Displaying publications 1881 - 1900 of 8282 in total

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  1. Chen YH, Chen HJ, Yang CY, Shiu JH, Hoh DZ, Chiang PW, et al.
    Environ Microbiol, 2022 Mar;24(3):1308-1325.
    PMID: 34708512 DOI: 10.1111/1462-2920.15824
    Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.
    Matched MeSH terms: RNA, Ribosomal, 16S/genetics
  2. Manuvera VA, Kharlampieva DD, Bobrovsky PA, Grafskaia EN, Brovina KA, Lazarev VN
    Biochem Biophys Res Commun, 2024 Feb 12;696:149473.
    PMID: 38241814 DOI: 10.1016/j.bbrc.2024.149473
    The saliva of the medicinal leech contains various anticoagulants. Some of them, such as hirudin, are well known. However, it is reasonable to believe that not all anticoagulant proteins from medicinal leech saliva have been identified. We previously performed a comprehensive study of the transcriptome, genome, and proteome of leech salivary gland cells, which led to the discovery of several previously unknown hypothetical proteins that may have anticoagulant properties. Subsequently, we obtained a series of recombinant proteins and investigated their impact on coagulation in in vitro assays. We identified a previously undescribed protein that exhibited a high ability to suppress coagulation. The His-tagged recombinant protein was expressed in Escherichia coli and purified using metal chelate chromatography. To determine its activity, commonly used coagulation methods were used: activated partial thromboplastin time, prothrombin time, and thrombin inhibition clotting assay. Clotting and chromogenic assays for factor Xa inhibition were performed to evaluate anti-Xa activity. We used recombinant hirudin as a control anticoagulant protein in all experiments. The new protein showed significantly greater inhibition of coagulation than hirudin at the same molar concentrations in the activated partial thrombin time assay. However, hirudin demonstrated better results in the direct thrombin inhibition test, although the tested protein also exhibited the ability to inhibit thrombin. The chromogenic analysis of factor Xa inhibition revealed no activity, whereas the clotting test for factor Xa showed the opposite result. Thus, a new powerful anticoagulant protein has been discovered in the medicinal leech. This protein is homologous to antistatin, with 28 % identical amino acid residues. The recombinant protein was expressed in E. coli. This protein is capable of directly inhibiting thrombin, and based on indirect evidence, other proteases of the blood coagulation cascade have been identified.
    Matched MeSH terms: Escherichia coli/genetics
  3. Kuwata K, Lum WM, Takahashi K, Benico G, Takahashi K, Lim PT, et al.
    Harmful Algae, 2024 Sep;138:102701.
    PMID: 39244236 DOI: 10.1016/j.hal.2024.102701
    Amphidoma languida, a marine thecate dinoflagellate that produces the lipophilic toxin azaspiracids (AZAs), is primarily found in the Atlantic. Although this species has not been recorded in the Asian Pacific, environmental DNAs related to Am. languida have been widely detected in the region by metabarcoding analysis. Their morphology and AZA production remain unclear. In this study, the morphology, ultrastructure, phylogeny, and AZA production of nine Amphidoma strains isolated from Japan, Malaysia, and Philippines were investigated. Phylogenetic trees inferred from rDNAs (SSU, ITS, and LSU rDNA) showed monophyly of the nine Pacific strains and were sister to the Am. languida clade, including the toxigenic strains from the Atlantic. Cells were ellipsoid, 8.7-16.7 µm in length and 7.4-14.0 µm in width, with a conspicuous apical pore complex. A large nucleus in the hyposome, parietal chloroplast with a spherical pyrenoid in the episome, and refractile bodies were observed. Thecal tabulation was typical of Amphidoma, Po, cp, X, 6', 6'', 6C, 5S, 6''', 2''''. A ventral pore was located on the anterior of 1' plate, beside the suture to 6' plate. The presence of a ventral depression, on the anterior of anterior sulcal plate, was different from Am. languida. A large antapical pore, containing approximately 10 small pores, was observed. Cells were apparently smaller than Am. trioculata, a species possessing three pores (ventral pore, ventral depression, and antapical pore). TEM showed the presence of crystalline structures, resembling guanine crystals, and cytoplasmic invaginations into the pyrenoid matrix. Flagellar apparatus lacking the striated root connective is similar to peridinioids and related dinoflagellates. AZAs were not detected from the Pacific strains by LC-MS/MS. This non-toxigenic Amphidoma species, here we propose as Amphidoma fulgens sp. nov., is widely distributed in the Asian Pacific. Moreover, molecular comparison also suggested that most of the environmental DNA sequences previously reported as Am. languida or related sequences from the Asian Pacific were attributable to Am. fulgens.
    Matched MeSH terms: DNA, Ribosomal/genetics
  4. Aldoghachi AF, Yanagisawa D, Pahrudin Arrozi A, Abu Bakar ZH, Taguchi H, Ishigaki S, et al.
    Biochem Biophys Res Commun, 2024 Jan 29;694:149392.
    PMID: 38142581 DOI: 10.1016/j.bbrc.2023.149392
    Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of β-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of β-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to β-cell ratio and the number of apoptotic β-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic β-cells apoptosis.
    Matched MeSH terms: Thioredoxins/genetics
  5. Pendi FH, Hussain H
    BMC Res Notes, 2024 Sep 05;17(1):251.
    PMID: 39238033 DOI: 10.1186/s13104-024-06924-3
    OBJECTIVE: Sago palm (Metroxylon sagu Rottb.) is one of the most important economic crops abundantly found in Mukah, Sarawak, Malaysia. The robustness of the palm triggered the Sarawak government's selection as one of the state's commodity crops, with the opening of several sago palm plantations. However, stunted (non-trunking) palms were reported in several sago palm plantations despite attaining a maturity period of more than ten years after cultivation. Research targeting this problem has been conducted in various fields, yet information on molecular mechanisms is still scarce. This study aimed to determine the genes responsible for sago palm's normal phenotype (trunking) by attaining leaf transcriptomes from samples of all trunking sago palms from different sago palm plantations.

