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  1. Protein and peptide delivery to lungs by using advanced targeted drug delivery
    Chellappan DK, Prasher P, Saravanan V, Vern Yee VS, Wen Chi WC, Wong JW, et al.
    Chem Biol Interact, 2022 Jan 05;351:109706.
    PMID: 34662570 DOI: 10.1016/j.cbi.2021.109706
    The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.
    Matched MeSH terms: Proteins/administration & dosage*; Proteins/therapeutic use
  2. Immediately early 2 (IE-2) and DNA polymerase SiRNA as virus-specific antiviral against novel transplacental cytomegalovirus strain ALL-03 in vitro
    Balakrishnan KN, Abdullah AA, Bala JA, Jesse FFA, Abdullah CAC, Noordin MM, et al.
    Infect Genet Evol, 2021 06;90:104783.
    PMID: 33640483 DOI: 10.1016/j.meegid.2021.104783
    OBJECTIVE: This study investigated the suitability of siRNA targeting specific genes that cause inhibition of virus replication in vitro especially for the virus that capable of crossing placenta and we employed a novel transplacental rat cytomegalovirus that mimics infection in human.

    METHODS: Six unique siRNAs with three each targeting different regions of IE2 (ie2a, ie2b and ie2c) and DNA polymerase (dpa, dpb and dpc) were prepared and tested for antiviral activities. The efficacy as an antiviral was determined in in-vitro by measuring TCID50 virus titer, severity of virus-induced cytopathic effect (CPE), intracellular viral genome loads by droplet digital PCR, the degree of apoptosis in siRNA-treated cells and relative expression of viral mRNA in infected Rat Embryo Fibroblast (REF) cells.

    FINDINGS: Remarkably, the siRNAs: dpa, dpb and IE2b, significantly reduced virus yield (approximately >90%) compared to control group at day 18 post infection (p.i). Changes in CPE indicated that DNA polymerase siRNAs were capable of protecting cells against CMV infection at day 14 p.i with higher efficiency than GCV (at the concentration of 300 pmol). Gene expression analysis revealed a marked down regulation of the targeted DNA polymerase gene (73.9%, 96.0% and 90.7% for dpa, dpb and dpc siRNA, respectively) and IE2 gene (50.8%, 49.9% and 15.8% for ie2a, ie2b and ie2c siRNA, respectively) when measured by RT-qPCR. Intracellular viral DNA loads showed a significant reduction for all the DNA polymerase siRNAs (dpa: 96%, dpb: 98% and dpc:92) compared to control group (P 

    Matched MeSH terms: Immediate-Early Proteins/genetics; Immediate-Early Proteins/pharmacology*
  3. Clinicopathologic and immunohistochemical differences in complete and partial hydatidiform moles in a multiracial Malaysian population
    Hayati AR, Tan GC
    Int J Gynecol Pathol, 2005 Jul;24(3):277-85.
    PMID: 15968205
    Matched MeSH terms: Nuclear Proteins/biosynthesis*; Nuclear Proteins/immunology
  4. From discovery to spread: The evolution and phylogeny of Getah virus
    Li YY, Liu H, Fu SH, Li XL, Guo XF, Li MH, et al.
    Infect Genet Evol, 2017 11;55:48-55.
    PMID: 28827175 DOI: 10.1016/j.meegid.2017.08.016
    Getah virus (GETV) was first isolated in Malaysia in 1955. Since then, epidemics in horses and pigs caused by GETV have resulted in huge economic losses. At present, GETV has spread across Eurasia and Southeast Asia, including mainland China, Korea, Japan, Mongolia, and Russia. Data show that the Most Recent Common Ancestor (MRCA) of GETV existed about 145years ago (95% HPD: 75-244) and gradually evolved into four distinct evolutionary populations: Groups I-IV. The MRCA of GETVs in Group III, which includes all GETVs isolated from mosquitoes, pigs, horses, and other animals since the 1960s (from latitude 19°N to 60°N), existed about 51years ago (95% HPD: 51-72). Group III is responsible for most viral epidemics among domestic animals. An analysis of the GETV E2 protein sequence and structure revealed seven common amino acid mutation sites. These sites are responsible for the structural and electrostatic differences detected between widespread Group III isolates and the prototype strain MM2021. These differences may account for the recent geographical radiation of the virus. Considering the economic significance of GETV infection in pigs and horses, we recommend the implementation of strict viral screening and monitoring programs.
