J Exp Bot. 2023 Mar 17:erad104. doi: 10.1093/jxb/erad104. Online ahead of print.

ABSTRACT

Somatic hybrids between distant species offer a remarkable model to study genomic recombination events after mitochondrial fusion. Recently, our lab described highly chimeric mitogenomes in two somatic hybrids between the Solanaceae Nicotiana tabacum and Hyoscyamus niger resulting from interparental homologous recombination. To better examine the recombination map in somatic hybrid mitochondria, we developed a more sensitive bioinformatic strategy to detect recombination activity based on high-throughput sequencing without assembling the hybrid mitogenome. We generated a new intergeneric somatic hybrid between N. tabacum and Physochlaina orientalis and re-analyzed the somatic hybrids previously generated in our lab. We inferred 213 homologous recombination events across repeats of 2.1 kb on average. Most of them (~80%) were asymmetrical, consistent with the break-induced replication (BIR) pathway. Only rare (2.74%) non-homologous events were detected. Interestingly, independent events frequently occurred in the same regions within and across somatic hybrids, suggesting the existence of recombination hotspots in plant mitogenomes. BIR is the main pathway of interparental recombination in somatic hybrid mitochondria. Findings of this study are relevant to mitogenome editing assays and to mechanistic aspects of DNA integration following mitochondrial DNA horizontal transfer events.

PMID:36928121 | DOI:10.1093/jxb/erad104

Genes Genet Syst. 2023 Mar 16. doi: 10.1266/ggs.22-00022. Online ahead of print.

ABSTRACT

Alzheimer's disease (AD) and major depressive disorder (MDD) are comorbid neuropsychiatric disorders that are among the leading causes of long-term disability worldwide. Recent research has indicated the existence of parallel molecular mechanisms between AD and MDD in the dorsolateral prefrontal cortex (DLPFC). However, the premorbid history and molecular mechanisms have not yet been well characterized. In this study, differentially expressed gene (DEG), differentially co-expressed gene and protein-protein interaction (PPI) network propagation analyses were applied to gene expression data of postmortem DLPFC samples from human individuals diagnosed with and without AD or MDD (AD: cases = 310, control = 157; MDD: cases = 75, control = 161) to identify the main genes in the two disorders' specific and shared biological pathways. Subsequently, the results were evaluated using another four assessment datasets (n1 = 230, n2 = 65, n3 = 58, n4 = 48). Moreover, the postmortem DLPFC methylation status of human subjects with AD or MDD was compared using 68 and 608 samples for AD and MDD, respectively. Eight genes (XIST, RPS4Y1, DDX3Y, USP9Y, DDX3X, TMSB4Y, ZFY and E1FAY) were common DEGs in DLPFC of subjects with AD or MDD. These genes play important roles in the nervous system and the innate immune system. Furthermore, we found HSPG2, DAB2IP, ARHGAP22, TXNRD1, MYO10, SDK1 and KRT82 as common differentially methylated genes in the DLPFC of cases with AD or MDD. Finally, as evidence of shared molecular mechanisms behind this comorbidity, we propose some genes as candidate biomarkers for both AD and MDD. However, more research is required to clarify the molecular mechanisms underlying the co-existence of these two important neuropsychiatric disorders.

PMID:36928034 | DOI:10.1266/ggs.22-00022

NPJ Syst Biol Appl. 2023 Mar 16;9(1):8. doi: 10.1038/s41540-023-00271-y.

ABSTRACT

Sequencing of B-cell and T-cell immune receptor repertoires helps us to understand the adaptive immune response, although it only provides information about the clonotypes (lineages) and their frequencies and not about, for example, their affinity or antigen (Ag) specificity. To further characterize the identified clones, usually with special attention to the particularly abundant ones (dominant), additional time-consuming or expensive experiments are generally required. Here, we present an extension of a multiscale model of the germinal center (GC) that we previously developed to gain more insight in B-cell repertoires. We compare the extent that these simulated repertoires deviate from experimental repertoires established from single GCs, blood, or tissue. Our simulations show that there is a limited correlation between clonal abundance and affinity and that there is large affinity variability among same-ancestor (same-clone) subclones. Our simulations suggest that low-abundance clones and subclones, might also be of interest since they may have high affinity for the Ag. We show that the fraction of plasma cells (PCs) with high B-cell receptor (BcR) mRNA content in the GC does not significantly affect the number of dominant clones derived from single GCs by sequencing BcR mRNAs. Results from these simulations guide data interpretation and the design of follow-up experiments.

