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  1. Fulltext Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology
    Gormus U, Chaubey A, Shenoy S, Wong YW, Chan LY, Choo BP, et al.
    Curr Issues Mol Biol, 2021 Aug 17;43(2):958-964.
    PMID: 34449543 DOI: 10.3390/cimb43020068
    Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35-100.00%); 100.00% sensitivity for T18 (71.51-100.00%); and 100.00% sensitivity for T13 analyses (66.37-100.00%). The specificities were >99% for each trisomy (99.7% (99.01-99.97%) for T21; 99.5% (98.62-99.85%) for T18; 99.7% (99.03-99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.
  2. An Overview of Hepatitis B Virus Surface Antigen Mutant in the Asia Pacific
    Hudu SA, Malik YA, Niazlin MT, Harmal NS, Sekawi Z
    Curr Issues Mol Biol, 2014;16:69-78.
    PMID: 24014801
    Hepatitis B virus infection is a serious health problem worldwide, and more than 350 million people are chronic carriers, constituting a major global threat. Southeast Asia and the Western Pacific have the highest levels of endemicity in the world, with an estimated seroprevalence ranging between 2% and 31%. Mutations in the hepatitis B surface antigen (HBsAg) have been reported in many parts of the world but are most common in Asian infants; such mutants have several clinical effects, such as the development of hepatocellular carcinoma. Diagnostic failures by commercial assays have reduced the diagnostic effectiveness of HBsAg detection. For example the substitution of an amino acid in the major hydrophilic region of the S gene reduces the binding of hepatitis B surface antibodies leading to immune escape. The safety of blood transfusion may be compromised by current screening tests due to escape from being neutralised by antibodies induced by HBsAg mutants, and undetectable levels of viral surface protein. Data on the epidemiology of HBsAg mutation in Asia Pacific are scant; however, this manuscript has reviewed the available information on the epidemiology of HBsAg mutation in Asia Pacific.
  3. Extended Spectrum Beta-lactamases: Definition, Classification and Epidemiology
    Ghafourian S, Sadeghifard N, Soheili S, Sekawi Z
    Curr Issues Mol Biol, 2015;17:11-21.
    PMID: 24821872
    Extended spectrum beta-lactamases (ESBLs) are defined as enzymes produced by certain bacteria that are able to hydrolyze extended spectrum cephalosporin. They are therefore effective against beta-lactam antibiotics such as ceftazidime, ceftriaxone, cefotaxime and oxyimino-monobactam. The objective of the current review is to provide a better understanding of ESBL and the epidemiology of ESBL producing organisms which are among those responsible for antibiotic resistant strains. Globally, ESBLs are considered to be problematic, particularly in hospitalized patients. There is an increasing frequency of ESBL in different parts of the world. The high risk patients are those contaminated with ESBL producer strains as it renders treatment to be ineffective in these patients. Thus, there an immediate needs to identify EBSL and formulate strategic policy initiatives to reduce their prevalence.
  4. Allele Mining Strategies: Principles and Utilisation for Blast Resistance Genes in Rice (Oryza sativa L.)
    Ashkani S, Yusop MR, Shabanimofrad M, Azady A, Ghasemzadeh A, Azizi P, et al.
    Curr Issues Mol Biol, 2015;17:57-73.
    PMID: 25706446
    Allele mining is a promising way to dissect naturally occurring allelic variants of candidate genes with essential agronomic qualities. With the identification, isolation and characterisation of blast resistance genes in rice, it is now possible to dissect the actual allelic variants of these genes within an array of rice cultivars via allele mining. Multiple alleles from the complex locus serve as a reservoir of variation to generate functional genes. The routine sequence exchange is one of the main mechanisms of R gene evolution and development. Allele mining for resistance genes can be an important method to identify additional resistance alleles and new haplotypes along with the development of allele-specific markers for use in marker-assisted selection. Allele mining can be visualised as a vital link between effective utilisation of genetic and genomic resources in genomics-driven modern plant breeding. This review studies the actual concepts and potential of mining approaches for the discovery of alleles and their utilisation for blast resistance genes in rice. The details provided here will be important to provide the rice breeder with a worthwhile introduction to allele mining and its methodology for breakthrough discovery of fresh alleles hidden in hereditary diversity, which is vital for crop improvement.