    Matched MeSH terms: Viral Proteins/genetics; Viral Proteins/chemistry
  5. Isolation by culture and PCR identification of LipL32 gene of pathogenic Leptospira spp. in wild rats of Kuala Lumpur
    Latifah I, Abdul Halim A, Rahmat MS, Nadia MF, Ubil ZE, Asmah H, et al.
    Malays J Pathol, 2017 08;39(2):161-166.
    PMID: 28866698 MyJurnal
    BACKGROUND: A study was conducted to confirm the status of rats as the carrier of pathogenic leptospira in Kuala Lumpur, Malaysia.

    METHOD: A total of 140 urine samples were collected from trapped rats. These samples were cultured in EMJH enriched media and 18 of these samples (12.9%) were found to be positive when observed under x40 by dark field microscope. Genomic DNA was extracted from all the 18 native isolates for PCR.

    RESULT: All the 18 isolates generated the expected 786 base pair band when the set of primers known to amplify LipL32 gene were utilized. These results showed that the primers were suitable to be used for the identification of pathogenic leptospira from the 18 rat samples.

    CONCLUSION: The sequencing of the PCR products and BLAST analysis performed on each representative isolates confirmed the pathogenic status of all these native isolates as the LipL32 gene was detected in all the Leptospira isolates. This indicates that the rats are carriers of the pathogenic leptospira in the study area, and therefore are of public health importance.

    Matched MeSH terms: Bacterial Outer Membrane Proteins/genetics*; Bacterial Outer Membrane Proteins/isolation & purification
  6. Metabolic Effect of Dietary Taurine Supplementation on Nile Tilapia (Oreochromis nilotictus) Evaluated by NMR-Based Metabolomics
    Shen G, Huang Y, Dong J, Wang X, Cheng KK, Feng J, et al.
    J Agric Food Chem, 2018 Jan 10;66(1):368-377.
    PMID: 29215281 DOI: 10.1021/acs.jafc.7b03182
    Taurine is indispensable in aquatic diets that are based solely on plant protein, and it promotes growth of many fish species. However, the physiological and metabolome effects of taurine on fish have not been well described. In this study, 1H NMR-based metabolomics approaches were applied to investigate the metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to visualize the metabolic trajectory and reveal the possible mechanisms of metabolic effects of dietary taurine supplementation on tilapia growth. After extraction using aqueous and organic solvents, 19 taurine-induced metabolic changes were evaluated in our study. The metabolic changes were characterized by differences in carbohydrate, amino acid, lipid, and nucleotide contents. The results indicate that taurine supplementation could significantly regulate the physiological state of fish and promote growth and development. These results provide a basis for understanding the mechanism of dietary taurine supplementation in fish feeding. 1H NMR spectroscopy, coupled with multivariate pattern recognition technologies, is an efficient and useful tool to map the fish metabolome and identify metabolic responses to different dietary nutrients in aquaculture.
    Matched MeSH terms: Fish Proteins/metabolism; Fish Proteins/chemistry
  7. Gene isolation using degenerate primers targeting protein motif: A laboratory exercise
    Yeo BPH, Foong LC, Tam SM, Lee V, Hwang SS
    Biochem Mol Biol Educ, 2018 01;46(1):47-53.
    PMID: 29131478 DOI: 10.1002/bmb.21089
    Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the isolation and characterization of many plant resistance gene analogues (RGAs), is featured in the development of a series of laboratory experiments using important molecular biology techniques. A set of previously isolated RGA sequences is used as the model for performing sequence alignment and visualising 3D protein structure using current bioinformatics programs (Clustal Omega and Argusdock software). A pair of established degenerate primer sequences is provided for the prediction of targeted amino acids sequences in the RGAs. Reverse transcription-polymerase chain reaction (RT-PCR) is used to amplify RGAs from total RNA samples extracted from the tropical wild relative of black pepper, Piper colubrinum (Piperaceae). This laboratory exercise enables students to correlate specific DNA sequences with respective amino acid codes and the interaction between conserved motifs of resistance genes with putatively targeted proteins. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):47-53, 2018.
