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1.
Mol Cell ; 83(8): 1280-1297.e11, 2023 04 20.
Article in English | MEDLINE | ID: mdl-36924766

ABSTRACT

RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chromatography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS)," we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 3' end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to increase the efficiency of 3' end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disassociated subunits in mammalian cells.


Subject(s)
RNA Polymerase II , Transcription, Genetic , Animals , RNA Polymerase II/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Ribosomes/metabolism , Protein Subunits/genetics , Mammals/metabolism
2.
RNA ; 30(5): 537-547, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38531648

ABSTRACT

Over the past decade, advancements in epitranscriptomics have significantly enhanced our understanding of mRNA metabolism and its role in human development and diseases. This period has witnessed breakthroughs in sequencing technologies and the identification of key proteins involved in RNA modification processes. Alongside the well-studied m6A, Ψ and m1A have emerged as key epitranscriptomic markers. Initially identified through transcriptome-wide profiling, these modifications are now recognized for their broad impact on RNA metabolism and gene expression. In this Perspective, we focus on the detections and functions of Ψ and m1A modifications in mRNA and discuss previous discrepancies and future challenges. We summarize recent advances and highlight the latest sequencing technologies for stoichiometric detection and their mechanistic investigations for functional unveiling in mRNA as the new research directions.


Subject(s)
RNA Processing, Post-Transcriptional , Transcriptome , Humans , RNA, Messenger/genetics , High-Throughput Nucleotide Sequencing , Gene Expression Profiling , RNA
3.
Plant Cell ; 34(11): 4232-4254, 2022 10 27.
Article in English | MEDLINE | ID: mdl-36047828

ABSTRACT

Maternal-to-filial nutrition transfer is central to grain development and yield. nitrate transporter 1/peptide transporter (NRT1-PTR)-type transporters typically transport nitrate, peptides, and ions. Here, we report the identification of a maize (Zea mays) NRT1-PTR-type transporter that transports sucrose and glucose. The activity of this sugar transporter, named Sucrose and Glucose Carrier 1 (SUGCAR1), was systematically verified by tracer-labeled sugar uptake and serial electrophysiological studies including two-electrode voltage-clamp, non-invasive microelectrode ion flux estimation assays in Xenopus laevis oocytes and patch clamping in HEK293T cells. ZmSUGCAR1 is specifically expressed in the basal endosperm transfer layer and loss-of-function mutation of ZmSUGCAR1 caused significantly decreased sucrose and glucose contents and subsequent shrinkage of maize kernels. Notably, the ZmSUGCAR1 orthologs SbSUGCAR1 (from Sorghum bicolor) and TaSUGCAR1 (from Triticum aestivum) displayed similar sugar transport activities in oocytes, supporting the functional conservation of SUGCAR1 in closely related cereal species. Thus, the discovery of ZmSUGCAR1 uncovers a type of sugar transporter essential for grain development and opens potential avenues for genetic improvement of seed-filling and yield in maize and other grain crops.


Subject(s)
Edible Grain , Glucose , Nitrate Transporters , Peptide Transporter 1 , Plant Proteins , Sucrose , Zea mays , Humans , Edible Grain/genetics , Edible Grain/growth & development , Glucose/metabolism , HEK293 Cells , Nitrate Transporters/genetics , Nitrate Transporters/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Sucrose/metabolism , Zea mays/growth & development , Zea mays/metabolism , Peptide Transporter 1/genetics , Peptide Transporter 1/metabolism , Biological Transport
4.
Nat Chem Biol ; 19(10): 1185-1195, 2023 10.
Article in English | MEDLINE | ID: mdl-36997645

ABSTRACT

Pseudouridine (Ψ) is an abundant post-transcriptional RNA modification in ncRNA and mRNA. However, stoichiometric measurement of individual Ψ sites in human transcriptome remains unaddressed. Here we develop 'PRAISE', via selective chemical labeling of Ψ by bisulfite to induce nucleotide deletion signature during reverse transcription, to realize quantitative assessment of the Ψ landscape in the human transcriptome. Unlike traditional bisulfite treatment, our approach is based on quaternary base mapping and revealed an ~10% median modification level for 2,209 confident Ψ sites in HEK293T cells. By perturbing pseudouridine synthases, we obtained differential mRNA targets of PUS1, PUS7, TRUB1 and DKC1, with TRUB1 targets showing the highest modification stoichiometry. In addition, we quantified known and new Ψ sites in mitochondrial mRNA catalyzed by PUS1. Collectively, we provide a sensitive and convenient method to measure transcriptome-wide Ψ; we envision this quantitative approach would facilitate emerging efforts to elucidate the function and mechanism of mRNA pseudouridylation.


