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Fulltext Complete mitochondrial genome of Dacus vijaysegarani and phylogenetic relationships with congeners and other tephritid fruit flies (Insecta: Diptera)

Yong HS, Chua KO, Song SL, Liew YJ, Eamsobhana P, Chan KG

Mol Biol Rep, 2021 Aug;48(8):6047-6056.
PMID: 34357549 DOI: 10.1007/s11033-021-06608-2

BACKGROUND: Tephritid fruit flies of the genus Dacus are members of the tribe Dacini, subfamily Dacinae. There are some 274 species worldwide, distributed in Africa and the Asia-Pacific. To date, only five complete mitochondrial genomes (mitogenomes) of Dacus fruit flies have been published and are available in the GenBank.
METHODS AND RESULTS: In view of the lack of study on their mitogenome, we sequenced (by next generation sequencing) and annotated the complete mitogenome of D. vijaysegarani from Malaysia to determine its features and phylogenetic relationship. The whole mitogenome of D. vijaysegarani has identical gene order with the published mitogenomes of the genus Dacus, with 13 protein-coding genes, two rRNA genes, 22 tRNAs, a non-coding A + T rich control region, and intergenic spacer and overlap sequences. Phylogenetic analysis based on 15 mitochondrial genes (13 PCGs and two rRNA genes), reveals Dacus, Zeugodacus and Bactrocera forming a distinct clade. The genus Dacus forms a monophyletic group in the subclade containing also the Zeugodacus group; this Dacus-Zeugodacus subclade is distinct from the Bactrocera subclade. D. (Mellesis) vijaysegarani forms a lineage with D. (Mellesis) trimacula in the subcluster containing also the lineage of D. (Mellesis) conopsoides and D. (Callantra) longicornis. D. (Dacus) bivittatus and D. (Didacus) ciliatus form a distinct subcluster. Based on cox1 sequences, the Malaysia and Vietnam taxa of D. vijaysegarani may not be conspecific.
CONCLUSIONS: Overall, the mitochondrial genome of D. vijaysegarani provided essential molecular data that could be useful for further studies for species diagnosis, evolution and phylogeny research of other tephritid fruit flies in the future.

Matched MeSH terms: Base Composition/genetics; Base Sequence/genetics; Diptera/genetics; DNA, Mitochondrial/genetics; Insects/genetics; Tephritidae/genetics*; Genome, Mitochondrial/genetics*
Fulltext Comprehensive literature review of monkeypox

Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Ahmad S, Hasan H, Ahmad Suhaimi NA, et al.

Emerg Microbes Infect, 2022 Dec;11(1):2600-2631.
PMID: 36263798 DOI: 10.1080/22221751.2022.2132882

The current outbreak of monkeypox (MPX) infection has emerged as a global matter of concern in the last few months. MPX is a zoonosis caused by the MPX virus (MPXV), which is one of the Orthopoxvirus species. Thus, it is similar to smallpox caused by the variola virus, and smallpox vaccines and drugs have been shown to be protective against MPX. Although MPX is not a new disease and is rarely fatal, the current multi-country MPX outbreak is unusual because it is occurring in countries that are not endemic for MPXV. In this work, we reviewed the extensive literature available on MPXV to summarize the available data on the major biological, clinical and epidemiological aspects of the virus and the important scientific findings. This review may be helpful in raising awareness of MPXV transmission, symptoms and signs, prevention and protective measures. It may also be of interest as a basis for performance of studies to further understand MPXV, with the goal of combating the current outbreak and boosting healthcare services and hygiene practices.Trial registration: ClinicalTrials.gov identifier: NCT02977715..Trial registration: ClinicalTrials.gov identifier: NCT03745131..Trial registration: ClinicalTrials.gov identifier: NCT00728689..Trial registration: ClinicalTrials.gov identifier: NCT02080767..

Matched MeSH terms: Monkeypox virus/genetics
The diversity of rhizospheric bacterial communities associated with Trichoderma-treated rice fields

Abdullah NS, Doni F, Chua KO, Mispan MS, Saiman MZ, Mohd Yusuf Y, et al.