  5. Toxin-antitoxin Systems: Classification, Biological Function and Application in Biotechnology
    Ghafourian S, Raftari M, Sadeghifard N, Sekawi Z
    Curr Issues Mol Biol, 2014;16:9-14.
    PMID: 23652423
    The toxin-antitoxin (TA) systems are systems in which an unstable antitoxin inhibits a stable toxin. This review aims to introduce the TA system and its biological application in bacteria. For this purpose, first we introduce a new classification for the TA systems based on how the antitoxin can neutralize the toxin, we then describe the functions of TA systems and finally review the application of these systems in biotechnology.
  6. A Critical Review of the Concept of Transgenic Plants: Insights into Pharmaceutical Biotechnology and Molecular Farming
    Abiri R, Valdiani A, Maziah M, Shaharuddin NA, Sahebi M, Yusof ZN, et al.
    Curr Issues Mol Biol, 2016;18:21-42.
    PMID: 25944541
    Using transgenic plants for the production of high-value recombinant proteins for industrial and clinical applications has become a promising alternative to using conventional bioproduction systems, such as bacteria, yeast, and cultured insect and animal cells. This novel system offers several advantages over conventional systems in terms of safety, scale, cost-effectiveness, and the ease of distribution and storage. Currently, plant systems are being utilised as recombinant bio-factories for the expression of various proteins, including potential vaccines and pharmaceuticals, through employing several adaptations of recombinant processes and utilizing the most suitable tools and strategies. The level of protein expression is a critical factor in plant molecular farming, and this level fluctuates according to the plant species and the organs involved. The production of recombinant native and engineered proteins is a complicated procedure that requires an inter- and multi-disciplinary effort involving a wide variety of scientific and technological disciplines, ranging from basic biotechnology, biochemistry, and cell biology to advanced production systems. This review considers important plant resources, affecting factors, and the recombinant-protein expression techniques relevant to the plant molecular farming process.
  7. Fulltext A Link between Mitochondrial Dysregulation and Idiopathic Autism Spectrum Disorder (ASD): Alterations in Mitochondrial Respiratory Capacity and Membrane Potential
    Hassan H, Zakaria F, Makpol S, Karim NA
    Curr Issues Mol Biol, 2021 Dec 16;43(3):2238-2252.
    PMID: 34940131 DOI: 10.3390/cimb43030157
    Autism spectrum disorder (ASD) is a neurological disorder triggered by various factors through complex mechanisms. Research has been done to elucidate the potential etiologic mechanisms in ASD, but no single cause has been confirmed. The involvement of oxidative stress is correlated with ASD and possibly affects mitochondrial function. This study aimed to elucidate the link between mitochondrial dysregulation and idiopathic ASD by focusing on mitochondrial respiratory capacity and membrane potential. Our findings showed that mitochondrial function in the energy metabolism pathway was significantly dysregulated in a lymphoblastoid cell line (LCL) derived from an autistic child (ALCL). Respiratory capacities of oxidative phosphorylation (OXPHOS), electron transfer of the Complex I and Complex II linked pathways, membrane potential, and Complex IV activity of the ALCL were analyzed and compared with control cell lines derived from a developmentally normal non-autistic sibling (NALCL). All experiments were performed using high-resolution respirometry. Respiratory capacities of OXPHOS, electron transfer of the Complex I- and Complex II-linked pathways, and Complex IV activity of the ALCL were significantly higher compared to healthy controls. Mitochondrial membrane potential was also significantly higher, measured in the Complex II-linked pathway during LEAK respiration and OXPHOS. These results indicate the abnormalities in mitochondrial respiratory control linking mitochondrial function with autism. Correlating mitochondrial dysfunction and autism is important for a better understanding of ASD pathogenesis in order to produce effective interventions.