    DATA DESCRIPTION: The conventional CTAB method was employed in the present investigation to extract total RNA from leaf tissues. Transcriptome sequencing was conducted on the Illumina NovaSeq 6000 platform. Differential expression analysis was performed using the DESeq2 package. A total of 6,119 differentially expressed genes, comprising 4,384 downregulated and 1,735 upregulated genes, were expressed in all three sago palm datasets. The datasets provide insights into the commonly expressed genes among trunking sago palms.

    Matched MeSH terms: Plant Leaves/genetics
  6. Voon K, Ng QM, Yu M, Wang LF, Chua KB
    PMID: 23077814
    Viruses in the family Picornaviridae are classified into nine genera. Within the family Picornaviridae, two species: Encephalomyocarditis virus and Theilovirus, are listed under the genus Cardiovirus. A novel Theilovirus, Saffold virus (SAFV), was first reported in 2007. Since then, numerous SAFV isolates have been detected around the world and genetic recombinations have been reported among them. In 2009, SAFV-Penang was isolated from a febrile child with influenza-like illness in Malaysia. SAFV-Penang is a genotype 3 SAFV. In this study we investigated the genome features of SAFV-Penang to exclude the possibility it is a recombinant variant. SAFV-Penang was found not to be a recombinant variant but to have three unique non-synonymous substitutions, alanine [A689], lysine [K708] and isoleucine [I724] in the VP1 protein.
    Matched MeSH terms: Theilovirus/genetics*
  7. Norahmad NA, Abdullah NR, Yaccob N, Jelip J, Dony JF, Ruslan KF, et al.
    PMID: 22299399
    Chloroquine (CQ) remains the first line drug for the prevention and treatment of malaria in Malaysia in spite of the fact that resistance to CQ has been observed in Malaysia since the 1960s. CQ-resistance is associated with various mutations in pfcrt, which encodes a putative transporter located in the digestive vacuolar membrane of P. falciparum. Substitution of lysine (K) to threonine (T) at amino acid 76 (K76T) in pfcrt is the primary genetic marker conferring resistance to CQ. To determine the presence of T76 mutation in pfcrt from selected areas of Kalabakan, Malaysia 619 blood samples were screened for P. falciparum, out of which 31 were positive. Blood samples were collected on 3 MM Whatman filter papers and DNA was extracted using QIAmp DNA mini kit. RFLP-PCR for the detection of the CQ-resistant T76 and sensitive K76 genotype was carried out. Twenty-five samples were shown to have the point mutation in pfcrt whereas the remaining samples were classified as CQ-sensitive (wild-type). In view of the fact that CQ is the first line anti-malarial drug in Malaysia, this finding could be an important indication that treatment with CQ may no longer be effective in the future.
    Matched MeSH terms: Drug Resistance/genetics; Plasmodium falciparum/genetics*; Protozoan Proteins/genetics*; Malaria, Falciparum/genetics*; Genes, Protozoan/genetics*; Membrane Transport Proteins/genetics*; Multidrug Resistance-Associated Proteins/genetics
  8. Khor SY, Lim YS, Jegathesan M
    PMID: 7147009
    Forty samples of Malaysian cooked foods were examined for the presence of antibiotic-resistant coliforms and R plasmids. Twenty seven (68%) of the foods had antibiotic-resistant coliforms and 5 (13%) had R plasmids. Nineteen samples (48%) had total bacterial counts over 10(6) per gm and in 5 samples, no coliforms were detected. Our findings show that cooked food may be one possible way by which R plasmids are spread. The control of the spread of R plasmids is discussed.
    Matched MeSH terms: Enterobacteriaceae/genetics*
  9. Baimai V, Green CA, Andre RG, Harrison BA, Peyton EL
    PMID: 6543543
    Recent studies on cytogenetics, behavioral, geographical and distinct morphological characters on adult, pupal and larval stages have revealed that "balabacensis" is a species complex. Anopheles dirus the mainland species, is distributed widely in Thailand and is renowned for its role as primary vector of human malarial parasites. Further, evidence from cytogenetic and taxonomic studies suggests that "An. dirus" is a species complex comprising at least four distinct species provisionally designated: dirus A, B, C and D. These cryptic species are distinguishable only partially morphologically, but can be separated on the basis of metaphase chromosomes using the Giemsa and Hoechst 33258 staining techniques. Apparently, these siblings show distinct patterns of geographic distribution in Thailand and Peninsular Malaysia. The recognition of dirus as a complex of species in Thailand and Peninsular Malaysia requires a re-evaluation of the role that the individual members of this complex have in the transmission of malaria parasites in this region. Cytological analysis of gene rearrangements in ovarian polytene chromosomes has shown that An. maculatus is a sibling-species complex consisting of at least four species in Thailand provisionally designated: maculatus A, B, C and G. These siblings are sympatric in some populations. Furthermore, species B is so highly polymorphic for chromosome rearrangements that four geographic forms can be recognized. It is not known whether these four forms are subspecies or yet further species within the species B complex. These sibling-species must be differentiated in order to understand any differential capabilities in their transmission of human malaria parasites. Anopheles nivipes was elevated from synonymy under An. philippinensis to full species status by Reid, a decision recently confirmed by cross mating experiments. The Thailand Malaria Division does not differentiate these two species and only identifies An. philippinensis, yet, An. nivipes is by far the most common of the two species in Thailand. Furthermore, preliminary surveys of the ovarian polytene chromosomes of several widely separated populations of An. nivipes in Thailand have revealed at least two distinct chromosomal types of nivipes based on fixed inversions on the X chromosomes.