    Matched MeSH terms: Proteins/genetics*; Proteins/chemistry
  8. Characterization of Eleusine indica with gene mutation or amplification in EPSPS to glyphosate
    Chen J, Jiang C, Huang H, Wei S, Huang Z, Wang H, et al.
    Pestic Biochem Physiol, 2017 Nov;143:201-206.
    PMID: 29183593 DOI: 10.1016/j.pestbp.2017.09.012
    The evolution of weed-resistant species threatens the sustainable use of glyphosate, which is the most important herbicide widely used in agriculture worldwide. Moreover, the high glyphosate resistance (>180-fold based on LD50) of Eleusine indica found in Malaysia, which carries a double mutation in its 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), made the control of this species more difficult. By contrast, the same species carrying the same double mutation in EPSPS (T102I+P106S) but found in China only shows a resistance level of not more than 14-fold based on GR50. The resistance level of this population is four times higher than that of the population carrying a single mutation (P106L). Although the members of this population survive under a high glyphosate dosage of 10,080gaeha-1, their growth was significantly inhibited by glyphosate under the recommend dose (840gaeha-1), where in the fresh weight was 85.4% of the control. EPSPS expression, relative copy number, and EPSPS activity in this population were similar to those of the susceptible population. In addition, the expression of two glutathione transferase (GST) genes (GST-U8 and GST-23) and the enzyme activity of the GST in this population did not significantly differ from those of the susceptible population. This finding is important in elucidating the resistance of the naturally evolved glyphosate-resistant (GR) weed species carrying a double mutation in EPSPS to glyphosate.
    Matched MeSH terms: Plant Proteins/genetics; Plant Proteins/metabolism
  9. Fulltext Outer membrane proteins analysis of Shigella sonnei and evaluation of their antigenicity in Shigella infected individuals
    Harikrishnan H, Banga Singh KK, Ismail A
    PLoS One, 2017;12(8):e0182878.
    PMID: 28846684 DOI: 10.1371/journal.pone.0182878
    Bacillary dysentery caused by infection with Shigella spp. remains as serious and common health problem throughout the world. It is a highly multi drug resistant organism and rarely identified from the patient at the early stage of infection. S. sonnei is the most frequently isolated species causing shigellosis in industrialized countries. The antigenicity of outer membrane protein of this pathogen expressed during human infection has not been identified to date. We have studied the antigenic outer membrane proteins expressed by S. sonnei, with the aim of identifying presence of specific IgA and IgG in human serum against the candidate protein biomarkers. Three antigenic OMPs sized 33.3, 43.8 and 100.3 kDa were uniquely recognized by IgA and IgG from patients with S. sonnei infection, and did not cross-react with sera from patients with other types of infection. The antigenic proteome data generated in this study are a first for OMPs of S. sonnei, and they provide important insights of human immune responses. Furthermore, numerous prime candidate proteins were identified which will aid the development of new diagnostic tools for the detection of S. sonnei.
    Matched MeSH terms: Bacterial Outer Membrane Proteins/immunology*; Bacterial Outer Membrane Proteins/metabolism
  10. Humanization of chimeric anti-CD20 antibody by logical and bioinformatics approach with retention of biological activity
    Khoo YL, Cheah SH, Chong H
    Immunotherapy, 2017 06;9(7):567-577.
    PMID: 28595518 DOI: 10.2217/imt-2017-0016
    AIM: To develop a fully bioactive humanized antibody from the chimeric rituximab for potential clinical applications using a relatively simpler and faster logical and bioinformatics approach.