Lett Appl Microbiol, 2022 Dec;75(6):1645-1650.
PMID: 36073093 DOI: 10.1111/lam.13832

Microbial-based fertilizer has been widely used as a healthier and better alternative to agrochemical products. However, the effects of biofertilizers on the rhizospheric microbiota has rarely been investigated. Thus, the aim of this study was to investigate the effects of symbiotic fungus Trichoderma asperellum SL2-based inoculant on the soil bacterial population through next generation sequencing using a metabarcoding approach. The treatment plots were treated with T. asperellum SL2 spore suspension, while the control plots were treated with sterilized distilled water. The results showed similar bacterial microbiome profiles in the soil of control and T. asperellum SL2-treated plots. In conclusion, the application of the T. asperellum SL2 inoculant had not exerted a negative impact towards the bacterial population as similar observation was reflected in control plots. Nonetheless, future research should be conducted to investigate the effects of repeated application of T. asperellum SL2 over a longer period on the rice microbiota communities.

Matched MeSH terms: Bacteria/genetics
Fulltext Assessing a megadiverse but poorly known community of fishes in a tropical mangrove estuary through environmental DNA (eDNA) metabarcoding

Zainal Abidin DH, Mohd Nor SA, Lavoué S, A Rahim M, Mohammed Akib NA

Sci Rep, 2022 Sep 29;12(1):16346.
PMID: 36175455 DOI: 10.1038/s41598-022-19954-3

Biodiversity surveys are crucial for monitoring the status of threatened aquatic ecosystems, such as tropical estuaries and mangroves. Conventional monitoring methods are intrusive, time-consuming, substantially expensive, and often provide only rough estimates in complex habitats. An advanced monitoring approach, environmental DNA (eDNA) metabarcoding, is promising, although only few applications in tropical mangrove estuaries have been reported. In this study, we explore the advantages and limitations of an eDNA metabarcoding survey on the fish community of the Merbok Estuary (Peninsular Malaysia). COI and 12S eDNA metabarcoding assays collectively detected 178 species from 127 genera, 68 families, and 25 orders. Using this approach, significantly more species have been detected in the Merbok Estuary over the past decade (2010-2019) than in conventional surveys, including several species of conservation importance. However, we highlight three limitations: (1) in the absence of a comprehensive reference database the identities of several species are unresolved; (2) some of the previously documented specimen-based diversity was not captured by the current method, perhaps as a consequence of PCR primer specificity, and (3) the detection of non-resident species-stenohaline freshwater taxa (e.g., cyprinids, channids, osphronemids) and marine coral reef taxa (e.g., holocentrids, some syngnathids and sharks), not known to frequent estuaries, leading to the supposition that their DNA have drifted into the estuary through water movements. The community analysis revealed that fish diversity along the Merbok Estuary is not homogenous, with the upstream more diverse than further downstream. This could be due to the different landscapes or degree of anthropogenic influences along the estuary. In summary, we demonstrated the practicality of eDNA metabarcoding in assessing fish community and structure within a complex and rich tropical environment within a short sampling period. However, some limitations need to be considered and addressed to fully exploit the efficacy of this approach.

Matched MeSH terms: Fishes/genetics
Roles of clock genes in the pathogenesis of Parkinson's disease

Shkodina AD, Tan SC, Hasan MM, Abdelgawad M, Chopra H, Bilal M, et al.

Ageing Res Rev, 2022 02;74:101554.
PMID: 34973458 DOI: 10.1016/j.arr.2021.101554

Parkinson's disease (PD) is a common motor disorder that has become increasingly prevalent in the ageing population. Recent works have suggested that circadian rhythms disruption is a common event in PD patients. Clock genes regulate the circadian rhythm of biological processes in eukaryotic organisms, but their roles in PD remain unclear. Despite this, several lines of evidence point to the possibility that clock genes may have a significant impact on the development and progression of the disease. This review aims to consolidate recent understanding of the roles of clock genes in PD. We first summarized the findings of clock gene expression and epigenetic analyses in PD patients and animal models. We also discussed the potential contributory role of clock gene variants in the development of PD and/or its symptoms. We further reviewed the mechanisms by which clock genes affect mitochondrial dynamics as well as the rhythmic synthesis and secretion of endocrine hormones, the impairment of which may contribute to the development of PD. Finally, we discussed the limitations of the currently available studies, and suggested future potential studies to deepen our understanding of the roles of clock genes in PD pathogenesis.