  8. Fulltext Expression of Endogenous Putative TSH Binding Protein in Orbit
    Draman MS, Grennan-Jones F, Taylor P, Muller I, Evans S, Haridas A, et al.
    Curr Issues Mol Biol, 2021 Oct 27;43(3):1794-1804.
    PMID: 34889904 DOI: 10.3390/cimb43030126
    Thyroid stimulating antibodies (TSAB) cause Graves' disease and contribute to Graves' Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2β5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = -0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. β5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR.
  9. Fulltext Transcriptomic Signature of Horseshoe Crab Carcinoscorpius rotundicauda Hemocytes' Response to Lipopolysaccharides
    Sarmiento ME, Chin KL, Lau NS, Ismail N, Norazmi MN, Acosta A, et al.
    Curr Issues Mol Biol, 2022 Nov 25;44(12):5866-5878.
    PMID: 36547060 DOI: 10.3390/cimb44120399
    Carcinoscorpius rotundicauda (C. rotundicauda) is one of the four species of horseshoe crabs (HSCs). The HSC hemocytes store defense molecules that are released upon encountering invading pathogens. The HSCs rely on this innate immunity to continue its existence as a living fossil for more than 480 million years. To gain insight into the innate mechanisms involved, transcriptomic analysis was performed on isolated C. rotundicauda hemocytes challenged with lipopolysaccharides (LPS), the main components of the outer cell membrane of gram-negative bacteria. RNA-sequencing with Illumina HiSeq platform resulted in 232,628,086 and 245,448,176 raw reads corresponding to 190,326,253 and 201,180,020 high-quality mappable reads from control and LPS-stimulated hemocytes, respectively. Following LPS-stimulation, 79 genes were significantly upregulated and 265 genes were downregulated. The differentially expressed genes (DEGs) were related to multiple immune functional categories and pathways such as those of the cytoskeleton, Toll and Imd, apoptosis, MAP kinase (MAPK), inositol phosphate metabolism, phagosome, leucocyte endothelial migration, and gram-negative bacterial infection, among others. This study provides important information about the mechanisms of response to LPS, which is relevant for the understanding the HSCs' immune response.
  10. Fulltext Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia
    Prieto JM, Hanafi MMM
    Curr Issues Mol Biol, 2023 Feb 09;45(2):1536-1567.
    PMID: 36826044 DOI: 10.3390/cimb45020099
    Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estimated 1200 medicinal plants. We here explore whether the list of top Malay plants prioritized by the Malaysian government may fulfill the potential of becoming newer, sustainable sources of prostate cancer chemotherapy. These include Andrographis paniculate, Centella asiatica, Clinacanthus nutans, Eurycoma longifolia, Ficus deltoidea, Hibiscus sabdariffa, Marantodes pumilum (syn. Labisia pumila), Morinda citrifolia, Orthosiphon aristatus, and Phyllanthus niruri. Our review highlights the importance of resistance factors such as Smac/DIABLO in cancer progression, the role of the CXCL12/CXCR4 axis in cancer metastasis, and the regulation of PCa cells by some promising terpenes (andrographolide, Asiatic acid, rosmarinic acid), flavonoids (isovitexin, gossypin, sinensetin), and alkylresorcinols (labisiaquinones) among others.
  11. Fulltext Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo
    Zakaria MA, Kiew MC, Rajab NF, Chua EW, Masre SF
    Curr Issues Mol Biol, 2022 Sep 29;44(10):4528-4539.
    PMID: 36286025 DOI: 10.3390/cimb44100310
    Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.
  12. Fulltext Effect of Carcinomas on Autosomal Trait Screening: A Review Article
    Alhatim H, Abdullah MNH, Abu Bakar S, Amer SA
    Curr Issues Mol Biol, 2023 Sep 04;45(9):7275-7285.