    METHODS: From bioinformatics data, mismatched mouse amino acids in variable light and heavy chain amphipathic regions were identified and substituted with those common to human antibody framework. Appropriate synthetic DNA sequences inserted into vectors were transfected into HEK293 cells to produce the humanized antibody.

    RESULTS: Humanized antibodies showed specific binding to CD20 and greater cytotoxicity to cancer WIL2-NS cell proliferation than rituximab in vitro.

    CONCLUSION: A humanized version of rituximab with potential to be developed into a biobetter for treatment of B-cell disorders has been successfully generated using a logical and bioinformatics approach.

    Matched MeSH terms: Recombinant Fusion Proteins/genetics*; Recombinant Fusion Proteins/metabolism
  11. Fulltext AidP, a novel N-Acyl homoserine lactonase gene from Antarctic Planococcus sp
    See-Too WS, Ee R, Lim YL, Convey P, Pearce DA, Yin WF, et al.
    Sci Rep, 2017 02 22;7:42968.
    PMID: 28225085 DOI: 10.1038/srep42968
    Planococcus is a Gram-positive halotolerant bacterial genus in the phylum Firmicutes, commonly found in various habitats in Antarctica. Quorum quenching (QQ) is the disruption of bacterial cell-to-cell communication (known as quorum sensing), which has previously been described in mesophilic bacteria. This study demonstrated the QQ activity of a psychrotolerant strain, Planococcus versutus strain L10.15T, isolated from a soil sample obtained near an elephant seal wallow in Antarctica. Whole genome analysis of this bacterial strain revealed the presence of an N-acyl homoserine lactonase, an enzyme that hydrolyzes the ester bond of the homoserine lactone of N-acyl homoserine lactone (AHLs). Heterologous gene expression in E. coli confirmed its functions for hydrolysis of AHLs, and the gene was designated as aidP (autoinducer degrading gene from Planococcus sp.). The low temperature activity of this enzyme suggested that it is a novel and uncharacterized class of AHL lactonase. This study is the first report on QQ activity of bacteria isolated from the polar regions.
    Matched MeSH terms: Bacterial Proteins/classification; Bacterial Proteins/genetics*
  12. Fulltext A novel sequence-based predictor for identifying and characterizing thermophilic proteins using estimated propensity scores of dipeptides
    Charoenkwan P, Chotpatiwetchkul W, Lee VS, Nantasenamat C, Shoombuatong W
    Sci Rep, 2021 Dec 10;11(1):23782.
    PMID: 34893688 DOI: 10.1038/s41598-021-03293-w
    Owing to their ability to maintain a thermodynamically stable fold at extremely high temperatures, thermophilic proteins (TTPs) play a critical role in basic research and a variety of applications in the food industry. As a result, the development of computation models for rapidly and accurately identifying novel TTPs from a large number of uncharacterized protein sequences is desirable. In spite of existing computational models that have already been developed for characterizing thermophilic proteins, their performance and interpretability remain unsatisfactory. We present a novel sequence-based thermophilic protein predictor, termed SCMTPP, for improving model predictability and interpretability. First, an up-to-date and high-quality dataset consisting of 1853 TPPs and 3233 non-TPPs was compiled from published literature. Second, the SCMTPP predictor was created by combining the scoring card method (SCM) with estimated propensity scores of g-gap dipeptides. Benchmarking experiments revealed that SCMTPP had a cross-validation accuracy of 0.883, which was comparable to that of a support vector machine-based predictor (0.906-0.910) and 2-17% higher than that of commonly used machine learning models. Furthermore, SCMTPP outperformed the state-of-the-art approach (ThermoPred) on the independent test dataset, with accuracy and MCC of 0.865 and 0.731, respectively. Finally, the SCMTPP-derived propensity scores were used to elucidate the critical physicochemical properties for protein thermostability enhancement. In terms of interpretability and generalizability, comparative results showed that SCMTPP was effective for identifying and characterizing TPPs. We had implemented the proposed predictor as a user-friendly online web server at http://pmlabstack.pythonanywhere.com/SCMTPP in order to allow easy access to the model. SCMTPP is expected to be a powerful tool for facilitating community-wide efforts to identify TPPs on a large scale and guiding experimental characterization of TPPs.