PMID:36927990 | DOI:10.1038/s41540-023-00271-y

Nature. 2023 Mar 16. doi: 10.1038/s41586-023-05932-w. Online ahead of print.

NO ABSTRACT

PMID:36927805 | DOI:10.1038/s41586-023-05932-w

Nat Rev Cardiol. 2023 Mar 16. doi: 10.1038/s41569-023-00847-5. Online ahead of print.

ABSTRACT

The prevalence of obesity has reached pandemic proportions, and now approximately 25% of adults in Westernized countries have obesity. Recognized as a major health concern, obesity is associated with multiple comorbidities, particularly cardiometabolic disorders. In this Review, we present obesity as an evolutionarily novel condition, summarize the epidemiological evidence on its detrimental cardiometabolic consequences and discuss the major mechanisms involved in the association between obesity and the risk of cardiometabolic diseases. We also examine the role of potential moderators of this association, with evidence for and against the so-called 'metabolically healthy obesity phenotype', the 'fatness but fitness' paradox or the 'obesity paradox'. Although maintenance of optimal cardiometabolic status should be a primary goal in individuals with obesity, losing body weight and, particularly, excess visceral adiposity seems to be necessary to minimize the risk of cardiometabolic diseases.

PMID:36927772 | DOI:10.1038/s41569-023-00847-5

Elife. 2023 Mar 16;12:e80671. doi: 10.7554/eLife.80671.

ABSTRACT

The hippocampus has been proposed to encode environments using a representation that contains predictive information about likely future states, called the successor representation. However, it is not clear how such a representation could be learned in the hippocampal circuit. Here, we propose a plasticity rule that can learn this predictive map of the environment using a spiking neural network. We connect this biologically plausible plasticity rule to reinforcement learning, mathematically and numerically showing that it implements the TD-lambda algorithm. By spanning these different levels, we show how our framework naturally encompasses behavioral activity and replays, smoothly moving from rate to temporal coding, and allows learning over behavioral timescales with a plasticity rule acting on a timescale of milliseconds. We discuss how biological parameters such as dwelling times at states, neuronal firing rates and neuromodulation relate to the delay discounting parameter of the TD algorithm, and how they influence the learned representation. We also find that, in agreement with psychological studies and contrary to reinforcement learning theory, the discount factor decreases hyperbolically with time. Finally, our framework suggests a role for replays, in both aiding learning in novel environments and finding shortcut trajectories that were not experienced during behavior, in agreement with experimental data.

PMID:36927625 | DOI:10.7554/eLife.80671

J R Coll Physicians Edinb. 2023 Mar 16:14782715231162675. doi: 10.1177/14782715231162675. Online ahead of print.

ABSTRACT

The fruit fly, Drosophila melanogaster, is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and in foundational insights into the molecular basis of development. From the 1930s until today, researchers at the University of Edinburgh have used Drosophila to tackle questions in basic and biomedical science. Here the history of the initial decades of this research is explored, beginning with the introduction of Drosophila research to Edinburgh by Francis Albert Eley Crew, in the newly established Institute of Animal Genetics. This period of research includes the discovery that chemicals can cause genetic mutation. This was demonstrated by research of the effects of mustard gas on flies by Charlotte Auerbach and colleagues, guided by the future Nobel laureate Hermann Muller. Drosophila research was also formative in Conrad Hal Waddington's conceptual thinking about developmental biology, including in his vision of the epigenetic landscape. This holistic, systems-level view of the control of development was far before its time and has continued to be influential to this day in our conceptualisation of developmental biology and in the increasingly important field of systems biology. Waddington's experiments with Drosophila in Edinburgh also gave rise to the evolutionary concept of genetic assimilation, in which an environmentally induced phenotype subsequently becomes genetically encoded.

