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Genes Jun 2024The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in...
The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role in regulating chicken adipogenesis has not been reported. In this study, the function of in chicken abdominal preadipocytes was investigated. is significantly upregulated during abdominal adipocyte differentiation. The overexpression of upregulated the expression of adipogenic marker genes and proliferation-related genes, and promoted the proliferation of adipocytes and the accumulation of triglycerides. The knockdown of downregulated the expression of adipogenic marker genes and proliferation-related genes, inhibited the proliferation of adipocytes, and impaired the accumulation of triglycerides in adipocytes. In addition, was differentially expressed in abdominal preadipocytes and mature adipocytes, and was significantly positively correlated with the expression of . Interference with inhibits the expression of adipogenic marker genes and proliferation-related genes. The data supported the notion that promotes the differentiation of chicken abdominal adipocytes by cis-regulating the expression of . This study identified the role of in the differentiation and proliferation of chicken adipocytes, providing a potential target for improving abdominal adipogenesis in chickens.
Topics: Animals; Adipocytes; Chickens; Adipogenesis; RNA, Long Noncoding; Cell Differentiation; Cell Proliferation
PubMed: 38927694
DOI: 10.3390/genes15060758 -
Biomolecules May 2024Chronic myeloid leukemia (CML) is an oncological myeloproliferative disorder that accounts for 15 to 20% of all adult leukemia cases. The molecular basis of this disease... (Review)
Review
Chronic myeloid leukemia (CML) is an oncological myeloproliferative disorder that accounts for 15 to 20% of all adult leukemia cases. The molecular basis of this disease lies in the formation of a chimeric oncogene BCR-ABL1. The protein product of this gene, p210 BCR-ABL1, exhibits abnormally high constitutive tyrosine kinase activity. Over recent decades, several targeted tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1 have been developed and introduced into clinical practice. These inhibitors suppress BCR-ABL1 activity through various mechanisms. Furthermore, the advent of RNA interference technology has enabled the highly specific inhibition of BCR-ABL1 transcript expression using small interfering RNA (siRNA). This experimental evidence opens avenues for the development of a novel therapeutic strategy for CML, termed siRNA therapy. The review delves into molecular genetic mechanisms underlying the pathogenesis of CML, challenges in CML therapy, potential molecular targets for drug development, and the latest results from the application of siRNAs in in vitro and in vivo CML models.
Topics: Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Humans; RNA, Small Interfering; Fusion Proteins, bcr-abl; Molecular Targeted Therapy; Animals; Protein Kinase Inhibitors; RNA Interference
PubMed: 38927048
DOI: 10.3390/biom14060644 -
Nature Communications Jun 2024Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the... (Comparative Study)
Comparative Study
Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.
Topics: Polysaccharides; Nanoparticles; Animals; Humans; Mice; Gene Transfer Techniques; RNAi Therapeutics; RNA Interference; Male; RNA, Small Interfering; Mice, Inbred C57BL; Myocardial Reperfusion Injury
PubMed: 38926348
DOI: 10.1038/s41467-024-49804-x -
Life Science Alliance Sep 2024In , inter-cellular transport of the small non-coding RNA causing systemic RNAi is mediated by the transmembrane protein SID1, encoded by the gene in the systemic RNAi...
In , inter-cellular transport of the small non-coding RNA causing systemic RNAi is mediated by the transmembrane protein SID1, encoded by the gene in the systemic RNAi defective () loci. SID1 shares structural and sequence similarity with cholesterol uptake protein 1 (CHUP1) and is classified as a member of the ChUP family. Although systemic RNAi is not an evolutionarily conserved process, the gene products are found across the animal kingdom, suggesting the existence of other novel gene regulatory mechanisms mediated by small non-coding RNAs. Human homologs of gene products-hSIDT1 and hSIDT2-mediate contact-dependent lipophilic small non-coding dsRNA transport. Here, we report the structure of recombinant human SIDT1. We find that the extra-cytosolic domain of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain exists as two modules-a flexible lipid binding domain and a rigid transmembrane domain core. Our structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in ChUP family members.
Topics: Humans; Membrane Proteins; Protein Binding; Protein Domains; Models, Molecular; Protein Conformation; Caenorhabditis elegans; Animals; Amino Acid Sequence; Binding Sites; Lipids; Caenorhabditis elegans Proteins; RNA Interference
PubMed: 38925866
DOI: 10.26508/lsa.202402624 -
Metabolites Jun 2024The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and... (Review)
Review
The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.
PubMed: 38921477
DOI: 10.3390/metabo14060343 -
Insects Jun 2024iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the...
iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the insect iGABAR. However, little information about GRD in has been reported. In this study, we involved cloning and characterizing the iGABAR subunit of (). Sequence analysis indicated that , as part of the cysteine-loop ligand-gated ion channel family, is similar to other insect . RNA interference (RNAi) was employed to explore IVM resistance in , resulting in a significant reduction in expression ( < 0.05), and the mortality of adults with knockdown was significantly decreased after exposure to ivermectin. Bioinformatics prediction identified miR-71-5p as a potential regulator of . In vitro, dual-luciferase reporter assays confirmed that expression was regulated by miR-71-5p. Microinjection of miR-71-5p mimics upregulated miR-71-5p expression and downregulated gene expression, reducing mortality by 34.52% following IVM treatment. Conversely, microinjection of a miR-71-5p inhibitor decreased miR-71-5p expression but did not affect the susceptibility to IVM despite increased expression ( < 0.05). In conclusion, , as one of the iGABA receptor subunits, is a potential target of ivermectin. It may influence ivermectin resistance by modulating the GABA signaling pathway. The inhibition of expression by miR-71-5p decreased ivermectin resistance and consequently lowered the mortality rate of mosquitoes. This finding provides empirical evidence of the relationship between and its miRNA in modulating insecticide resistance, offering novel perspectives for mosquito control strategies.
