GO Enrichment Research Articles

Identification of Associations with Dermatologic Diseases through a Focused GWAS of the UK Biobank

The UK Biobank includes genotype information for about 500,000 patients for over 7,000 phenotypes. However, due to multiple testing correction for approximately 200 billion tests, many clinically and statistically significant associations remain unappreciated. We perform a focused analysis of the UK Biobank for 13 dermatologic conditions, including malignant melanoma, melanoma in situ, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, seborrheic keratosis, psoriasis, lichen planus, systemic lupus erythematosus, hyperhidrosis, pilonidal cyst, sebaceous cyst, and lipoma. We identify 447 sentinel variants, which are enriched for protein-coding variants and an elevated CADD score compared to background variants. Through GO enrichment analysis, we identify known pathways involved in melanoma, actinic keratoses, and squamous cell carcinoma and uncover pathways. We also uncover 5 protein-coding variants, which to our knowledge have not been previously reported, including LRP3 for lipomas, PLCD1 for sebaceous cysts, EIF3CL for lichen planus, TTK for pilonidal cysts, and MAPK15 for systemic lupus erythematosus.

Differentiation of long Non-Coding RNA expression profiles in three Fruiting stages of grape

Grapes are considered a crucial fruit crop with extensive uses globally. Cluster compactness is an undesirable trait for the productivity of Yaghooti grape, and it reduces its desirability among consumers. The RNA-Seq data were analyzed in three stages of cluster development using the FEELnc software, leading to the identification of 849 lncRNAs. 183 lncRNAs were differentially expressed during cluster development stages. The GO and KEGG enrichment analyses of these lncRNAs revealed that they target 1,814 genes, including CKX, PG, PME, NPC2, and UGT. The analysis demonstrated a relationship between these lncRNAs and key processes such as grape growth and development, secondary metabolite synthesis, and resistance to both biotic and abiotic stresses. These findings, combined with molecular experiments on lncRNA interactions with other regulatory factors, could enhance Yaghooti grape quality and decrease cluster compactness.

UPLC-Q-TOF-MS/MS Combined with Network Pharmacology, Molecular Docking, and Animal Verification Reveals the Mechanism of Insomnia Treatment by Shen Qi Wu Wei Zi Capsules.

Shen Qi Wu Wei Zi capsules (SQWWZ) are often used to treat insomnia; however, the potential therapeutic mechanism is still unclear. This study aimed to investigate the mechanism underlying the therapeutic effects of the Shen Qi Wu Wei Zi capsules on insomnia. The components of SQWWZ were identified using the UPLC-Q-TOF-MS/MS technique in conjunction with relevant literature. Insomnia-related targets were searched in the Gene- Cards and DisGeNET databases, and the intersection targets were obtained using a Venn diagram. A component-target-insomnia network diagram was constructed using Cytoscape 3.7.2 software. Core targets underwent GO and KEGG enrichment analyses. Molecular docking techniques were employed to verify the key proteins involved in the pathway and their corresponding compounds. Insomnia was induced in SD rats through the intraperitoneal injection of pchlorophenylalanine (DL-4-chlorophenylalanine, PCPA). The rats were treated orally with SQWWZ, and the serum levels of 5-HT and GABA in each group were determined using ELISA. Histological analysis of hippocampal tissue sections from the rats was performed using HE staining. Using UPLC-Q-TOF-MS/MS and reviewing relevant literature, we identified 49 components of SQWWZ. Additionally, we obtained 1,043 drug targets and 367 insomnia-related targets. Among these, 82 targets were found to be common to both drug and insomnia targets. Following drug administration, rats in the treatment group exhibited a significant increase in the serum levels of 5-HT and GABA. Moreover, histological analysis using HE staining revealed neatly arranged hippocampal neuronal cells in the treated rats. The active components of SQWWZ had good inhibition of insomnia. This study provides a reference and guidance for the in-depth study of SQWWZ for the treatment of insomnia.

Comprehensive analysis of the m6A demethylase FTO in endothelial dysfunction by MeRIP sequencing

N6-methyladenosine (m6A) is the most general post-transcriptional modification of eukaryotic mRNAs and long-stranded non-coding RNAs. In this process, It has been shown that FTO associates with the m6A mRNA demethylase and plays a role in diabetic vascular endothelial dysfunction. In the present study, we detected FTO protein expression in HUVECs by Western blot and found that FTO was highly expressed in all disease groups relative to the control group. To explore the mechanism of FTO in T2DM vasculopathy, we performed an analysis by methylated RNA immunoprecipitation sequencing (MeRIP-seq) to elucidate the role of aberrant m6A modification and mRNA expression in endothelial dysfunction. The results showed 202 overlapping genes with varying m6A modifications and varied mRNA expression, and GO and KEGG enrichment analysis revealed that these genes were predominantly enriched in pathways associated with T2DM complications and endothelial dysfunction. By an integrated analysis of MeRIP-seq and RNA-seq results, the IGV plots showed elevated kurtosis of downstream candidate gene modifications, which may be downstream targets for FTO to exercise biological functions. HOXA9 and PLAU mRNA expression levels were significantly down after FTO inhibition. In the current work, we set up a typological profile of the m6A genes among HUVECs as well as uncovered a hidden relationship between RNA methylation modifications for T2DM vasculopathy-associated genes. Taken together, this study indicates that endothelial functional impairment is present in T2DM patients and may be related to aberrant expression of FTO.

Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone.

The aim of this study was to explore the role of NADH:ubiquinone oxidoreductase subunit B3 (NDUFB3) in human gynecological malignancies and to screen potential natural compounds targeting it. GEPIA and HPA databases were used to study the expression characteristics of NDUFB3. GO and KEGG enrichment analyses were performed using the R software clusterProfiler package. GSEA for NDUFB3 was performed using the LinkedOmics database. Natural compounds targeting NDUFB3 were screened by virtual screening and molecular docking. After NDUFB3 was depleted or wedelolactone treatment, cell proliferation was detected by CCK-8 assay. The production of reactive oxide species (ROS) in tumor cells was detected by dihydroethidium fluorescent probe. The cell cycle and apoptosis were evaluated by flow cytometry. It was revealed that NDUFB3 was highly expressed in ovarian cancer (OV), uterine corpus endometrial carcinoma (UCEC), and cervical squamous cell carcinoma (CESC). NDUFB3 expression was associated with multiple immunomodulators in CESC, OV, and UCEC. NDUFB3 was predicted to modulate MAPK signaling pathways in CESC, OV, and UCEC. Knocking down NDUFB3 inhibited the proliferation of CESC, OV, and UCEC cells, increased intracellular ROS production, and induced cell cycle arrest and apoptosis. Wedelolactone was a potential small molecule with a strong ability to bind with the active pocket of NDUFB3, and wedelolactone could kill CESC, OV, and UCEC cells partly via NDUFB3. In conclusion, NDUFB3 may be a potential biomarker and a new target for gynecological tumors, and wedelolactone may exert antitumor activity via targeting NDUFB3.

Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches

Hormone replacement therapy is used to treat postmenopausal syndrome caused by estrogen deficiency, but it has been linked to an increased risk of breast cancer. In India, Achyranthes aspera L. is traditionally used to treat menstrual problems; however, there is a lack of mechanistic evidence of its phytoestrogenicity. Therefore, this study investigated the estrogenic activity of A. aspera on estrogen-responsive MCF-7 breast cancer cells. In a cell proliferation assay, the MeOH fraction (100 μg/mL) exhibited the highest proliferation effect (PE) of 138 % (p < 0.001) and relative proliferation effect (RPE) of 96.5 %, compared to 17β-estradiol (0.01 μM: 143 % PE, p < 0.001; 100 % RPE). The MeOH fraction was shown to upregulate the oestrogen marker genes trefoil factor 1 and progesterone receptor by 20.14–23.94 folds and 10.83–14.83 folds, respectively. Twelve phenolics were identified by LC-MS/MS in the active MeOH fraction, i.e. quinic acid, kaempferol hexoside, kaempferol 3-O-(2″-O-galloyl)-glucoside)-β-D-glucoside, geniposide, 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol, kaempferol-3-O-glucoside (astragalin), 3,30-di-O-methylellagic acid isomer, procyanidin, naringin, propapyriogenin A2, (3β,22E,24R)-23-methylergosta-5,7,22-trien-3-ol and 6-prenylapigenin. Through network pharmacology, the potential effects, and mechanisms of these compounds in osteoporosis were revealed. About 55 target genes were linked to osteoporosis. GO and KEGG enrichment suggest regulation of female reproductive hormone related signaling pathways, which are also associated with estrogen dependent osteoporosis. Molecular docking analysis of the compounds revealed potential interactions with hERα receptor for 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol and kaempferol-3-O-glucoside (astragalin) (docking scores of −9.3 and −10.1 kcal/mol, respectively) as compared to 17β-estradiol (−9.3 kcal/mol). These results suggest the estrogenicity of A. aspera via an ERα-associated mechanism and support its traditional usage in the management of menopausal-related problems.