Subject(s)
Sulfites , Transcriptome , Humans , HEK293 Cells , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA Processing, Post-Transcriptional , Pseudouridine/genetics , Pseudouridine/metabolism , Nuclear Proteins/genetics , Cell Cycle Proteins/genetics
5.
Mol Cell ; 68(5): 993-1005.e9, 2017 Dec 07.
Article in English | MEDLINE | ID: mdl-29107537

ABSTRACT

Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.


Subject(s)
Adenosine/analogs & derivatives , Cell Nucleus/metabolism , Mitochondria/metabolism , RNA Processing, Post-Transcriptional , RNA, Messenger/metabolism , RNA, Transfer/metabolism , Single Molecule Imaging/methods , 5' Untranslated Regions , Adenosine/metabolism , HEK293 Cells , Humans , Mitochondrial Proteins/biosynthesis , Mitochondrial Proteins/genetics , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Protein Biosynthesis , RNA Caps , RNA Interference , RNA, Messenger/genetics , RNA, Transfer/genetics , Transfection , tRNA Methyltransferases/genetics , tRNA Methyltransferases/metabolism
6.
Am J Physiol Cell Physiol ; 327(3): C737-C749, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39069827

ABSTRACT

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.


Subject(s)
Citric Acid , Diet, High-Fat , Zebrafish , Animals , Diet, High-Fat/adverse effects , Citric Acid/metabolism , Metabolic Syndrome/metabolism , Metabolic Syndrome/prevention & control , Metabolic Syndrome/genetics , Metabolic Syndrome/etiology , Mitochondria/metabolism , Mitochondria/drug effects , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Obesity/metabolism , Obesity/prevention & control , Obesity/genetics , Obesity/etiology , Acetylation , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Liver/metabolism , Liver/drug effects , Liver/pathology , Male , Insulin Resistance , Fatty Liver/metabolism , Fatty Liver/prevention & control , Fatty Liver/pathology , Fatty Liver/etiology , Lipid Metabolism/drug effects
7.
J Biol Chem ; 299(10): 105220, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37660921

ABSTRACT

Pharmacological inhibition of mitochondrial fatty acid oxidation (FAO) has been clinically used to alleviate certain metabolic diseases by remodeling cellular metabolism. However, mitochondrial FAO inhibition also leads to mechanistic target of rapamycin complex 1 (mTORC1) activation-related protein synthesis and tissue hypertrophy, but the mechanism remains unclear. Here, by using a mitochondrial FAO inhibitor (mildronate or etomoxir) or knocking out carnitine palmitoyltransferase-1, we revealed that mitochondrial FAO inhibition activated the mTORC1 pathway through general control nondepressible 5-dependent Raptor acetylation. Mitochondrial FAO inhibition significantly promoted glucose catabolism and increased intracellular acetyl-CoA levels. In response to the increased intracellular acetyl-CoA, acetyltransferase general control nondepressible 5 activated mTORC1 by catalyzing Raptor acetylation through direct interaction. Further investigation also screened Raptor deacetylase histone deacetylase class II and identified histone deacetylase 7 as a potential regulator of Raptor. These results provide a possible mechanistic explanation for the mTORC1 activation after mitochondrial FAO inhibition and also bring light to reveal the roles of nutrient metabolic remodeling in regulating protein acetylation by affecting acetyl-CoA production.

