The optimum temperature of CLLAs-ga and CLLAs-ga-bsa was increased to 35 °C and 40 °C, respectively, from its free rlevblg1 (30 °C). At high temperature (50 °C), the half-life of CLLAs-ga-bsa was higher than that of free rlevblg1 and CLLAs-ga. Both CLLAs exhibited higher stability at pH 9 and pH 10. Hyperactivation of CLLAs-ga-bsa was achieved with an effectiveness factor of more than 1 and with improved catalytic efficiency. After 3 h reaction, CLLAs-ga-bsa produced the highest total scFOSs yield of 35.4% and total sugar of 60.4% per gram levan. Finally, the reusability of CLLAs for 8 cycles with more than 50% activity retained makes them as a potential synthetic catalyst to be explored for scFOSs synthesis.

Matched MeSH terms: Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/chemistry
Site-saturation mutagenesis of mutant L-asparaginase II signal peptide hydrophobic region for improved excretion of cyclodextrin glucanotransferase

Ismail A, Illias RM

J Ind Microbiol Biotechnol, 2017 Dec;44(12):1627-1641.
PMID: 28921081 DOI: 10.1007/s10295-017-1980-6

The excretion of cyclodextrin glucanotransferase (CGTase) into the culture medium offers significant advantages over cytoplasmic expression. However, the limitation of Escherichia coli is its inability to excrete high amount of CGTase outside the cells. In this study, modification of the hydrophobic region of the N1R3 signal peptide using site-saturation mutagenesis improved the excretion of CGTase. Signal peptide mutants designated M9F, V10L and A15Y enhanced the excretion of CGTase three-fold and demonstrated two-fold higher secretion rate than the wild type. However, high secretion rate of these mutants was non-productive for recombinant protein production because it caused up to a seven-fold increase in cell death compared to the wild type. Our results indicated that the excretion of CGTase is highly dependent on hydrophobicity, secondary conformation and the type and position of amino acids at the region boundary and core segment of the h-region.

Matched MeSH terms: Recombinant Proteins/biosynthesis; Recombinant Proteins/genetics; Recombinant Proteins/secretion
LAT is essential for the mast cell stabilising effect of tHGA in IgE-mediated mast cell activation

Tan JW, Israf DA, Md Hashim NF, Cheah YK, Harith HH, Shaari K, et al.

Biochem Pharmacol, 2017 Nov 15;144:132-148.
PMID: 28813645 DOI: 10.1016/j.bcp.2017.08.010

Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells. However, the mechanism of action (MOA) as well as the molecular target underlying the mast cell stabilising effect of tHGA has not been previously investigated. In this study, DNP-IgE-sensitised RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA. To dissect the MOA of tHGA in IgE-mediated mast cell activation, the effect of tHGA on the transcription of IL-4 and TNF-α mRNA was determined using Real Time-Polymerase Chain Reaction (qPCR) followed by Calcium Influx Assay to confirm the involvement of calcium in the activation of mast cells. The protein lysates were analysed by using Western Blot to determine the effect of tHGA on various important signalling molecules in the LAT-PLCγ-MAPK and PI3K-NFκB pathways. In order to identify the molecular target of tHGA in IgE-mediated mast cell activation, the LAT and LAT2 genes in RBL-2H3 cells were knocked-down by using RNA interference to establish a LAT/LAT2 competition model. The results showed that tHGA inhibited the transcription of IL-4 and TNF-α as a result of the suppression of calcium influx in activated RBL-2H3 cells. The results from Western Blot revealed that tHGA primarily inhibited the LAT-PLCγ-MAPK pathway with partial inhibition on the PI3K-p65 pathway without affecting Syk. The results from RNAi further demonstrated that tHGA failed to inhibit the release of mediators associated with mast cell degranulation under the LAT/LAT2 competition model in the absence of LAT. Collectively, this study concluded that the molecular target of tHGA could be LAT and may provide a basis for the development of a mast cell stabiliser which targets LAT.