    PMID: 37754244 DOI: 10.3390/cimb45090460
    This review highlights the effect of carcinomas on the results of the examination of autosomal genetic traits for identification and paternity tests when carcinoid tissue is the only source and no other samples are available. In DNA typing or genetic fingerprinting, variable elements are isolated and identified within the base pair sequences that form the DNA. The person's probable identity can be determined by analysing nucleotide sequences in particular regions of DNA unique to everyone. Genetics plays an increasingly important role in the risk stratification and management of carcinoma patients. The available information from previous studies has indicated that in some incidents, including mass disasters and crimes such as terrorist incidents, biological evidence may not be available at the scene of the accident, except for some unknown human remains found in the form of undefined human tissues. If these tissues have cancerous tumours, it may affect the examination of the genetic traits derived from these samples, thereby resulting in a failure to identify the person. Pathology units, more often, verify the identity of the patients who were diagnosed with cancer in reference to their deceased tumorous relatives. Genetic fingerprinting (GF) is also used in paternity testing when the alleged parent disappeared or died and earlier was diagnosed and treated for cancer.
  13. Fulltext Overexpression of OLIG2 and MYT1L Transcription Factors Enhance the Differentiation Potential of Human Mesenchymal Stem Cells into Oligodendrocytes
    Fahim I, Ishaque A, Ramzan F, Shamsuddin SABA, Ali A, Salim A, et al.
    Curr Issues Mol Biol, 2023 May 07;45(5):4100-4123.
    PMID: 37232730 DOI: 10.3390/cimb45050261
    BACKGROUND: Demyelinating diseases represent a broad spectrum of disorders and are characterized by the loss of specialized glial cells (oligodendrocytes), which eventually leads to neuronal degeneration. Stem cell-based regenerative approaches provide therapeutic options to regenerate demyelination-induced neurodegeneration.

    OBJECTIVES: The current study aims to explore the role of oligodendrocyte-specific transcription factors (OLIG2 and MYT1L) under suitable media composition to facilitate human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) differentiation toward oligodendrocyte for their potential use to treat demyelinating disorders.

    METHODOLOGY: hUC-MSCs were isolated, cultured, and characterized based on their morphological and phenotypic characteristics. hUC-MSCs were transfected with OLIG2 and MYT1L transcription factors individually and in synergistic (OLIG2 + MYT1L) groups using a lipofectamine-based transfection method and incubated under two different media compositions (normal and oligo induction media). Transfected hUC-MSCs were assessed for lineage specification and differentiation using qPCR. Differentiation was also analyzed via immunocytochemistry by determining the expression of oligodendrocyte-specific proteins.

    RESULTS: All the transfected groups showed significant upregulation of GFAP and OLIG2 with downregulation of NES, demonstrating the MSC commitment toward the glial lineage. Transfected groups also presented significant overexpression of oligodendrocyte-specific markers (SOX10, NKX2.2, GALC, CNP, CSPG4, MBP, and PLP1). Immunocytochemical analysis showed intense expression of OLIG2, MYT1L, and NG2 proteins in both normal and oligo induction media after 3 and 7 days.

    CONCLUSIONS: The study concludes that OLIG2 and MYT1L have the potential to differentiate hUC-MSCs into oligodendrocyte-like cells, which is greatly facilitated by the oligo induction medium. The study may serve as a promising cell-based therapeutic strategy against demyelination-induced neuronal degeneration.

  14. Biodistribution of Fluorescent Albumin Nanoparticles among Organs of Laboratory Animals after Intranasal and Peroral Administration
    Morozova O, Isaeva E, Klinov D
    Curr Issues Mol Biol, 2023 Oct 11;45(10):8227-8238.