8.
BMC Plant Biol ; 24(1): 532, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38862892

ABSTRACT

BACKGROUND: Mung bean (Vigna radiata L.) is an important warm-season grain legume. Adaptation to extreme environmental conditions, supported by evolution, makes mung bean a rich gene pool for stress tolerance traits. The exploration of resistance genes will provide important genetic resources and a theoretical basis for strengthening mung bean breeding. B-box (BBX) proteins play a major role in developmental processes and stress responses. However, the identification and analysis of the mung bean BBX gene family are still lacking. RESULTS: In this study, 23 VrBBX genes were identified through comprehensive bioinformatics analysis and named based on their physical locations on chromosomes. All the VrBBXs were divided into five groups based on their phylogenetic relationships, the number of B-box they contained and whether there was an additional CONSTANS, CO-like and TOC1 (CCT) domain. Homology and collinearity analysis indicated that the BBX genes in mung bean and other species had undergone a relatively conservative evolution. Gene duplication analysis showed that only chromosomal segmental duplication contributed to the expansion of VrBBX genes and that most of the duplicated gene pairs experienced purifying selection pressure during evolution. Gene structure and motif analysis revealed that VrBBX genes clustered in the same group shared similar structural characteristics. An analysis of cis-acting elements indicated that elements related to stress and hormone responses were prevalent in the promoters of most VrBBXs. The RNA-seq data analysis and qRT-PCR of nine VrBBX genes demonstrated that VrBBX genes may play a role in response to environmental stress. Moreover, VrBBX5, VrBBX10 and VrBBX12 are important candidate genes for plant stress response. CONCLUSIONS: In this study, we systematically analyzed the genomic characteristics and expression patterns of the BBX gene family under ABA, PEG and NaCl treatments. The results will help us better understand the complexity of the BBX gene family and provide valuable information for future functional characteristics of specific genes in this family.


Subject(s)
Evolution, Molecular , Multigene Family , Phylogeny , Plant Proteins , Vigna , Vigna/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Genome, Plant , Gene Duplication , Stress, Physiological/genetics
9.
New Phytol ; 242(3): 1275-1288, 2024 May.
Article in English | MEDLINE | ID: mdl-38426620

ABSTRACT

Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root-soil interactions across soils with different nutrient statuses remain elusive. We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long-term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones. The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient-deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input. In conclusion, our results show that maize selects microbes at the root-soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.


Subject(s)
Alphaproteobacteria , Microbiota , Zea mays/microbiology , Soil Microbiology , Soil/chemistry , Rhizosphere , Fertilization
10.
Plant Physiol ; 191(4): 2316-2333, 2023 04 03.
Article in English | MEDLINE | ID: mdl-36652388

ABSTRACT

Carbon and nitrogen are the two main nutrients in maize (Zea mays L.) kernels, and kernel filling and metabolism determine seed formation and germination. However, the molecular mechanisms underlying the relationship between kernel filling and corresponding carbon and nitrogen metabolism remain largely unknown. Here, we found that HEAT SHOCK PROTEIN 90.6 (HSP90.6) is involved in both seed filling and the metabolism processes of carbon and nitrogen. A single-amino acid mutation within the HATPase_c domain of HSP90.6 led to small kernels. Transcriptome profiling showed that the expression of amino acid biosynthesis- and carbon metabolism-related genes was significantly downregulated in the hsp90.6 mutant. Further molecular evidence showed strong interactions between HSP90.6 and the 26S proteasome subunits REGULATORY PARTICLE NON-ATPASE6 (RPN6) and PROTEASOME BETA SUBUNITD2 (PBD2). The mutation of hsp90.6 significantly reduced the activity of the 26S proteasome, resulting in the accumulation of ubiquitinated proteins and defects in nitrogen recycling. Moreover, we verified that HSP90.6 is involved in carbon metabolism through interacting with the 14-3-3 protein GENERAL REGULATORY FACTOR14-4 (GF14-4). Collectively, our findings revealed that HSP90.6 is involved in seed filling and development by interacting with the components controlling carbon and nitrogen metabolism.


Subject(s)
Carbon , Seeds , Carbon/metabolism , Seeds/metabolism , Amino Acids/metabolism , Nitrogen/metabolism , Heat-Shock Proteins/metabolism , Zea mays/metabolism
11.
Plant Cell Environ ; 47(2): 600-610, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37885374

ABSTRACT

Ectomycorrhizal fungi (ECMFs) that are involved in phosphorus mobilisation and turnover have limited ability to mineralise phytate alone. The endofungal bacteria in the ectomycorrhizal fruiting body may contribute to achieving this ecological function of ECMFs. We investigated the synergistic effect and mechanisms of endofungal bacteria and ECMF Suillus grevillea on phytate mineralisation. The results showed that soluble phosphorus content in the combined system of endofungal bacterium Cedecea lapagei and S. grevillea was 1.8 times higher than the sum of C. lapagei and S. grevillea alone treatment under the phytate mineralisation experiment. The S. grevillea could first chemotactically assist C. lapagei in adhering to the surface of S. grevillea. Then, the mineralisation of phytate was synergistically promoted by increasing the biomass of C. lapagei and the phosphatase and phytase activities of S. grevillea. The expression of genes related to chemotaxis, colonisation, and proliferation of C. lapagei and genes related to phosphatase and phytase activity of S. grevillea was also significantly upregulated. Furthermore, in the pot experiment, we verified that there might exist a ternary symbiotic system in the natural forest in which endofungal bacteria and ECMFs could synergistically promote phytate uptake in the plant Pinus massoniana via the ectomycorrhizal system.