Matched MeSH terms: Circadian Rhythm/genetics
Fulltext Increased yield performance of mutation induced Soybean genotypes at varied agro-ecological conditions

Bhuiyan MSH, Malek MA, Emon RM, Khatun MK, Khandaker MM, Alam MA

Braz J Biol, 2022;84:e255235.
PMID: 35019108 DOI: 10.1590/1519-6984.255235

In soybean breeding program, continuous selection pressure on traits response to yield created a genetic bottleneck for improvements of soybean through hybridization breeding technique. Therefore an initiative was taken to developed high yielding soybean variety applying mutation breeding techniques at Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture (BINA), Bangladesh. Locally available popular cultivar BARI Soybean-5 was used as a parent material and subjected to five different doses of Gamma ray using Co60. In respect to seed yield and yield attributing characters, twelve true breed mutants were selected from M4 generation. High values of heritability and genetic advance with high genotypic coefficient of variance (GCV) for plant height, branch number and pod number were considered as favorable attributes for soybean improvement that ensure expected yield. The mutant SBM-18 obtained from 250Gy provided stable yield performance at diversified environments. It provided maximum seed yield of 3056 kg ha-1 with highest number of pods plant-1 (56). The National Seed Board of Bangladesh (NSB) eventually approved SBM-18 and registered it as a new soybean variety named 'Binasoybean-5' for large-scale planting because of its superior stability in various agro-ecological zones and consistent yield performance.

Matched MeSH terms: Mutation/genetics
Role of circular RNAs in determining the fate of mesenchymal stem cells

Wong RSY, Cheong SK

Malays J Pathol, 2021 Aug;43(2):241-250.
PMID: 34448788

Ribonucleic acid (RNA) has been well-understood for its linear form for many years. With advances in high-throughput sequencing, there is an increasing focus on circular RNAs (circRNAs) recently. Although they were previously regarded as splicing error by-products, research has shown that they play a pivotal role in many cellular processes, one of which is the control of stem cell differentiation and fate. On the other hand, decades of research have demonstrated the promising therapeutic potential of mesenchymal stem cells (MSCs). To this end, there is a growing body of research on the role of circRNAs in the determination of the fate of MSCs. This review critically examines the current evidence and consolidates key findings from studies that explore the involvement of circRNAs in the regulation of MSC differentiation.

Matched MeSH terms: RNA/genetics
Plasma miR-146a and miR-365 expression and inflammatory factors in patients with osteoarthritis

Wu W, Xuan Y, Ge Y, Mu S, Hu C, Fan R

Malays J Pathol, 2021 Aug;43(2):311-317.
PMID: 34448795

OBJECTIVE: To investigate the expression levels of micro-ribonucleic acid (miR)-146a and miR-365 in the plasma of osteoarthritis (OA) patients, to study their expression with the inflammatory factors and the severity of disease in patients and to analyse their diagnostic significance.
MATERIALS AND METHODS: A total of 42 OA patients diagnosed with OA and treated in our hospital from January 2017 to January 2018 were selected as the subjects, and 28 healthy people were enrolled as controls. The expressions of interleukin-1 beta (IL-1β) and IL-6 in the plasma of OA patients were detected via immunohistochemical staining. Moreover, the knee joint function of OA patients was evaluated by Lysholm score, Western Ontario and McMaster Universities (WOMAC) score and Visual Analogue Scale (VAS) score. The expression levels of plasma miR-146a and miR-365 in OA patients were measured through RT-PCR. Besides, the significance of the expression levels of miR-146a and miR-365 for the diagnosis of OA was analysed by ROC curves.
RESULTS: As compared with healthy people, OA patients had elevated expression levels of plasma IL-1β and IL-6, decreased Lysholm score, increased WOMAC and VAS scores as well as significantly up-regulated levels of plasma miR-146a and miR-365, which were of important significance for diagnosis.
CONCLUSION: The expression levels of plasma miR-146a, miR-365 and inflammatory factors are notably higher, the disease is more severe, and the function of knee joint movement is weaker in OA patients than those in healthy controls. It can be concluded that the levels of both miR-146a and miR-365 can serve as biomarkers of OA diagnosis.

Matched MeSH terms: MicroRNAs/genetics*
Chromosome-level genome sequence of the Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) highlights regions of introgression with O. mossambicus

Etherington GJ, Nash W, Ciezarek A, Mehta TK, Barria A, Peñaloza C, et al.