    Matched MeSH terms: Anopheles/genetics*
  10. Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.
    J Pathol, 2024 Mar;262(3):271-288.
    PMID: 38230434 DOI: 10.1002/path.6238
    Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
    Matched MeSH terms: Biomarkers, Tumor/genetics
  11. Md Yusuf N, Azman AN, Abdul Aziz AA, Ahmad Fuad FA, Nasarudin RN, Hisam S
    PLoS One, 2024;19(8):e0306975.
    PMID: 39146276 DOI: 10.1371/journal.pone.0306975
    Malaria, an ancient mosquito-borne illness caused by Plasmodium parasites, is mostly treated with Artemisinin Combination Therapy (ACT). However, Single Nucleotide Polymorphisms (SNPs) mutations in the P. falciparum Kelch 13 (PfK13) protein have been associated with artemisinin resistance (ART-R). Therefore, this study aims to generate PfK13 recombinant proteins incorporating of two specific SNPs mutations, PfK13-V494I and PfK13-N537I, and subsequently analyze their binding interactions with artemisinin (ART). The recombinant proteins of PfK13 mutations and the Wild Type (WT) variant were expressed utilizing a standard protein expression protocol with modifications and subsequently purified via IMAC and confirmed with SDS-PAGE analysis and Orbitrap tandem mass spectrometry. The binding interactions between PfK13-V494I and PfK13-N537I propeller domain proteins ART were assessed through Isothermal Titration Calorimetry (ITC) and subsequently validated using fluorescence spectrometry. The protein concentrations obtained were 0.3 mg/ml for PfK13-WT, 0.18 mg/ml for PfK13-V494I, and 0.28 mg/ml for PfK13-N537I. Results obtained for binding interaction revealed an increased fluorescence intensity in the mutants PfK13-N537I (83 a.u.) and PfK13-V494I (143 a.u.) compared to PfK13-WT (33 a.u.), indicating increased exposure of surface proteins because of the looser binding between PfK13 protein mutants with ART. This shows that the PfK13 mutations may induce alterations in the binding interaction with ART, potentially leading to reduced effectiveness of ART and ultimately contributing to ART-R. However, this study only elucidated one facet of the contributing factors that could serve as potential indicators for ART-R and further investigation should be pursued in the future to comprehensively explore this complex mechanism of ART-R.
    Matched MeSH terms: Drug Resistance/genetics
  12. Shohaimi SA, Leow BL, Mohd Yusop FF, Sidik MR, Barker Z, Mohd Saeid FH
    Trop Biomed, 2024 Jun 01;41(2):183-189.
    PMID: 39154271 DOI: 10.47665/tb.41.2.008
    Low pathogenic avian influenza (LPAI) subtype H9N2 is a causative agent that has raised increasing concern about its impact on poultry and potential public health threats. Even though H9N2 is endemic in Peninsular Malaysia, it was first reported in Sabah in August 2022, after an outbreak associated with high mortality in broiler chickens. In the present study, based on the hemagglutinin (HA) gene, we report the genetic variations and phylogenetic analysis of a H9N2 virus isolated from broiler chickens in Sabah. The sequence analysis of the HA gene revealed a 98% similarity to the H9N2 virus recently isolated from China in 2018. The amino acids in the HA cleavage site displayed a characteristic LPAI motif (PARSSR/ GLF). Notably, at position 226, the isolate had amino acid Leucine (L) demonstrating its ability to bind to the receptor of mammals, resulting in the potential risk of transmission to humans. In addition, the H9N2 isolate harboured seven potential N-glycosylation sites. The phylogenetic analysis revealed that the isolate belonged to clade h9.4.2.5 in the Y280 lineage, similar to previously reported in Malaysia. However, we observed that the isolate in this study falls in a different cluster compared with previous Malaysian isolates, suggesting different source of H9N2 introduction into the country. This prompts us to propose continuous and thorough surveillance of poultry across the country and the necessity of implementing farm biosecurity to minimize economic losses and potential threats to public health.
    Matched MeSH terms: Hemagglutinin Glycoproteins, Influenza Virus/genetics
  13. Rathod L, Mishra S, Samuel S, Yadav K, Sharma G, Singh S, et al.
    Trop Biomed, 2024 Jun 01;41(2):209-213.
    PMID: 39154275 DOI: 10.47665/tb.41.2.012
    Monitoring mosquito host choice to identify high-risk groups for different vector-borne diseases is important to devise vector control strategies and disease management. The present study was conducted to develop and validate a PCR-based method to identify human sex in blood-fed Aedes aegypti mosquitoes. Several human genes present in both the X and Y chromosomes were screened and diagnostic PCR primers were successfully designed and amplified for the human STS gene. The limit of detection of this PCR assay was carried out on Ae. aegypti fed with human blood up to 5 days (120 hours) post blood-meal under laboratory condition. The efficiency of this PCR assay was evaluated in field-collected Ae. aegypti mosquitoes and compared with other existing methods. The developed PCR primers can successfully amplify and distinguish human sex in mosquitoes up to 72 hours after a blood meal, with an amplified product of 627bp and 298bp for male (XY) and 627bp for female (XX) blood-fed mosquitoes. Further, validation of this assay in field-collected Ae. aegypti mosquitoes revealed that this assay could detect human sex in mosquito blood meal substantially more efficiently (c2 = 4.5, p = 0.034) than other PCR based assay. The newly developed PCR assay highly specific to human DNA and can distinguish male and female DNA for up to 72 hours. This assay can be is used for identifying highrisk groups and extended to other medically important hematophagous insects to assess their role in disease transmission and epidemic preparedness.