    Matched MeSH terms: Heat-Shock Proteins/metabolism; Heat-Shock Proteins/chemistry*
  13. Fulltext The Marine Natural Product Manzamine A Inhibits Cervical Cancer by Targeting the SIX1 Protein
    Karan D, Dubey S, Pirisi L, Nagel A, Pina I, Choo YM, et al.
    J Nat Prod, 2020 Feb 28;83(2):286-295.
    PMID: 32022559 DOI: 10.1021/acs.jnatprod.9b00577
    Natural products remain an important source of drug leads covering unique chemical space and providing significant therapeutic value for the control of cancer and infectious diseases resistant to current drugs. Here, we determined the antiproliferative activity of a natural product manzamine A (1) from an Indo-Pacific sponge following various in vitro cellular assays targeting cervical cancer (C33A, HeLa, SiHa, and CaSki). Our data demonstrated the antiproliferative effects of 1 at relatively low and non-cytotoxic concentrations (up to 4 μM). Mechanistic investigations confirmed that 1 blocked cell cycle progression in SiHa and CaSki cells at G1/S phase and regulated cell cycle-related genes, including restoration of p21 and p53 expression. In apoptotic assays, HeLa cells showed the highest sensitivity to 1 as compared to other cell types (C33A, SiHa, and CaSki). Interestingly, 1 decreased the levels of the oncoprotein SIX1, which is associated with oncogenesis in cervical cancer. To further investigate the structure-activity relationship among manzamine A (1) class with potential antiproliferative activity, molecular networking facilitated the efficient identification, dereplication, and assignment of structures from the manzamine class and revealed the significant potential in the design of optimized molecules for the treatment of cervical cancer. These data suggest that this sponge-derived natural product class warrants further attention regarding the design and development of novel manzamine analogues, which may be efficacious for preventive and therapeutic treatment of cancer. Additionally, this study reveals the significance of protecting fragile marine ecosystems from climate change-induced loss of species diversity.
    Matched MeSH terms: Homeodomain Proteins/metabolism*; Homeodomain Proteins/chemistry
  14. Establishment of a Nipah virus rescue system
    Yoneda M, Guillaume V, Ikeda F, Sakuma Y, Sato H, Wild TF, et al.
    Proc Natl Acad Sci U S A, 2006 Oct 31;103(44):16508-13.
    PMID: 17053073
    Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in an outbreak of infection in pigs and humans and incurred a high fatality rate in humans. Fruit bats, living in vast areas extending from India to the western Pacific, were identified as the natural reservoir of the virus. However, the mechanisms that resulted in severe pathogenicity in humans (up to 70% mortality) and that enabled crossing the species barrier were not known. In this study, we established a system that enabled the rescue of replicating NiVs from a cloned DNA by cotransfection of a constructed full-length cDNA clone and supporting plasmids coding virus nucleoprotein, phosphoprotein, and polymerase with the infection of the recombinant vaccinia virus, MVAGKT7, expressing T7 RNA polymerase. The rescued NiV (rNiV), by using the newly developed reverse genetics system, showed properties in vitro that were similar to the parent virus and retained the severe pathogenicity in a previously established animal model by experimental infection. A recombinant NiV was also developed, expressing enhanced green fluorescent protein (rNiV-EGFP). Using the virus, permissibility of NiV was compared with the presence of a known cellular receptor, ephrin B2, in a number of cell lines of different origins. Interestingly, two cell lines expressing ephrin B2 were not susceptible for rNiV-EGFP, indicating that additional factors are clearly required for full NiV replication. The reverse genetics for NiV will provide a powerful tool for the analysis of the molecular mechanisms of pathogenicity and cross-species infection.
    Matched MeSH terms: Recombinant Proteins/genetics; Recombinant Proteins/metabolism
  15. Fulltext Habenular kisspeptin modulates fear in the zebrafish
    Ogawa S, Nathan FM, Parhar IS
    Proc Natl Acad Sci U S A, 2014 Mar 11;111(10):3841-6.