Subject(s)
6-Phytase , Mycorrhizae , Pinus , Mycorrhizae/metabolism , Pinus/metabolism , Phosphorus/metabolism , 6-Phytase/metabolism , Phytic Acid/metabolism , Phosphoric Monoester Hydrolases/metabolism , Bacteria/metabolism
12.
Acc Chem Res ; 56(21): 2980-2991, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37851547

ABSTRACT

Since the discovery of the first chemically modified RNA nucleotide in 1951, more than 170 types of chemical modifications have been characterized in RNA so far. Since the discovery of the reversible and dynamic nature of N6-methyladenosine (m6A) in mRNA modification, researchers have identified about ten modifications in eukaryotic mRNA; together with modifications on the noncoding RNAs, the term "epitranscriptome" has been coined to describe the ensemble of various chemical RNA modifications. The past decade has witnessed the discovery of many novel molecular functions of mRNA modifications, demonstrating their crucial roles in gene expression regulation. As the most abundant modifications in mRNA, the study of m6A and Ψ has been facilitated by innovative high-throughput sequencing technologies, which can be based on antibodies, enzymes, or novel chemistry. Among them, chemical-assisted methods utilize selective chemistry that can discriminate modified versus unmodified nucleotides, enabling the transcriptome-wide mapping of m6A and Ψ modifications and functional studies.Our group has developed several sequencing technologies to investigate these epitranscriptomic marks including m6A, Ψ, m1A, and m6Am. Among them, we have recently developed two methods for absolute quantification of m6A and Ψ in the transcriptome based on chemical reactivity to distinguish and measure the two modifications. In GLORI, we used glyoxal and nitrite to mediate efficient deamination of regular adenosine, while m6A remained unaffected, thereby enabling efficient and unbiased detection of single-base resolution and absolute quantification of m6A modification. In CeU-seq and PRAISE, we used different chemistry to achieve selective labeling and detection of transcriptome-wide Ψ. CeU-seq is based on an azido-derivatized carbodiimide compound, while PRAISE utilizes the unique activity of bisulfite to Ψ. PRAISE results in the formation of ring-opening Ψ-bisulfite adduct and quantitatively detects Ψ as 1-2 nt deletion signatures during sequencing. The resulting base-resolution and stoichiometric information expanded our understanding to the profiles of RNA modifications in the transcriptome. In particular, the quantitative information on RNA methylome is critical for characterizing the dynamic and reversible nature of RNA modifications, for instance, under environmental stress or during development. Additionally, base-resolution and stoichiometric information can greatly facilitate the analysis and characterization of functional modification sites that are important for gene expression regulation, especially when one modification type may have multiple or even opposing functions within a specific transcript. Together, the quantitative profiling methods provide the modification stoichiometry information, which is critical to study the regulatory roles of RNA modifications.In this Account, we will focus on the quantitative sequencing technologies of m6A and Ψ developed in our group, review recent advances in chemical-assisted reactions for m6A and Ψ detection, and discuss the challenges and future opportunities of transcriptome-wide mapping technologies for RNA modifications.


Subject(s)
RNA , Transcriptome , RNA/chemistry , Sulfites , RNA, Messenger , RNA Processing, Post-Transcriptional
13.
Opt Express ; 32(4): 6121-6129, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38439322

ABSTRACT

A few-mode erbium-doped waveguide amplifier (FM-EDWA) with a confined Er3+ doped ring structure is proposed to equalize the differential modal gain (DMG). The FM-EDWA amplifying three spatial modes (LP01, LP11a and LP11b) is optimized by genetic algorithm and fabricated using precise lithography overlay alignment technology. We observe gain values of over 14 dB for all modes with DMG of 0.73 dB at 1529 nm pumped only with LP01 for the power of 200 mW. Furthermore, a flat gain of more than 10 dB is demonstrated across 1525-1565 nm, with a sufficiently low DMG of less than 1.3 dB.