Matched MeSH terms: Membrane Proteins/metabolism*; Adaptor Proteins, Signal Transducing/metabolism*
Fulltext A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation

Chear CT, Nallusamy R, Canna SW, Chan KC, Baharin MF, Hishamshah M, et al.

Clin Immunol, 2020 02;211:108328.
PMID: 31870725 DOI: 10.1016/j.clim.2019.108328

Autoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A > T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations.

Matched MeSH terms: Calcium-Binding Proteins/genetics*; CARD Signaling Adaptor Proteins/genetics*
The requirements for sterol regulatory element-binding protein (Srebp) and stimulatory protein 1 (Sp1)-binding elements in the transcriptional activation of two freshwater fish Channa striata and Danio rerio elovl5 elongase

Goh PT, Kuah MK, Chew YS, Teh HY, Shu-Chien AC

Fish Physiol Biochem, 2020 Aug;46(4):1349-1359.
PMID: 32239337 DOI: 10.1007/s10695-020-00793-w

Fish are a major source of beneficial n-3 LC-PUFA in human diet, and there is considerable interest to elucidate the mechanism and regulatory aspects of LC-PUFA biosynthesis in farmed species. Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis involves the activities of two groups of enzymes, the fatty acyl desaturase (Fads) and elongase of very long-chain fatty acid (Elovl). The promoters of elovl5 elongase, which catalyses the rate-limiting reaction of elongating polyunsaturated fatty acid (PUFA), have been previously described and characterized from several marine and diadromous teleost species. We report here the cloning and characterization of elovl5 promoter from two freshwater fish species, the carnivorous snakehead fish (Channa striata) and zebrafish. Results show the presence of sterol-responsive elements (SRE) in the core regulatory region of both promoters, suggesting the importance of sterol regulatory element-binding protein (Srebp) in the regulation of elovl5 for both species. Mutagenesis luciferase and electrophoretic mobility shift assays further validate the role of SRE for basal transcriptional activation. In addition, several Sp1-binding sites located in close proximity with SRE were present in the snakehead promoter, with one having a potential synergy with SRE in the regulation of elovl5 expression. The core zebrafish elovl5 promoter fragment also directed in vivo expression in the yolk syncytial layer of developing zebrafish embryos.

Matched MeSH terms: Zebrafish Proteins/physiology*; Sterol Regulatory Element Binding Proteins/physiology*
Potential application of Leishmania tarentolae as an alternative platform for antibody expression

Lai JY, Klatt S, Lim TS

Crit Rev Biotechnol, 2019 May;39(3):380-394.
PMID: 30720351 DOI: 10.1080/07388551.2019.1566206

Through the discovery of monoclonal antibody (mAb) technology, profound successes in medical treatment against a wide range of diseases have been achieved. This has led antibodies to emerge as a new class of biodrugs. As the "rising star" in the pharmaceutical market, extensive research and development in antibody production has been carried out in various expression systems including bacteria, insects, plants, yeasts, and mammalian cell lines. The major benefit of eukaryotic expression systems is the ability to carry out posttranslational modifications of the antibody. Glycosylation of therapeutic antibodies is one of these important modifications, due to its influence on antibody structure, stability, serum half-life, and complement recruitment. In recent years, the protozoan parasite Leishmania tarentolae has been introduced as a new eukaryotic expression system. L. tarentolae is rich in glycoproteins with oligosaccharide structures that are very similar to humans. Therefore, it is touted as a potential alternative to mammalian expression systems for therapeutic antibody production. Here, we present a comparative review on the features of the L. tarentolae expression system with other expression platforms such as bacteria, insect cells, yeasts, transgenic plants, and mammalian cells with a focus on mAb production.

Matched MeSH terms: Recombinant Proteins/biosynthesis*; Recombinant Proteins/immunology; Recombinant Proteins/therapeutic use
ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM

Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
PMID: 31030477

Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
[CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).