PMID:36927337 | DOI:10.1177/14782715231162675

Microbiol Resour Announc. 2023 Mar 16:e0126422. doi: 10.1128/mra.01264-22. Online ahead of print.

ABSTRACT

Algoriphagus sp. strain PAP.12 (EXT111900) and Roseivirga sp. strain PAP.19 (EXT111901) were isolated from marine samples. Here, we report their draft genome sequences, 5.032 Mbp and 4.583 Mbp in size, respectively, and rate their specialized metabolite production capacity. Taxonomic ranks established by genome-based analysis indicate that Algoriphagus sp. strain PAP.12 represents a candidate new species.

PMID:36927116 | DOI:10.1128/mra.01264-22

Science. 2023 Mar 17;379(6637):eabg2482. doi: 10.1126/science.abg2482. Epub 2023 Mar 17.

ABSTRACT

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.

PMID:36927018 | DOI:10.1126/science.abg2482

iScience. 2023 Feb 18;26(3):106238. doi: 10.1016/j.isci.2023.106238. eCollection 2023 Mar 17.

ABSTRACT

RNA splicing dysfunctions are more widespread than what is believed by only estimating the effects resulting by splicing factor mutations (SFMT) in myeloid neoplasia (MN). The genetic complexity of MN is amenable to machine learning (ML) strategies. We applied an integrative ML approach to identify co-varying features by combining genomic lesions (mutations, deletions, and copy number), exon-inclusion ratio as measure of RNA splicing (percent spliced in, PSI), and gene expression (GE) of 1,258 MN and 63 normal controls. We identified 15 clusters based on mutations, GE, and PSI. Different PSI levels were present at various extents regardless of SFMT suggesting that changes in RNA splicing were not strictly related to SFMT. Combination of PSI and GE further distinguished the features and identified PSI similarities and differences, common pathways, and expression signatures across clusters. Thus, multimodal features can resolve the complex architecture of MN and help identifying convergent molecular and transcriptomic pathways amenable to therapies.

PMID:36926651 | PMC:PMC10011742 | DOI:10.1016/j.isci.2023.106238

Front Genet. 2023 Feb 27;14:1143382. doi: 10.3389/fgene.2023.1143382. eCollection 2023.

ABSTRACT

Gene regulatory networks are graph models representing cellular transcription events. Networks are far from complete due to time and resource consumption for experimental validation and curation of the interactions. Previous assessments have shown the modest performance of the available network inference methods based on gene expression data. Here, we study several caveats on the inference of regulatory networks and methods assessment through the quality of the input data and gold standard, and the assessment approach with a focus on the global structure of the network. We used synthetic and biological data for the predictions and experimentally-validated biological networks as the gold standard (ground truth). Standard performance metrics and graph structural properties suggest that methods inferring co-expression networks should no longer be assessed equally with those inferring regulatory interactions. While methods inferring regulatory interactions perform better in global regulatory network inference than co-expression-based methods, the latter is better suited to infer function-specific regulons and co-regulation networks. When merging expression data, the size increase should outweigh the noise inclusion and graph structure should be considered when integrating the inferences. We conclude with guidelines to take advantage of inference methods and their assessment based on the applications and available expression datasets.

PMID:36926589 | PMC:PMC10012345 | DOI:10.3389/fgene.2023.1143382

Front Artif Intell. 2023 Feb 28;6:1116870. doi: 10.3389/frai.2023.1116870. eCollection 2023.