    Matched MeSH terms: Mosquito Vectors/genetics
  14. Saravanan C, S M N Mydin RB, Mohamed Sheriff NR, Kaur G, Singh Dhaliwal S, Musa MY
    Clin Chim Acta, 2025 Jan 15;565:119952.
    PMID: 39216814 DOI: 10.1016/j.cca.2024.119952
    Salivaomics is a promising method for the early detection and monitoring of head and neck cancer (HNC). By analyzing salivary proteomics, RNA, and DNA, it identifies biomarkers that distinguish HNC patients from healthy individuals. Saliva's non-invasive, easily collectible nature and affordability make it an advantageous screening tool. Multiomics approaches, which explore genetic mutations, gene expression patterns, protein profiles, and metabolite levels, provide a comprehensive molecular perspective that enhances clinical applicability. The approaches enhance the precision of diagnoses, enable the development and application of targeted therapies, and contribute to the overall advancement of personalized medicine. Despite its potential, larger-scale studies are essential for validating biomarkers, and assessing sensitivity, accuracy, and specificity in detecting HNC. This review highlights salivaomics' potential as a non-invasive, accessible biological sample for early disease detection in HNC and underscores the value of multiomics in advancing this research. Salivaomics offers significant insights into the underlying mechanisms of HNC, enabling the discovery of robust, non-invasive biomarkers for improved disease management.
    Matched MeSH terms: Biomarkers, Tumor/genetics
  15. Goldtzvik Y, Sen N, Lam SD, Orengo C
    Curr Opin Struct Biol, 2023 Aug;81:102640.
    PMID: 37354790 DOI: 10.1016/j.sbi.2023.102640
    Proteins provide the basis for cellular function. Having multiple versions of the same protein within a single organism provides a way of regulating its activity or developing novel functions. Post-translational modifications of proteins, by means of adding/removing chemical groups to amino acids, allow for a well-regulated and controlled way of generating functionally distinct protein species. Alternative splicing is another method with which organisms possibly generate new isoforms. Additionally, gene duplication events throughout evolution generate multiple paralogs of the same genes, resulting in multiple versions of the same protein within an organism. In this review, we discuss recent advancements in the study of these three methods of protein diversification and provide illustrative examples of how they affect protein structure and function.
    Matched MeSH terms: Protein Isoforms/genetics
  16. Soo OYM, Gastineau R, Verdon G, Winsor L, Justine JL
    Zootaxa, 2023 May 03;5277(3):585-599.
    PMID: 37518300 DOI: 10.11646/zootaxa.5277.3.11
    We present here the first observation of Bipalium admarginatum de Beauchamp, 1933 since its original description 90 years ago. Three specimens were found on Perhentian Kecil Island, off Terengganu State, Malaysia and photographed in the field, and two were collected. This report thus includes the first colour photographs published for this species, from a locality close to the type-locality, Tioman Island (which is ca. 200 km south of the locality in this study, on the east coast of Peninsula Malaysia). We describe the external morphology and colour pattern of the species, which correspond well to the original description, itself based only on two preserved specimens. We performed an in-depth molecular characterisation of the species, including its complete mitochondrial genome, the 18S sequence and elongation 1-alpha (EF1-α) sequence. In addition, EF1-α sequences were also retrieved for 5 additional geoplanid species. No tRNA-Thr could be detected in the mitogenome of B. admarginatum, a lack already reported in several species of geoplanids, but we found a 13 bp sequence that contains the anticodon loop and seems to be conserved among geoplanids and might thus possibly represent a non-canonical undetected tRNA. We discuss the difficulties encountered in trying to reconstruct the cluster of nuclear ribosomal genes, a problem already mentioned for other Triclads. Three phylogenies, based respectively on all mitochondrial proteins, 18S, and EF1-α, were computed; the position of B. admarginatum within the Bipaliinae was confirmed in each tree, as sister-group to various bipaliine species according to the sequences available for each tree. In the mitochondrial proteins tree, which had high support, B. admarginatum was sister to Bipalium kewense and Diversibipalium multilineatum.
    Matched MeSH terms: RNA, Transfer/genetics
  17. Tan TC, Chandrasekaran L, Leung YY, Purbojati R, Pettersson S, Low AHL
    Clin Exp Rheumatol, 2023 Aug;41(8):1578-1588.
    PMID: 36826808 DOI: 10.55563/clinexprheumatol/jof7nx
    OBJECTIVES: The early gastrointestinal (GI) manifestation of systemic sclerosis (SSc) suggests a possible GI microbiota engagement in the pathophysiology and/or progression of SSc. Previous studies have revealed dysbiosis among Caucasian SSc patients. This study extends these findings to Asian SSc patients.