14.
Haemophilia ; 30(2): 276-285, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38343114

ABSTRACT

INTRODUCTION: With the increase in life expectancy of haemophilia patients (PWH), the risk of osteoporosis increases, but there is little research on whether haemophilia is the cause of osteoporosis. AIM: To conduct systematically review whether bone mineral density (BMD) in PWH decreased and the factors affecting BMD. METHODS: Two authors independently searched databases and reviewed citations from relevant articles, selecting studies published in any language and performed in humans before March 2023. Eligibility criteria were observational studies in PWH, with BMD as at least one outcome other than osteoporosis or bone loss, and analyses in a group of PWH and healthy controls. RESULTS: Twelve studies were ultimately identified, consisting of 1210 individuals (534 PWH and 676 healthy controls), compared with the control group, BMD in PWH decreased by 0.13 g/cm2 [95% confidence interval (CI) -0.18 to -0.08, I2  = 89%]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity, the types of haemophilia, haemophilia severity, a blood-borne virus (HCV) and treatment modality predicted the BMD in PWH. CONCLUSION: The results indicate that BMD in PWH is lower than in healthy controls. Therefore, we strongly recommend PWH early measurement of BMD to prevent osteoporosis.


Subject(s)
Bone Density , Hemophilia A , Humans , Hemophilia A/complications , Osteoporosis/etiology
15.
Fish Shellfish Immunol ; 150: 109598, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38697375

ABSTRACT

In mammals, IL-22 is considered as a critical cytokine regulating of immunity and homeostasis at barrier surfaces. Although IL-22 have been functional characterization in different species of fish, the studies about distinct responses of IL-22 in different organs/tissues/cell types is rather limited. Here, we identified and cloned IL-22 gene (named as Ec-IL-22) from grouper (Epinephelus coioides). Ec-IL-22 gene was detected in all orangs/tissues examined, and was induced in intestine, gill, spleen, head kidney, and primary head kidney/intestine leukocytes following the stimulation of LPS and poly (I:C), as well as Vibrio harveyi and Singapore grouper iridovirus infection (SGIV). In addition, the stimulation of DSS could induce the expression of Ec-IL-22 in intestine and primary leukocytes from intestine. Importantly, the treatment of recombinant Ec-IL-22 induced the mRNA level of proinflammatory cytokines in primary intestine/head kidney leukocytes. The present results improve the understanding of expression patterns and functional characteristics of fish IL-22 in different organs/tissues/cell types.


Subject(s)
Bass , DNA Virus Infections , Fish Diseases , Fish Proteins , Gene Expression Regulation , Interleukin-22 , Interleukins , Vibrio Infections , Vibrio , Animals , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/chemistry , Fish Diseases/immunology , Interleukins/genetics , Interleukins/immunology , Bass/immunology , Bass/genetics , Vibrio/physiology , DNA Virus Infections/immunology , DNA Virus Infections/veterinary , Gene Expression Regulation/immunology , Gene Expression Regulation/drug effects , Vibrio Infections/immunology , Vibrio Infections/veterinary , Amino Acid Sequence , Gene Expression Profiling/veterinary , Phylogeny , Sequence Alignment/veterinary , Immunity, Innate/genetics , Poly I-C/pharmacology , Lipopolysaccharides/pharmacology , Ranavirus/physiology
16.
Fish Shellfish Immunol ; 152: 109776, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39019128

ABSTRACT

Type I IFNs are a subset of cytokines exerting their antiviral effects mainly through the JAK-STAT signalling. Immunogenetic studies have shown that fish possess key components of IFN-JAK-STAT cascade, but the information about the distinct responses of STAT1 and STAT2 to different IFNs is rather limited in fish. Here, we identified and cloned STAT1 and STAT2 genes (named as On-STAT1 and On-STAT2) from tilapia, Oreochromis niloticus. On-STAT1 and On-STAT2 genes were detected in all orangs/tissues examined, and were rapidly induced in spleen, head kidney, and liver following the stimulation of poly(I:C). In addition, the stimulation of poly(I:C), poly(A:T), and different subgroups of recombinant IFNs could induce the expression of On-STAT1 and On-STAT2 in TA-02 cells with distinct induction levels. Importantly, On-STAT2 was rapidly phosphorylated by all three subgroups of IFNs, but the phosphorylation of On-STAT1 was only observed in IFNc- and IFNh-treated TA-02 cells, reflecting the distinct activation of STAT by different subgroups of fish IFNs. The present results thus contribute to better understanding of the JAK-STAT signalling mediated by different subgroups of IFNs in fish.