    PMID: 37886962 DOI: 10.3390/cimb45100519
    Natural, environmental and engineered nanoparticles (NP) penetrate into cells by endocytosis and induce innate immunity. The behaviour of the nanomaterials both in vitro and in vivo should be assessed. Our goal was to study protein NP stability in biological fluids and distribution in organs of animals after intranasal and oral administration. Bovine serum albumin (BSA) was labelled with the fluorescent dye RhoB and NP were fabricated by nanoprecipitation. The fluorescent protein NPwere administered intranasally and orally in laboratory-outbred mice ICR and rabbits. RhoB-BSA NP distribution in organs was detected using spectrofluorometry and fluorescent microscopy. Innate immunity was evaluated using reverse transcription with random hexanucleotide primer and subsequent real-time PCR with specific fluorescent hydrolysis probes. The labelled BSA NP were shown to remain stable in blood sera and nasopharyngeal swabs for 5 days at +37 °C. In vivo the maximal accumulation was found in the brain in 2 days posttreatment without prevalent accumulation in olfactory bulbs. For the intestine, heart and liver, the BSA NP accumulation was similar in 1 and 2 days, whereas for kidney samples even decreased after 1 day. Both intranasal and peroral administration of RhoB-BSA NP did not induce innate immunity. Thus, after intranasal or oral instillation RhoB-BSA NP were found mainly in the brain and intestine without interferon gene expression.
  15. Fulltext Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression
    Kumarasamy G, Ismail MN, Tuan Sharif SE, Desire C, Mittal P, Hoffmann P, et al.
    Curr Issues Mol Biol, 2023 Apr 20;45(4):3603-3627.
    PMID: 37185759 DOI: 10.3390/cimb45040235
    Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression.
  16. Fulltext Multilocus Sequence Analysis and Detection of Copper Ion Resistance of Xanthomonas phaseoli pv. manihotis Causing Bacterial Blight in Cassava
    Shi T, Li C, Wang G, Huang G
    Curr Issues Mol Biol, 2023 Jun 28;45(7):5389-5402.
    PMID: 37504258 DOI: 10.3390/cimb45070342
    Cassava (Manihot esculenta Crantz) is an important tropical tuber crop around the world. Cassava bacterial blight, caused by Xanthomonas phaseoli pv. manihotis, is a key disease that influences cassava production worldwide. Between 2008 and 2020, 50 X. phaseoli pv. manihotis strains were isolated from diseased plant samples or acquired from China, Uganda, Cambodia, Colombia, Malaysia, and Micronesia. Using multilocus sequence analysis, the genetic diversity of X. phaseoli pv. manihotis strains was evaluated. A neighbor-joining phylogenetic dendrogram was constructed based on partial sequences of five housekeeping genes (atpD-dnaK-gyrB-efp-rpoD). The strains clustered into three groups whose clusters were consistent with atpD and RpoD gene sequences. Group I contained 46 strains from China, Uganda, Cambodia, and Micronesia, and the other two groups were comprised of strains from Colombia and Malaysia, respectively. The resistance of all these strains to copper ion (Cu2+) was determined, the minimal inhibitory concentration was between 1.3 and 1.7 mM, and there was no significant difference between strains from different geographic region. During genome annotation of the X. phaseoli pv. manihotis strain CHN01, homologous gene clusters of copLAB and xmeRSA were identified. The predicted amino acid sequences of two gene clusters were highly homologous with the copper-resistant protein from Xanthomonas strains. CopLAB and xmeRSA were amplified from all these strains, suggesting that the regulation of copper resistance is associated with two distinct metabolic pathways. CopLAB and xmeRSA were highly conserved among strains from different geographic regions, possibly associated with other conserved function.
  17. Fulltext Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease
    Yugavathy N, Abdullah BM, Lim SK, Abdul Gafor AHB, Wong MG, Bavanandan S, et al.
    Curr Issues Mol Biol, 2023 Aug 07;45(8):6550-6563.
    PMID: 37623232 DOI: 10.3390/cimb45080413
    The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.
  18. Fulltext Cloning, Expression and Functional Characterization of a Novel α-Humulene Synthase, Responsible for the Formation of Sesquiterpene in Agarwood Originating from Aquilaria malaccensis
    Sundaraj Y, Abdullah H, Nezhad NG, Rodrigues KF, Sabri S, Baharum SN
    Curr Issues Mol Biol, 2023 Nov 10;45(11):8989-9002.