BMC Genomics, 2022 Dec 15;23(1):832.
PMID: 36522771 DOI: 10.1186/s12864-022-09065-8

BACKGROUND: The Nile tilapia (Oreochromis niloticus) is the third most important freshwater fish for aquaculture. Its success is directly linked to continuous breeding efforts focusing on production traits such as growth rate and weight. Among those elite strains, the Genetically Improved Farmed Tilapia (GIFT) programme initiated by WorldFish is now distributed worldwide. To accelerate the development of the GIFT strain through genomic selection, a high-quality reference genome is necessary.
RESULTS: Using a combination of short (10X Genomics) and long read (PacBio HiFi, PacBio CLR) sequencing and a genetic map for the GIFT strain, we generated a chromosome level genome assembly for the GIFT. Using genomes of two closely related species (O. mossambicus, O. aureus), we characterised the extent of introgression between these species and O. niloticus that has occurred during the breeding process. Over 11 Mb of O. mossambicus genomic material could be identified within the GIFT genome, including genes associated with immunity but also with traits of interest such as growth rate.
CONCLUSION: Because of the breeding history of elite strains, current reference genomes might not be the most suitable to support further studies into the GIFT strain. We generated a chromosome level assembly of the GIFT strain, characterising its mixed origins, and the potential contributions of introgressed regions to selected traits.

Matched MeSH terms: Chromosomes/genetics
Microcystin production by oscillatorialean cyanobacteria isolated from cryopreserved Antarctic mats

Usman AS, Merican F, Zaki S, Broady P, Convey P, Muangmai N

Harmful Algae, 2022 Dec;120:102336.
PMID: 36470600 DOI: 10.1016/j.hal.2022.102336

Twenty cyanobacterial strains of eight morphospecies isolated from deep-frozen (-15 °C) mat samples originally collected on Ross Island, in Victoria Land, and on the McMurdo Ice Shelf were screened for the presence of genes encoding for production of anatoxins, cylindrospermopsin, microcystin/nodularin and saxitoxin. One strain of each of Microcoleus autumnalis and Phormidesmis priestleyi and two strains of Wilmottia murrayi were found to produce microcystin. No toxin production was detected in the other 16 strains representing five species. The four toxin-producing strains were characterised using both morphological and molecular approaches. Phylogenetic analyses using partial 16S rRNA sequences were consistent with the morphological identification of all four strains. They were all found to contain a fragment of the mcyE gene, which is involved in microcystin biosynthesis. ELISA analysis of extracts from cultures of these strains confirmed the presence of low concentrations of microcystin: 0.35 μg/L in M. autumnalis, <0.15 μg/L in P. priestleyi, 1.60 μg/L in W. murrayi strain 1 and 0.9 μg/L in W. murrayi strain 2. This study includes the first report of microcystin synthesis by W. murrayi.

Matched MeSH terms: RNA, Ribosomal, 16S/genetics
Macrophage polarization in THP-1 cell line and primary monocytes: A systematic review

Mohd Yasin ZN, Mohd Idrus FN, Hoe CH, Yvonne-Tee GB

Differentiation, 2022;128:67-82.
PMID: 36370526 DOI: 10.1016/j.diff.2022.10.001

Macrophages derived from human monocytic leukemia THP-1 cell line are often used as the alternative of human primary macrophage. However, the polarization method of THP-1 to macrophages varies between different laboratories, which may unknowingly affect the relevance of research output across research groups. In this regard, a systematic search was developed in Pubmed, BioOne, Scopus, and Science Direct to identify articles focusing on THP-1 polarization into M1 and M2 macrophages. All selected articles were read and discussed by two independent reviewers. The selection process was based on selected keywords on the title, abstract and full-text level. A total of 85 articles were selected and categorized based on the field of studies, method of THP-1 differentiation, and markers or genes expressed upon differentiation. THP-1 derived macrophages were mainly used together with primary monocyte-derived macrophages in cellular inflammation studies, while it was commonly employed alone in cancer research. THP-1 derived macrophages are also of paramount importance in biomaterials studies to prevent unfavorable immune responses in-vivo. We explored various methods of THP-1 differentiation and suggested several common genes encountered to characterize M1 and M2 macrophages differentiated from THP-1. The systematic review highlights the relevance of using THP-1 derived macrophage as a useful alternative to primary macrophage. Although it is not possible to derive a standard method of THP-1 polarization into M1 and M2 macrophages from this review, it may lead researchers to obtain reproducible polarization protocol based on commonly used stimulants and markers of differentiation.