Matched MeSH terms: Membrane Proteins/metabolism*; ADAM Proteins/metabolism*
Innate immune function of serine/threonine-protein kinase from Macrobrachium rosenbergii in response to host-pathogen interactions

Ravichandran G, Pasupuleti M, Arasu MV, Al-Dhabi NA, Arshad A, Arockiaraj J

Fish Shellfish Immunol, 2020 Nov;106:332-340.
PMID: 32758637 DOI: 10.1016/j.fsi.2020.07.068

The occurrences of multiple drug-resistant strains have been relentlessly increasing in recent years. The aquaculture industry has encountered major disease outbreaks and crucially affected by this situation. The usage of non-specific chemicals and antibiotics expedites the stimulation of resistant strains. Triggering the natural defense mechanism would provide an effective and safest way of protecting the host system. Hence, we have investigated the innate immune function of serine/threonine-protein kinase (STPK) in Macrobrachium rosenbergii (Mr). The in-silico protein analysis resulted in the identification of cationic antimicrobial peptide, MrSL-19, with interesting properties from STPK of M. rosenbergii. Antimicrobial assay, FACS and SEM analysis demonstrated that the peptide potentially inhibits Staphylococcus aureus by interacting with its membrane. The toxic study on MrSL-19 demonstrated that the peptide is not toxic against HEK293 cells as well as human erythrocytes. This investigation showed the significant innate immune property of an efficient cationic antimicrobial peptide, MrSL-19 of STPK from M. rosenbergii.

Matched MeSH terms: Arthropod Proteins/genetics; Arthropod Proteins/immunology; Arthropod Proteins/chemistry
Generation of a T cell receptor (TCR)-like single domain antibody (sDAb) against a Mycobacterium Tuberculosis (Mtb) heat shock protein (HSP) 16kDa antigen presented by Human Leukocyte Antigen (HLA)-A*02

Dass SA, Norazmi MN, Dominguez AA, Miguel MESGS, Tye GJ

Mol Immunol, 2018 09;101:189-196.
PMID: 30007228 DOI: 10.1016/j.molimm.2018.07.001

The discovery of heat shock protein 16 kDa antigen protein has deepen the understanding of latent tuberculosis since it was found to be primarily expressed by Mycobacterium tuberculosis during latent phase leading to the rapid optimization and development in terms of diagnosis and therapeutics. Recently, T cell receptor-like antibody has been explored extensively targeting various diseases due to its dual functionality (T cell receptor and antibody). In this study, a TCR-like domain antibody (A2/Ab) with the binding capacity to Mtb heat shock protein (HSP) 16 kDa antigen presented by major histocompatible complex (MHC) HLA-A*02 was successfully generated via biopanning against human domain antibody library. The generated antibody (A2/Ab) exhibited strong functionality and binding capacity against the target assuring the findings of this study to be beneficial for the development of latent tuberculosis diagnosis and immunotherapeutics in future.

Matched MeSH terms: Heat-Shock Proteins
Fulltext Two Genetically Distinct Plasmodium knowlesi Duffy Binding Protein Alpha Region II (PkDBPαII) Haplotypes Demonstrate Higher Binding Level to Fy(a+b+) Erythrocytes than Fy(a+b--) Erythrocytes

Liew CC, Lau YL, Fong MY, Cheong FW

Am J Trop Med Hyg, 2020 05;102(5):1068-1071.
PMID: 32189613 DOI: 10.4269/ajtmh.19-0836

Invasion of human erythrocytes by merozoites of Plasmodium knowlesi involves interaction between the P. knowlesi Duffy binding protein alpha region II (PkDBPαII) and Duffy antigen receptor for chemokines (DARCs) on the erythrocytes. Information is scarce on the binding level of PkDBPαII to different Duffy antigens, Fya and Fyb. This study aims to measure the binding level of two genetically distinct PkDBPαII haplotypes to Fy(a+b-) and Fy(a+b+) human erythrocytes using erythrocyte-binding assay. The binding level of PkDBPαII of Peninsular Malaysian and Malaysian Borneon haplotypes to erythrocytes was determined by counting the number of rosettes formed in the assay. Overall, the Peninsular Malaysian haplotype displayed higher binding activity than the Malaysian Borneon haplotype. Both haplotypes exhibit the same preference to Fy(a+b+) compared with Fy(a+b-), hence justifying the vital role of Fyb in the binding to PkDBPαII. Further studies are needed to investigate the P. knowlesi susceptibility on individuals with different Duffy blood groups.