    PMID: 24567386 DOI: 10.1073/pnas.1314184111
    Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the control of reproduction in vertebrates. We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are located in the habenula, which project to the median raphe. kiss2 neurons are located in the hypothalamic nucleus and send axonal projections to gonadotropin-releasing hormone neurons and regulate reproductive functions. However, the physiological significance of the Kiss1 expressed in the habenula remains unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)-induced fear response in the zebrafish. We found that AS-evoked fear experience significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed transcript 1 and solute carrier family 6, member 4) in the zebrafish. Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons. The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear response. These findings provide an insight into the role of the habenular kisspeptin system in inhibiting fear.
    Matched MeSH terms: Ribosome Inactivating Proteins, Type 1/metabolism; Ribosome Inactivating Proteins, Type 1/pharmacology
  16. RNA-sequencing exploration on SIR2 and SOD genes in Polyalthia longifolia leaf methanolic extracts (PLME) mediated anti-aging effects in Saccharomyces cerevisiae BY611 yeast cells
    Hemagirri M, Chen Y, Gopinath SCB, Adnan M, Patel M, Sasidharan S
    Biogerontology, 2024 Aug;25(4):705-737.
    PMID: 38619670 DOI: 10.1007/s10522-024-10104-y
    Polyalthia longifolia is well-known for its abundance of polyphenol content and traditional medicinal uses. Previous research has demonstrated that the methanolic extract of P. longifolia leaves (PLME, 1 mg/mL) possesses anti-aging properties in Saccharomyces cerevisiae BY611 yeast cells. Building on these findings, this study delves deeper into the potential antiaging mechanism of PLME, by analyzing the transcriptional responses of BY611 cells treated with PLME using RNA-sequencing (RNA-seq) technology. The RNA-seq analysis results identified 1691 significantly (padj 
    Matched MeSH terms: Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism
  17. Silencing E6/E7 Oncoproteins in SiHa Cells Treated with siRNAs and Oroxylum indicum Extracts Induced Apoptosis by Upregulating p53/pRb Pathways
    Sisin NNT, Kong AR, Edinur HA, Jamil NIN, Che Mat NF
    Appl Biochem Biotechnol, 2024 Jul;196(7):4234-4255.
    PMID: 37922032 DOI: 10.1007/s12010-023-04762-w
    E6 and E7 human papillomavirus (HPV) oncoproteins play a significant role in the malignant transformation of infected cervical cancer cells via suppression of tumour suppressor pathways by targeting p53 and pRb, respectively. This study aimed to investigate the anticancer effects of Oroxylum indicum (OI) leaves' methanol extract on SiHa cervical cancer cells. Expression of apoptosis-related proteins (Bcl-2, caspase (cas)-3, and cas-9), viral oncoproteins (E6 and E7), and tumour suppressor proteins (p53 and pRb) were evaluated using western blot analysis before and after E6/E7 small interfering RNAs (siRNAs) transfection. In addition, the E6/E7 mRNA expression levels were assessed with real-time (RT)-PCR. The present study showed that the OI extract effectively hindered the proliferation of SiHa cells and instigated increments of cas-3 and cas-9 expressions but decreased the Bcl-2 expressions. The OI extract inhibited E6/E7 viral oncoproteins, leading to upregulation of p53 and pRb tumour suppressor genes in SiHa cells. Additionally, combinatorial treatment of OI extract and gossypin flavonoid induced restorations of p53 and pRb. Treatment with OI extract in siRNA-transfected cells also further suppressed E6/E7 expression levels and further upregulations of p53 and pRb proteins. In conclusion, OI extract treatment on siRNAs-transfected SiHa cells can additively and effectively block E6- and E7-dependent p53 and pRb degradations. All these data suggest that OI could be explored for its chemotherapeutic potential in cervical cancer cells with HPV-integrated genomes.
    Matched MeSH terms: Papillomavirus E7 Proteins/genetics; Papillomavirus E7 Proteins/metabolism
  18. Fulltext Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions
    Loh SY, Jahans-Price T, Greenwood MP, Greenwood M, Hoe SZ, Konopacka A, et al.
    eNeuro, 2017;4(6).