ABSTRACT

The brain is arguably the most powerful computation system known. It is extremely efficient in processing large amounts of information and can discern signals from noise, adapt, and filter faulty information all while running on only 20 watts of power. The human brain's processing efficiency, progressive learning, and plasticity are unmatched by any computer system. Recent advances in stem cell technology have elevated the field of cell culture to higher levels of complexity, such as the development of three-dimensional (3D) brain organoids that recapitulate human brain functionality better than traditional monolayer cell systems. Organoid Intelligence (OI) aims to harness the innate biological capabilities of brain organoids for biocomputing and synthetic intelligence by interfacing them with computer technology. With the latest strides in stem cell technology, bioengineering, and machine learning, we can explore the ability of brain organoids to compute, and store given information (input), execute a task (output), and study how this affects the structural and functional connections in the organoids themselves. Furthermore, understanding how learning generates and changes patterns of connectivity in organoids can shed light on the early stages of cognition in the human brain. Investigating and understanding these concepts is an enormous, multidisciplinary endeavor that necessitates the engagement of both the scientific community and the public. Thus, on Feb 22-24 of 2022, the Johns Hopkins University held the first Organoid Intelligence Workshop to form an OI Community and to lay out the groundwork for the establishment of OI as a new scientific discipline. The potential of OI to revolutionize computing, neurological research, and drug development was discussed, along with a vision and roadmap for its development over the coming decade.

PMID:36925616 | PMC:PMC10013972 | DOI:10.3389/frai.2023.1116870

Anal Chim Acta. 2023 Apr 22;1251:340998. doi: 10.1016/j.aca.2023.340998. Epub 2023 Feb 22.

ABSTRACT

Non-specific amplification is a major problem in nucleic acid amplification resulting in false-positive results, especially for exponential amplification reactions (EXPAR). Although efforts were made to suppress the influence of non-specific amplification, such as chemical blocking of the template's 3'-ends and sequence-independent weakening of template-template interactions, it is still a common problem in many conventional EXPAR reactions. In this study, we propose a novel strategy to eliminate the non-specific signal from non-specific amplification by integrating the CRISPR-Cas12a system into two-templates EXPAR. An EXPAR-Cas12a strategy named EXPCas was developed, where the Cas12a system acted as a filter to filter out non-specific amplificons in EXPAR, suppressing and eliminating the influence of non-specific amplification. As a result, the signal-to-background ratio was improved from 1.3 to 15.4 using this method. With microRNA-21 (miRNA-21) as a target, the detection can be finished in 40 min with a LOD of 103 fM and no non-specific amplification was observed.

PMID:36925288 | DOI:10.1016/j.aca.2023.340998

Biochim Biophys Acta Mol Basis Dis. 2023 Mar 14:166688. doi: 10.1016/j.bbadis.2023.166688. Online ahead of print.

ABSTRACT

Cell-free heme (CFH) is a product of hemoglobin, myoglobin and hemoprotein degradation, which is a hallmark of pathologies associated with extensive hemolysis and tissue damage. CHF and iron collectively induce cytokine storm, lung injury, respiratory distress and infection susceptibility in the lungs suggesting their key role in the progression of lung disease pathology. We have previously demonstrated that heme-mediated reactive oxygen species (ROS) induces platelet activation and ferroptosis. However, interaction of ferroptotic platelets and neutrophils, the mechanism of action and associated complications remain unclear. In this study, we demonstrate that heme-induced P-selectin expression and Phosphatidylserine (PS) externalization in platelets via ASK-1-inflammasome axis increases platelet-neutrophil aggregates in circulation, resulting in Neutrophil extracellular traps (NET) formation in vitro and in vivo. Further, heme-induced platelet activation in mice increased platelet-neutrophil aggregates and accumulation of NETs in the lungs causing pulmonary damage. Thus, connecting CFH-mediated platelet activation to NETosis and pulmonary thrombosis. As lung infections induce acute respiratory stress, thrombosis and NETosis, we propose that heme -mediated platelet activation and ferroptosis might be crucial in such clinical manifestations. Further, considering the ability of redox modulators and ferroptosis inhibitors like FS-1, Lpx-1 and DFO to inhibit heme-induced ferroptotic platelets-mediated NETosis and pulmonary thrombosis. They could be potential adjuvant therapy to regulate respiratory distress-associated clinical complications.

PMID:36925054 | DOI:10.1016/j.bbadis.2023.166688

Microb Pathog. 2023 Mar 14:106066. doi: 10.1016/j.micpath.2023.106066. Online ahead of print.

ABSTRACT

BACKGROUND: s: Shigella spp. causes bloody diarrhea and leads to death, especially in children. Chimeric proteins containing virulence factors can prevent Shigella infection. The purpose of this study is to investigate the immunogenic and protective effect of trivalent chimeric protein containing IpaD-StxB-TolC antigens against shiga toxin, S. dysenteri and S. flexneri in vitro and in vivo conditions.