Subject(s)
Fish Proteins , STAT1 Transcription Factor , STAT2 Transcription Factor , Animals , STAT2 Transcription Factor/genetics , STAT2 Transcription Factor/metabolism , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , Phosphorylation , Interferon Type I/genetics , Interferon Type I/immunology , Cichlids/immunology , Cichlids/genetics , Amino Acid Sequence , Gene Expression Regulation/immunology , Gene Expression Regulation/drug effects , Phylogeny , Poly I-C/pharmacology , Sequence Alignment/veterinary , Signal Transduction/drug effects
17.
Fish Shellfish Immunol ; 153: 109852, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39173982

ABSTRACT

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1ß, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-ß. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1ß signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.


Subject(s)
Animal Feed , Cichlids , Fish Diseases , Gossypol , Pediococcus pentosaceus , Probiotics , Signal Transduction , Animals , Cichlids/immunology , Fish Diseases/immunology , Fish Diseases/chemically induced , Fish Diseases/prevention & control , Probiotics/pharmacology , Probiotics/administration & dosage , Animal Feed/analysis , Signal Transduction/drug effects , Gossypol/administration & dosage , Gossypol/pharmacology , Diet/veterinary , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Aeromonas hydrophila/physiology , NF-kappa B/metabolism , NF-kappa B/genetics , Gastrointestinal Microbiome/drug effects , Intestines/drug effects , Intestines/immunology , Inflammation/veterinary , Inflammation/chemically induced , Inflammation/immunology , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/immunology , Fish Proteins/genetics , Fish Proteins/metabolism , Fish Proteins/immunology , Enteritis/veterinary , Enteritis/prevention & control , Enteritis/chemically induced , Enteritis/immunology , Enteritis/microbiology
18.
BMC Psychiatry ; 24(1): 491, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977949

ABSTRACT

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.


Subject(s)
Antipsychotic Agents , Bipolar Disorder , Exanthema , Lurasidone Hydrochloride , Humans , Lurasidone Hydrochloride/adverse effects , Lurasidone Hydrochloride/therapeutic use , Male , Bipolar Disorder/drug therapy , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Middle Aged , Exanthema/chemically induced , East Asian People
19.
J Nanobiotechnology ; 22(1): 140, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38556857

ABSTRACT

BACKGROUND: Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. RESULTS: In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas. CONCLUSIONS: Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.


Subject(s)
Nanoparticles , Plants, Medicinal , Humans , China , Bibliometrics , Plant Extracts
20.
Lipids Health Dis ; 23(1): 268, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182089

ABSTRACT

BACKGROUND: The progression of tumours is related to abnormal phospholipid metabolism. This study is anticipated to present a fresh perspective for disease therapy targets of hepatocarcinoma caused by hepatitis B virus in the future by screening feature genes related to phospholipid metabolism. METHODS: This study analysed GSE121248 to pinpoint differentially expressed genes (DEGs). By examining the overlap between the metabolism-related genes and DEGs, the research focused on the genes involved in phospholipid metabolism. To find feature genes, functional enrichment studies were carried out and a network diagram was proposed. These findings were validated via data base of The Cancer Genome Atlas (TCGA). Further analyses included immune infiltration studies and metabolomics. Finally, the relationships between differentially abundant metabolites and feature genes were confirmed by molecular docking, providing a thorough comprehension of the molecular mechanisms. RESULTS: The seven genes with the highest degree of connection (PTGS2, IGF1, SPP1, BCHE, NR1I2, NAMPT, and FABP1) were identified as feature genes. In the TCGA database, the seven feature genes also had certain diagnostic efficiency. Immune infiltration analysis revealed that feature genes regulate the infiltration of various immune cells. Metabolomics successfully identified the different metabolites of the phospholipid metabolism pathway between patients and normal individuals. The docking study indicated that different metabolites may play essential roles in causing disease by targeting feature genes. CONCLUSIONS: In this study, for the first time, it reveals the possible involvement of genes linked to phospholipid metabolism-related genes using bioinformatics analysis. Identifying genes and probable therapeutic targets could provide clues for the further treatment of disease.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B virus , Hepatitis B , Liver Neoplasms , Molecular Docking Simulation , Phospholipids , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/virology , Liver Neoplasms/metabolism , Hepatitis B/genetics , Hepatitis B/complications , Hepatitis B/metabolism , Hepatitis B/virology , Hepatitis B virus/genetics , Phospholipids/metabolism , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Metabolomics/methods , Gene Expression Profiling
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