    PMID: 37998741 DOI: 10.3390/cimb45110564
    This study describes the cloning, expression and functional characterization of α-humulene synthase, responsible for the formation of the key aromatic compound α-humulene in agarwood originating from Aquilaria malaccensis. The partial sesquiterpene synthase gene from the transcriptome data of A. malaccensis was utilized for full-length gene isolation via a 3' RACE PCR. The complete gene, denoted as AmDG2, has an open reading frame (ORF) of 1671 bp and encodes for a polypeptide of 556 amino acids. In silico analysis of the protein highlighted several conserved motifs typically found in terpene synthases such as Asp-rich substrate binding (DDxxD), metal-binding residues (NSE/DTE), and cytoplasmic ER retention (RxR) motifs at their respective sites. The AmDG2 was successfully expressed in the E. coli:pET-28a(+) expression vector whereby an expected band of about 64 kDa in size was detected in the SDS-PAGE gel. In vitro enzyme assay using substrate farnesyl pyrophosphate (FPP) revealed that AmDG2 gave rise to two sesquiterpenes: α-humulene (major) and β-caryophyllene (minor), affirming its identity as α-humulene synthase. On the other hand, protein modeling performed using AlphaFold2 suggested that AmDG2 consists entirely of α-helices with short connecting loops and turns. Meanwhile, molecular docking via AutoDock Vina (Version 1.5.7) predicted that Asp307 and Asp311 act as catalytic residues in the α-humulene synthase. To our knowledge, this is the first comprehensive report on the cloning, expression and functional characterization of α-humulene synthase from agarwood originating from A. malaccensis species. These findings reveal a deeper understanding of the structure and functional properties of the α-humulene synthase and could be utilized for metabolic engineering work in the future.
  19. Fulltext Correction: Sundaraj et al. Cloning, Expression and Functional Characterization of a Novel α-Humulene Synthase, Responsible for the Formation of Sesquiterpene in Agarwood Originating from Aquilaria malaccensis. Curr. Issues Mol. Biol. 2023, 45, 8989-9002
    Sundaraj Y, Abdullah H, Nezhad NG, Rasib AAA, Othman R, Rodrigues KF, et al.
    Curr Issues Mol Biol, 2024 Jul 04;46(7):6960.
    PMID: 39057102 DOI: 10.3390/cimb46070415
    Afiq Adham Abd Rasib and Roohaida Othman were not included as authors in the original publication [...].
  20. The Role of Estrogen across Multiple Disease Mechanisms
    Xiang X, Palasuberniam P, Pare R
    Curr Issues Mol Biol, 2024 Jul 29;46(8):8170-8196.
    PMID: 39194700 DOI: 10.3390/cimb46080483
    Estrogen is a significant hormone that is involved in a multitude of physiological and pathological processes. In addition to its pivotal role in the reproductive system, estrogen is also implicated in the pathogenesis of a multitude of diseases. Nevertheless, previous research on the role of estrogen in a multitude of diseases, including Alzheimer's disease, depression, cardiovascular disease, diabetes, osteoporosis, gastrointestinal diseases, and estrogen-dependent cancers, has concentrated on a single disease area, resulting in a lack of comprehensive understanding of cross-disease mechanisms. This has brought some challenges to the current treatment methods for these diseases, because estrogen as a potential therapeutic tool has not yet fully developed its potential. Therefore, this review aims to comprehensively explore the mechanism of estrogen in these seven types of diseases. The objective of this study is to describe the relationship between each disease and estrogen, including the ways in which estrogen participates in regulating disease mechanisms, and to outline the efficacy of estrogen in treating these diseases in clinical practice. By studying the role of estrogen in a variety of disease mechanisms, it is hoped that a more accurate theoretical basis and clinical guidance for future treatment strategies will be provided, thus promoting the effective management and treatment of these diseases.
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