METHODS: Recombinant vector was transferred to E. coli BL21. The expression of the chimeric protein was confirmed by SDS PAGE and purified using the Ni-NTA column. Mice were immunized with recombinant protein and antibody titer was evaluated by ELISA. 10, 25 and 50 LD50 of Shiga toxin neutralization was evaluated in vitro (Vero cell line) and in vivo conditions. Also, the challenge of immunized mice with 10, 25 and 50 LD50 of S. dysentery and S. flexneri was done.

RESULTS: The expression and purification of the recombinant protein with 60.6 kDa was done. ELISA showed increased antibody titer against the chimeric protein. MTT assay indicated that 1/8000 dilution of the sera had a 51% of cell viability against the toxin in Vero cell line. The challenge of mice immunized with toxin showed that the mice had complete protection against 10 and 25 LD50 of toxin and had 40% survival against 50 LD50. Mice receiving 10 and 25 LD50 of S. dysenteri and S. flexneri had 100% protection and in 50 LD50 the survival rate was 60 and 50%, respectively. Organ burden showed that the amount of bacterial colonization in immunized mice was 1 × 104 CFU/mL, which was significantly different from the control group.

CONCLUSION: This study showed that chimeric proteins can create favorable immunogenicity in the host as vaccine candidates.

PMID:36924900 | DOI:10.1016/j.micpath.2023.106066

J Pharm Biomed Anal. 2023 Mar 6;228:115326. doi: 10.1016/j.jpba.2023.115326. Online ahead of print.

ABSTRACT

R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under - 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted to R14 bisulfite adduct, which was more stable in plasma and blood. The adduct has MRM transition at m/z 340.1-127.0 in negative mode and showed high sensitivity in LC-MS/MS quantification. Thus, monitoring the adduct provided a suitable way of quantitating R14 concentrations in mouse whole blood. The reacting conditions were optimized based on detecting R14 bisulfite adduct, and the assay was established and validated on a SCIEX 6500+ Triple Quad LC-MS/MS System. The method was then successfully adapted to pharmacokinetic studies after oral administration of R14 to mice.

PMID:36924633 | DOI:10.1016/j.jpba.2023.115326

Mass Spectrom Rev. 2023 Mar 16. doi: 10.1002/mas.21837. Online ahead of print.

ABSTRACT

Chemical proteomics, which involves studying the covalent modifications of proteins by small molecules, has significantly contributed to our understanding of protein function and has become an essential tool in drug discovery. Mass spectrometry (MS) is the primary method for identifying and quantifying protein-small molecule adducts. In this review, we discuss various methods for measuring proteomic reactivity using MS and covalent proteomics probes that engage through reactivity-driven and proximity-driven mechanisms. We highlight the applications of these methods and probes in live-cell measurements, drug target identification and validation, and characterizing protein-small molecule interactions. We conclude the review with current developments and future opportunities in the field, providing our perspectives on analytical considerations for MS-based analysis of the proteomic reactivity landscape.

PMID:36924435 | DOI:10.1002/mas.21837

Front Genet. 2023 Feb 27;14:1041103. doi: 10.3389/fgene.2023.1041103. eCollection 2023.

ABSTRACT

Grasscutter (Thryonomys swinderianus) is a large-body old world rodent found in sub-Saharan Africa. The body size and the unique taste of the meat of this major crop pest have made it a target of intense hunting and a potential consideration as a micro-livestock. However, there is insufficient knowledge on the genetic diversity of its populations across African Guinean forests. Herein, we investigated the genetic diversity, population structures and evolutionary history of seven Nigerian wild grasscutter populations together with individuals from Cameroon, Republic of Benin, and Ghana, using five mitochondrial fragments, including D-loop and cytochrome b (CYTB). D-loop haplotype diversity ranged from 0.571 (± 0.149) in Republic of Benin to 0.921 (± 0.013) in Ghana. Within Nigeria, the haplotype diversity ranged from 0.659 (± 0.059) in Cross River to 0.837 (± 0.075) in Ondo subpopulation. The fixation index (FST), haplotype frequency distribution and analysis of molecular variance revealed varying levels of population structures across populations. No significant signature of population contraction was detected in the grasscutter populations. Evolutionary analyses of CYTB suggests that South African population might have diverged from other populations about 6.1 (2.6-10.18, 95% CI) MYA. Taken together, this study reveals the population status and evolutionary history of grasscutter populations in the region.