    METHODS: Adult SSc patients, stratified according to 1) on immunosuppressive (On-IS) drugs or 2) no immunosuppressive drugs (No-IS), and age-and-sex-matched healthy controls (HC) were recruited. Metagenomic sequencing of stool DNA was compared between SSc patients and HC, and between SSc (On-IS) and (No-IS) patients. Alpha and beta-diversity, taxonomic and functional profiling were evaluated.

    RESULTS: Twenty-three female SSc patients (12 On-IS; 11 No-IS; 5 diffuse and 18 limited SSc subtype) and 19 female HC, with median age of 54 years and 56 years, respectively, were recruited. Median SSc disease duration was 3.3 years. Alpha diversity was significantly higher in SSc versus HC (p=0.014) and in SSc (No-IS) versus HC (p=0.006). There was no significant difference in beta diversity between SSc and HC (p=0.307). At the phyla level, there were significantly increased abundance of Firmicutes and Actinobacteria in SSc versus HC, and reduced abundance of Bacteroidetes (all p<0.001). At the species level, there were significantly increased abundance of several Lactobacillus, Bifidobacterium, and Coprococcus species in SSc, and increased abundance of Odoribacter, Bacteroides and Prevotella species in HC. KEGG pathway analysis demonstrated distinct differences between SSc versus HC, and between SSc (No-IS) and SSc (On-IS).