    PMID: 29279858 DOI: 10.1523/ENEURO.0243-17.2017
    The supraoptic nucleus (SON) is a group of neurons in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised graphical lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions. The most active nodal gene identified within the network was Caprin2. Caprin2 encodes an RNA-binding protein that we have previously shown to be vital for the functioning of osmoregulatory neuroendocrine neurons in the SON of the rat hypothalamus. To test the validity of the Glasso network, we either overexpressed or knocked down Caprin2 transcripts in differentiated rat pheochromocytoma PC12 cells and showed that these manipulations had significant opposite effects on the levels of putative target mRNAs. These studies suggest that the predicative power of the Glasso algorithm within an in vivo system is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.
    Matched MeSH terms: RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism*
  19. Fulltext Effects of Seasonal Variability on the Physicochemical, Biochemical, and Nutritional Composition of Western Peninsular Malaysia Gracilaria manilaensis
    Aroyehun AQ, Palaniveloo K, Ghazali F, Rizman-Idid M, Abdul Razak S
    Molecules, 2019 Sep 10;24(18).
    PMID: 31510066 DOI: 10.3390/molecules24183298
    This study evaluated the effect of seasonal variation on the physicochemical, biochemical, and nutritional composition of Gracilaria manilaensis. Sampling was designed during the main monsoon seasons in Malaysia-the Southwest monsoon (SWM) and Northeast monsoon (NEM)-to understand the intraspecific variation (p < 0.05). Carbohydrates, protein, and dietary fiber were found to be higher in NEM-G. manilaensis, whereas a higher ash content was quantified in SWM-G. manilaensis. No significant differences were found in crude lipid and moisture content (p > 0.05). Vitamin B2 was calculated as (0.29 ± 0.06 mg 100 g-1) and (0.38 ± 0.06 mg 100 g-1) for the NEM and SWM samples, respectively (p < 0.05). The fatty acid profile showed the dominance of saturated fatty acids (SFAs)-palmitic acids, stearic acid, and myristic acid-while the mineral contents were found to be good sources of calcium (1750.97-4047.74 mg 100 g-1) and iron (1512.55-1346.05 mg 100 g-1). Tryptophan and lysine were recorded as the limiting essential amino acids (EAAs) in NEM G. manilaensis, while leucine and phenylalanine were found to be the limiting EAAs in the SWM samples. None of the extracts exhibited antibacterial properties against the screened strains. The study concluded that seasonal changes have a great effect on the biochemical composition of G. manilaensis.
    Matched MeSH terms: Proteins/isolation & purification; Proteins/chemistry
  20. Fulltext Response of Cellular Innate Immunity to Cnidarian Pore-Forming Toxins
    Yap WY, Hwang JS
    Molecules, 2018 Oct 04;23(10).
    PMID: 30287801 DOI: 10.3390/molecules23102537
    A group of stable, water-soluble and membrane-bound proteins constitute the pore forming toxins (PFTs) in cnidarians. They interact with membranes to physically alter the membrane structure and permeability, resulting in the formation of pores. These lesions on the plasma membrane causes an imbalance of cellular ionic gradients, resulting in swelling of the cell and eventually its rupture. Of all cnidarian PFTs, actinoporins are by far the best studied subgroup with established knowledge of their molecular structure and their mode of pore-forming action. However, the current view of necrotic action by actinoporins may not be the only mechanism that induces cell death since there is increasing evidence showing that pore-forming toxins can induce either necrosis or apoptosis in a cell-type, receptor and dose-dependent manner. In this review, we focus on the response of the cellular immune system to the cnidarian pore-forming toxins and the signaling pathways that might be involved in these cellular responses. Since PFTs represent potential candidates for targeted toxin therapy for the treatment of numerous cancers, we also address the challenge to overcoming the immunogenicity of these toxins when used as therapeutics.
    Matched MeSH terms: Pore Forming Cytotoxic Proteins/immunology*; Pore Forming Cytotoxic Proteins/chemistry
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