PMID:36923796 | PMC:PMC10010571 | DOI:10.3389/fgene.2023.1041103

Front Chem. 2023 Feb 27;11:1124229. doi: 10.3389/fchem.2023.1124229. eCollection 2023.

ABSTRACT

Composition analysis in wine is gaining increasing attention because it can provide information about the wine quality, source, and nutrition. In this work, in situ liquid secondary ion mass spectrometry (SIMS) was applied to 14 representative wines, including six wines manufactured by a manufacturer in Washington State, United States, four Cabernet Sauvignon wines, and four Chardonnay wines from other different manufacturers and locations. In situ liquid SIMS has the unique advantage of simultaneously examining both organic and inorganic compositions from liquid samples. Principal component analysis (PCA) of SIMS spectra showed that red and white wines can be clearly differentiated according to their aromatic and oxygen-contained organic species. Furthermore, the identities of different wines, especially the same variety of wines, can be enforced with a combination of both organic and inorganic species. Meanwhile, in situ liquid SIMS is sample-friendly, so liquid samples can be directly analyzed without any prior sample dilution or separation. Taken together, we demonstrate the great potential of in situ liquid SIMS in applications related to the molecular investigation of various liquid samples in food science.

PMID:36923690 | PMC:PMC10008862 | DOI:10.3389/fchem.2023.1124229

Front Mol Biosci. 2023 Feb 27;10:1065171. doi: 10.3389/fmolb.2023.1065171. eCollection 2023.

ABSTRACT

Objective: To investigate and predict the targets and signaling pathways of sinomenium acutum (SA) in the treatment of rheumatoid arthritis (RA) through systems biology and network pharmacology, and to elucidate its possible mechanisms of action. Methods: We screened the active ingredients and corresponding target proteins of SA in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN); and obtained the targets of rheumatoid arthritis diseases in a database of gene-disease associations (DisGeNET), Online Mendelian Inheritance in Man (OMIM) database. The two targets were mapped by Venn diagram and the intersection was taken. The intersecting targets were used to construct protein-protein interaction (PPI) network maps in the String database, and Metascape was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, the molecular docking technique was applied to validate and further clarify the core target of SA for the treatment of rheumatoid arthritis. Results: A total of six active ingredients and 217 potential targets were obtained after screening; 2,752 rheumatoid arthritis-related targets and 66 targets common to RA and SA. GO function and KEGG pathway enrichment analysis yielded 751 GO function entries (652 GO biological processes, 59 GO molecular functions and 40 GO cellular components) and 77 KEGG signaling pathways. It mainly involves pathways related to neural activity ligand-receptor interaction pathways, cancer pathways, calcium signaling channels, Th17 cell differentiation and others, which are mainly classified into four categories, including regulation of immunity, anti-inflammation, regulation of cell growth and apoptosis, and signaling. The molecular docking results showed that the binding energy of PTGS2, CASP3, JUN and PPARG to the key components beta-sitosterol, 16-epi-Isositsirikine, Sinomenine and Stepholidine were ≤ -6.5 kcal/mol, suggesting the existence of molecular binding sites. Conclusion: SA acts on key targets such as PTGS2, CASP3, JUN, and PPARG to modulate signaling pathways such as neural activity ligand-receptor interaction, cancer, calcium ion, NF-κB, and Th17 cell differentiation to regulate immunity, anti-inflammation, modulation of cell cycle, bone metabolism, and signaling for the treatment of RA. It was also confirmed that the treatment of RA with SA has multi-component, multi-target, multi-pathway and multi-mechanism characteristics.

PMID:36923645 | PMC:PMC10009275 | DOI:10.3389/fmolb.2023.1065171