Matched MeSH terms: Protozoan Proteins/genetics*; Protozoan Proteins/immunology; Protozoan Proteins/metabolism
New monoclinic form of {O-Ethyl N-(4-nitro-phen-yl)thio-carbamato-κS}(tri-4-tolyl-phosphane-κP)gold(I): crystal structure and Hirshfeld surface analysis

Kuan FS, Jotani MM, Tiekink ERT

Acta Crystallogr E Crystallogr Commun, 2017 Oct 01;73(Pt 10):1465-1471.
PMID: 29250359 DOI: 10.1107/S2056989017012865

The title phosphanegold(I) thiol-ate compound, [Au(C9H9N2O3S)(C21H21P)], is a second monoclinic polymorph (space group P21/c) that complements a previously reported Cc polymorph [Broker & Tiekink (2008 ▸). Acta Cryst. E64, m1582]. An SP donor set defines an approximately linear geometry about the gold atom in both forms. The key distinguishing feature between the present structure and the previously reported polymorph rests with the relative disposition of the thiol-ate ligand. In the title compound, the orientation is such to place the oxygen atom in close contact with the gold atom [Au⋯O = 2.915 (2) Å], in contrast to the aryl ring in the original polymorph. In the crystal, linear supra-molecular chains along the a-axis direction mediated by C-H⋯π and nitro-O⋯π inter-actions are found. These pack with no directional inter-actions between them. The analysis of the Hirshfeld surfaces for both forms of [Au(C9H9N3O3S)(C21H21P)] indicates quite distinctive inter-action profiles relating to the differences in inter-molecular contacts found in their respective crystals.

Matched MeSH terms: Complement System Proteins
Periodontal management in a primary polycythemia rubra vera patient: A case report

Hassan FW, Mohd N

Spec Care Dentist, 2021 Jan;41(1):92-97.
PMID: 33125720 DOI: 10.1111/scd.12537

BACKGROUND/AIM: Polycythemia rubra vera (PRV) is a myeloproliferative disease, which is characterized by the proliferation of all three major hematopoietic groups (erythrocytes, leucocytes and platelets). This hematological condition presented with different clinical manifestations depending on the thrombohemorrhagic status of the patient. It is suggested patient with preexisting PRV may suffer complication during periodontal treatment. Thus, this case would therefore demonstrate periodontal management outcome in PRV patient.
CASE PRESENTATION: A 60-year-old Malay gentleman presented to the Periodontic Clinic, Universiti Kebangsaan Malaysia. He was a known case of primary PRV for the past 5 years. Intraoral examination showed generalized periodontal deep pockets ranging from 5 to 10 mm. He was diagnosed as Stage III Grade C periodontitis. Nonsurgical periodontal therapy was provided, followed by surgical correction of residual periodontal deep pockets on teeth 17, 11, and 23. He was reviewed at 4-month intervals for supportive periodontal therapy after stabilization of his periodontal condition.
CONCLUSION: Polycythemia rubra vera (PRV) patients should have preoperative therapeutic control for more than 4 months and have been treated with myelosuppressive agents prior to periodontal surgery. Good oral hygiene and periodical supportive periodontal therapy are the key factors for successful periodontal treatment outcomes in well-controlled PRV patients.

Matched MeSH terms: GPI-Linked Proteins
Effect of soy protein on the small bowel mucosa of young infants recovering from acute gastroenteritis

Iyngkaran N, Yadav M, Looi LM, Boey CG, Lam KL, Balabaskaran S, et al.

J Pediatr Gastroenterol Nutr, 1988 Jan-Feb;7(1):68-75.
PMID: 3335989

The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Vegetable Proteins/adverse effects; Vegetable Proteins/pharmacology*; Soybean Proteins

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