Matched MeSH terms: Cell Differentiation/genetics
Fulltext Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2

Salleh MZ, Norazmi MN, Deris ZZ

PeerJ, 2022;10:e13083.
PMID: 35287350 DOI: 10.7717/peerj.13083

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer protection against the disease. mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. In this review, we summarize the currently available vaccines against SARS-CoV-2 in development, with the focus on the concepts of mRNA vaccines, their antigen selection, delivery and optimization to increase the immunostimulatory capability of mRNA as well as its stability and translatability. We also discuss the host immune responses to the SARS-CoV-2 infection and expound in detail, the adaptive immune response upon immunization with mRNA vaccines, in which high levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. mRNA vaccines have been shown to induce a robust CD8+T cell response, with a balanced CD4+ TH1/TH2 response. We further discuss the challenges and limitations of COVID-19 mRNA vaccines, where newly emerging variants of SARS-CoV-2 may render currently deployed vaccines less effective. Imbalanced and inappropriate inflammatory responses, resulting from hyper-activation of pro-inflammatory cytokines, which may lead to vaccine-associated enhanced respiratory disease (VAERD) and rare cases of myocarditis and pericarditis also are discussed.

Matched MeSH terms: RNA, Messenger/genetics
An enzyme-free turn-on fluorescent strategy for nucleic acid detection based on hybridization chain reaction and transferable silver nanoclusters

Wong ZW, New SY

Mikrochim Acta, 2022 Dec 08;190(1):16.
PMID: 36480078 DOI: 10.1007/s00604-022-05591-0

A fluorescence biosensor has been developed based on hybridisation chain reaction (HCR) amplification coupled with silver nanoclusters (AgNCs) for nucleic acid detection. The fluorescence was activated via end-to-end transfer of dark AgNCs caged within a DNA template to another DNA sequence that could enhance their red fluorescence emission at 611 nm. Such cluster-transfer approach allows us to introduce fluorogenic AgNCs as external signal transducers, thereby enabling HCR to perform in a predictable manner. The resulted HCR-AgNC biosensor was able to detect target DNA with a detection limit of 3.35 fM, and distinguish the DNA target from single-base mismatch sequences. Moreover, the bright red fluorescence emission was detectable with the naked eye, with concentration of target DNA down to 1 pM. The biosensor also performed well in human serum samples with good recovery. Overall, our cluster-transfer approach provides a good alternative to construct HCR-AgNC assay with less risk of circuit leakage and produce AgNCs in a controllable manner.

Matched MeSH terms: DNA/genetics
Abstracts of the Medical Genetics Conference Kuala Lumpur 2022: The Future is Now: Challenges and Innovative Solutions in Genetic Diagnostics, co-organised by Medical Genetics Society of Malaysia, Chapter of Medical Genetic Pathology, College of Pathologists, Academy of Medicine of Malaysia and Pantai Premier Pathology and held on 7th - 9th September 2022

Malays J Pathol, 2022 Dec;44(3):539-562.
PMID: 36591723

No abstract available.

Matched MeSH terms: Genetics, Medical*
Fulltext Identification of non-ribosomal peptide synthetase in Ganoderma boninense Pat. that was expressed during the interaction with oil palm

Shokrollahi N, Ho CL, Zainudin NAIM, Wahab MABA, Wong MY

Sci Rep, 2021 Aug 11;11(1):16330.
PMID: 34381084 DOI: 10.1038/s41598-021-95549-8

Basal stem rot (BSR) of oil palm is a disastrous disease caused by a white-rot fungus Ganoderma boninense Pat. Non-ribosomal peptides (NRPs) synthesized by non-ribosomal peptide synthetases (NRPSs) are a group of secondary metabolites that act as fungal virulent factors during pathogenesis in the host. In this study, we aimed to isolate NRPS gene of G. boninense strain UPMGB001 and investigate the role of this gene during G. boninense-oil palm interaction. The isolated NRPS DNA fragment of 8322 bp was used to predict the putative peptide sequence of different domains and showed similarity with G. sinense (85%) at conserved motifs of three main NRPS domains. Phylogenetic analysis of NRPS peptide sequences demonstrated that NRPS of G. boninense belongs to the type VI siderophore family. The roots of 6-month-old oil palm seedlings were artificially inoculated for studying NRPS gene expression and disease severity in the greenhouse. The correlation between high disease severity (50%) and high expression (67-fold) of G. boninense NRPS gene at 4 months after inoculation and above indicated that this gene played a significant role in the advancement of BSR disease. Overall, these findings increase our knowledge on the gene structure of NRPS in G. boninense and its involvement in BSR pathogenesis as an effector gene.