PubMed: 38921167
DOI: 10.3390/insects15060453 -
Insects May 2024Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the...
Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; , Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.
PubMed: 38921109
DOI: 10.3390/insects15060394 -
Insects May 2024(Acari: Tetranychidae) has caused serious economic losses on some crops (soybean, corn, and cotton) in China, and has developed resistance to most acaricides. Our...
Differential Antioxidant Enzyme Gene Expression and Functional Analysis of Pyridaben-Susceptible and -Resistant Strains of (Acari: Tetranychidae) under High Temperature Stress.
(Acari: Tetranychidae) has caused serious economic losses on some crops (soybean, corn, and cotton) in China, and has developed resistance to most acaricides. Our laboratory study found that was resistant to pyridaben and also adapted to high temperature (34-40 °C). High temperature stress may cause arthropods to produce a large amount of reactive oxygen species (ROS), causing oxidative damage. Antioxidant enzymes, as the main antioxidants, can reduce the damage caused by excessive ROS in arthropods. In order to study the adaptation mechanism of the pyridaben-resistant strain of to high temperature and the role of antioxidant enzyme genes under high temperature stress, four antioxidant enzyme genes, , , , and , were screened according to the transcriptome sequencing data of pyridaben-susceptible and -resistant strains in . Firstly, the phylogeny and structure analyses of these four genes were carried out. Then, real-time quantitative PCR (RT-qPCR) technology was used to analyze the gene expression patterns of antioxidant enzymes in two strains of at three different high temperature ranges (34 °C, 38 °C, and 42 °C). The results showed that the expression levels of four antioxidant enzyme genes of two strains of were induced by high temperature stress, and the expression levels of antioxidant enzyme genes were significantly different in each development state. The gene expression of antioxidant enzyme genes in resistant strains at the adult stage was significantly higher than that in susceptible strains. After the and genes of adult mites of the resistant strain were silenced by RNA interference (RNAi) technology, the mortality rate of mites with gene silencing reached 41.11% after 96 h at 34 °C, which was significantly higher than that of the control and gene silencing. It has been confirmed that the gene plays a key role in the adaptation of pyridaben-resistant strain of to high temperature. It lays a theoretical foundation for revealing the thermal adaptation mechanism of .
PubMed: 38921096
DOI: 10.3390/insects15060381 -
Insects May 2024RNA interference inhibitors were initially discovered in plant viruses, representing a unique mechanism employed by these viruses to counteract host RNA interference....
RNA interference inhibitors were initially discovered in plant viruses, representing a unique mechanism employed by these viruses to counteract host RNA interference. This mechanism has found extensive applications in plant disease resistance breeding and other fields; however, the impact of such interference inhibitors on insect cell RNA interference remains largely unknown. In this study, we screened three distinct interference inhibitors from plant and mammal viruses that act through different mechanisms and systematically investigated their effects on the insect cell cycle and baculovirus infection period at various time intervals. Our findings demonstrated that the viral suppressors of RNA silencing (VSRs) derived from plant and mammal viruses significantly attenuated the RNA interference effect in insect cells, as evidenced by reduced apoptosis rates, altered gene regulation patterns in cells, enhanced expression of exogenous proteins, and improved production efficiency of recombinant virus progeny. Further investigations revealed that the early expression of VSRs yielded superior results compared with late expression during RNA interference processes. Additionally, our results indicated that dsRNA-binding inhibition exhibited more pronounced effects than other modes of action employed by these interference inhibitors. The outcomes presented herein provide novel insights into enhancing defense mechanisms within insect cells using plant and mammal single-stranded RNA virus-derived interference inhibitors and have potential implications for expanding the scope of transformation within insect cell expression systems.
PubMed: 38921090
DOI: 10.3390/insects15060375 -
Cureus Jun 2024Cardiovascular diseases are the leading causes of global mortality and morbidity. Hyperlipidemia is a significant risk factor for atherosclerosis and subsequent... (Review)
Review
Cardiovascular diseases are the leading causes of global mortality and morbidity. Hyperlipidemia is a significant risk factor for atherosclerosis and subsequent cardiovascular diseases. Hyperlipidemia is characterized by imbalances in blood cholesterol levels, particularly elevated low-density lipoprotein cholesterol and triglycerides, and is influenced by genetic and environmental factors. Current management consists of lifestyle modifications and pharmacological interventions most commonly consisting of statins. This review paper explores pathophysiology, management strategies, and pharmacotherapies including commonly used well-established medications including statins, fibrates, and ezetimibe, exciting novel therapies including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and RNA interference therapies (inclisiran), lomitapide, and bempedoic acid, highlighting their mechanisms of action, clinical efficacy, and safety profiles. Additionally, emerging therapies under clinical trials including ApoC-III inhibitors, DGAT2 inhibitors, ACAT2 Inhibitors, and LPL gene therapies are examined for their potential to improve lipid homeostasis and cardiovascular outcomes. The evolving landscape of hyperlipidemia management underscores the importance of continued research into both established therapies and promising new candidates, offering hope for more effective treatment strategies in the future.
PubMed: 38919858
DOI: 10.7759/cureus.63078