    CONCLUSIONS: Using metagenomic sequencing, our study further underlines distinct alterations in microbiota profiling among Asian SSc patients.

    Matched MeSH terms: Bacteria/genetics
  18. Puan SL, Erriah P, Baharudin MMA, Yahaya NM, Kamil WNIWA, Ali MSM, et al.
    Appl Microbiol Biotechnol, 2023 Sep;107(18):5569-5593.
    PMID: 37450018 DOI: 10.1007/s00253-023-12651-9
    Antibiotic resistance is a growing concern that is affecting public health globally. The search for alternative antimicrobial agents has become increasingly important. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this review, we provide an overview of Bacillus-derived AMPs, including their classification into ribosomal (bacteriocins) and non-ribosomal peptides (lipopeptides and polyketides). Additionally, we delve into the molecular mechanisms of AMP production and describe the key biosynthetic gene clusters involved. Despite their potential, the low yield of AMPs produced under normal laboratory conditions remains a challenge to large-scale production. This review thus concludes with a comprehensive summary of recent studies aimed at enhancing the productivity of Bacillus-derived AMPs. In addition to medium optimization and genetic manipulation, various molecular strategies have been explored to increase the production of recombinant antimicrobial peptides (AMPs). These include the selection of appropriate expression systems, the engineering of expression promoters, and metabolic engineering. Bacillus-derived AMPs offer great potential as alternative antimicrobial agents, and this review provides valuable insights on the strategies to enhance their production yield, which may have significant implications for combating antibiotic resistance. KEY POINTS: • Bacillus-derived AMP is a potential alternative therapy for resistant pathogens • Bacillus produces two main classes of AMPs: ribosomal and non-ribosomal peptides • AMP yield can be enhanced using culture optimization and molecular approaches.
    Matched MeSH terms: Antimicrobial Cationic Peptides/genetics
  19. Goh JJ, Ong HT, Lee BS, Teoh HK
    Malays J Pathol, 2023 Aug;45(2):247-259.
    PMID: 37658534
    INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced.

    OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells.

    MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed.

    RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties.

    CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

    Matched MeSH terms: Interleukin-12/genetics
  20. Pathan RK, Uddin MA, Paul AM, Uddin MI, Hamd ZY, Aljuaid H, et al.
    PLoS One, 2023;18(8):e0290045.
    PMID: 37611023 DOI: 10.1371/journal.pone.0290045
    Monkeypox is a double-stranded DNA virus with an envelope and is a member of the Poxviridae family's Orthopoxvirus genus. This virus can transmit from human to human through direct contact with respiratory secretions, infected animals and humans, or contaminated objects and causing mutations in the human body. In May 2022, several monkeypox affected cases were found in many countries. Because of its transmitting characteristics, on July 23, 2022, a nationwide public health emergency was proclaimed by WHO due to the monkeypox virus. This study analyzed the gene mutation rate that is collected from the most recent NCBI monkeypox dataset. The collected data is prepared to independently identify the nucleotide and codon mutation. Additionally, depending on the size and availability of the gene dataset, the computed mutation rate is split into three categories: Canada, Germany, and the rest of the world. In this study, the genome mutation rate of the monkeypox virus is predicted using a deep learning-based Long Short-Term Memory (LSTM) model and compared with Gated Recurrent Unit (GRU) model. The LSTM model shows "Root Mean Square Error" (RMSE) values of 0.09 and 0.08 for testing and training, respectively. Using this time series analysis method, the prospective mutation rate of the 50th patient has been predicted. Note that this is a new report on the monkeypox gene mutation. It is found that the nucleotide mutation rates are decreasing, and the balance between bi-directional rates are maintained.
    Matched MeSH terms: Monkeypox virus/genetics
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