Matched MeSH terms: Peptide Synthases/genetics*; Plant Proteins/genetics*; Genes, Plant/genetics; Plant Roots/genetics; DNA, Plant/genetics; Ganoderma/genetics*; Seedlings/genetics
Fulltext Candida khanbhai sp. nov., a new clinically relevant yeast within the Candida haemulonii species complex

de Jong AW, Al-Obaid K, Mohd Tap R, Gerrits van den Ende B, Groenewald M, Joseph L, et al.

Med Mycol, 2023 Feb 03;61(2).
PMID: 36694950 DOI: 10.1093/mmy/myad009

Invasive fungal infections caused by non-albicans Candida species are increasingly reported. Recent advances in diagnostic and molecular tools enabled better identification and detection of emerging pathogenic yeasts. The Candida haemulonii species complex accommodates several rare and recently described pathogenic species, C. duobushaemulonii, C. pseudohaemulonii, C. vulturna, and the most notorious example is the outbreak-causing multi-drug resistant member C. auris. Here, we describe a new clinically relevant yeast isolated from geographically distinct regions, representing the proposed novel species C. khanbhai, a member of the C. haemulonii species complex. Moreover, several members of the C. haemulonii species complex were observed to be invalidly described, including the clinically relevant species C. auris and C. vulturna. Hence, the opportunity was taken to correct this here, formally validating the names of C. auris, C. chanthaburiensis, C. konsanensis, C. metrosideri, C. ohialehuae, and C. vulturna.

Matched MeSH terms: Candida/genetics
Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

Adams D, Tournev IL, Taylor MS, Coelho T, Planté-Bordeneuve V, Berk JL, et al.

Amyloid, 2023 Mar;30(1):1-9.
PMID: 35875890 DOI: 10.1080/13506129.2022.2091985

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy.
METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months.
RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths.
CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.
CLINICALTRIALS.GOV: NCT03759379.

Matched MeSH terms: Prealbumin/genetics
Fulltext Integrase deficient lentiviral vector: prospects for safe clinical applications

Yew CT, Gurumoorthy N, Nordin F, Tye GJ, Wan Kamarul Zaman WS, Tan JJ, et al.

PeerJ, 2022;10:e13704.
PMID: 35979475 DOI: 10.7717/peerj.13704

HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector's replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.

Matched MeSH terms: Genetic Vectors/genetics
Fulltext Alternative antiviral approaches to combat influenza A virus

Wong KH, Lal SK

Virus Genes, 2023 Feb;59(1):25-35.
PMID: 36260242 DOI: 10.1007/s11262-022-01935-3

Influenza A (IAV) is a major human respiratory pathogen that contributes to a significant threat to health security, worldwide. Despite vaccinations and previous immunisations through infections, humans can still be infected with influenza several times throughout their lives. This phenomenon is attributed to the antigenic changes of hemagglutinin (HA) and neuraminidase (NA) proteins in IAV via genetic mutation and reassortment, conferring antigenic drift and antigenic shift, respectively. Numerous findings indicate that slow antigenic drift and reassortment-derived antigenic shift exhibited by IAV are key processes that allow IAVs to overcome the previously acquired host immunity, which eventually leads to the annual re-emergence of seasonal influenza and even pandemic influenza, in rare occasions. As a result, current therapeutic options hit a brick wall quickly. As IAV remains a constant threat for new outbreaks worldwide, the underlying processes of genetic changes and alternative antiviral approaches for IAV should be further explored to improve disease management. In the light of the above, this review discusses the characteristics and mechanisms of mutations and reassortments that contribute to IAV's evolution. We also discuss several alternative RNA-targeting antiviral approaches, namely the CRISPR/Cas13 systems, RNA interference (RNAi), and antisense oligonucleotides (ASO) as potential antiviral approaches against IAV.

Matched MeSH terms: Hemagglutinin Glycoproteins, Influenza Virus/genetics
Human monkeypox outbreak in 2022

Kumar S, Subramaniam G, Karuppanan K

J Med Virol, 2023 Jan;95(1):e27894.
PMID: 35637363 DOI: 10.1002/jmv.27894
Matched MeSH terms: Monkeypox virus/genetics

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