Predictive value of miR-636 in patients with acute myocardial infarction undergoing percutaneous coronary intervention and its bioinformatics analysis

BackgroundMicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI). Percutaneous coronary intervention (PCI) is currently the most direct and effective procedure to treat AMI, but the occurrence of postoperative cardiovascular events (MACE) affects patients’ quality of life. The objective of this study was to identify a new biomarker that could provide a theoretical basis for the prevention of MACE in patients with AMI undergoing PCI.Methods142 AMI patients who underwent PCI and 130 healthy volunteers were selected as study subjects. Detection of miR-636 expression level by fluorescence quantitative PCR. ROC, Kaplan-Meier and Cox regression analyses were applied to evaluate the diagnostic and prognostic value of miR-636 for AMI. The miR-636 target genes were predicted and enriched for GO function and KEGG pathway.ResultsMiR-636 expression levels were elevated in patients with AMI. ROC curve analysis showed that miR-636 had a feasible diagnostic value in distinguishing AMI patients from healthy controls miR-636 expression levels were elevated in patients who developed MACEs. ROC results showed that miR-636 had significant diagnostic value in differentiating AMI patients with and without MACEs after PCI treatment. GO and KEGG enrichment analyses showed that miR-636 may transmit information to vesicles formed by the cell membrane.ConclusionsMiR-636 expression serves as a biomarker for diagnosing AMI and predicting the occurrence of MACE after PCI.

A multi-omics database for the biological study of Osmanthus fragrans

Osmanthus fragrans Lour. is a well-known aromatic plant widely used as a food ingredient due to its unique floral fragrance and bioactive compounds. To fully utilize O. fragrans resources, we established an O. fragrans multi-omics database called the O. fragrans Information Resource (OfIR: http://yanglab.hzau.edu.cn/OfIR/home/). OfIR is a convenient and comprehensive multi-omics database that efficiently integrates phenotype and genetic variation from 127 O. fragrans cultivars, and provides many easy-to-use analysis tools, including primer design, sequence extraction, multi-sequence alignment, GO and KEGG enrichment analysis, variation annotation, and electronic PCR. Two case studies were used to demonstrate its power to mine candidate genetic variation sites or genes associated with specific traits or regulatory networks. In summary, the multi-omics database OfIR provides a convenient and user-friendly platform for researchers in mining functional genes and contributes to the genetic breeding of O. fragrans.

Exploring the molecular targets of fingolimod and siponimod for treating the impaired cognition of schizophrenia using network pharmacology and molecular docking

The treatment of cognitive impairment in schizophrenia is an unaddressed need due to the absence of novel treatments. Recent studies demonstrated that fingolimod and siponimod have neuroprotective effects in several neuropsychiatric disorders; however, their pharmacological mechanisms are unclear. The objective of this study was to identify potential molecular mechanisms of fingolimod and siponimod for improving cognition of schizophrenia through network pharmacology and molecular docking. The putative target genes of ingredients, schizophrenia, and impaired cognition were obtained from online databases, including SwissTargetPrediction, PharmMapper, GeneCards, CTD, DisGeNET, and OMIM. A protein–protein interaction network was constructed to identify core targets. The DAVID database was used for GO and KEGG pathway enrichment analyses. An ingredient–target–pathway–disease network was constructed using Cytoscape. Finally, the interactions between ingredients and core targets were assessed with molecular docking. The analysis revealed 260 targets shared by fingolimod and siponimod, 257 unique targets for fingolimod, and 88 unique targets for siponimod. Two signaling pathways were involved in fingolimod-mediated improvements in the cognition of schizophrenia, including the PI3K-Akt and MAPK signaling pathways. The core targets that regulated these two pathways included IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF. The MAPK signaling pathway was involved in siponimod-mediated improvement in the cognition of schizophrenia. The MAPK pathway was regulated by three core targets, namely TNF, AKT1, and CASP3. Docking scores ranged from −5.0 to −10.4 kcal/mol. Our analysis revealed that fingolimod regulates the PI3K-Akt and MAPK signaling pathways via the core targets IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF, and siponimod regulates the MAPK signaling pathways via the core targets AKT1, TNF, and CASP3 to improve the cognition of schizophrenia. Our results provide potential targets and a theoretical basis for the design of new drugs to treat the impaired cognition of schizophrenia.

Polyenylphosphatidylcholine alleviates cardiorenal fibrosis, injury and dysfunction in spontaneously hypertensive rats by regulating Plpp3 signaling.

Polyenylphosphatidylcholine (PPC), a significant therapeutic agent for liver repair, exhibits potent antioxidant and anti-inflammatory properties. Nonetheless, its impact on hypertension and hypertensive vascular diseases requires clarification. Our objective was to elucidate the protective role and mechanism of PPC in a spontaneously hypertensive rat model. Male WKY and SHRs were randomly assigned to four groups: WKY control, SHRs control, SHRs treated with Telmisartan (SHR-TS), and SHRs treated with PPC (SHR-PPC). Blood pressure was monitored biweekly during the treatment. Histological analyses assessed aortic vascular remodeling and cardiac and renal injuries. RNA-seq was performed on vascular smooth muscle cells (VSMCs) isolated from WKY or SHRs, and protein levels of target genes were quantified using Western blotting. In a dose-dependent screening test, we confirmed that PPC (200 mg/kg/day) effectively reduced blood pressure in SHRs. Treatment with PPC also mitigated cardiac and renal injury in SHRs by attenuating hypertrophy and fibrosis. Compared to WKY rats, SHRs exhibited increased intima thickness, reduced vascular tone, and heightened aortic fibrosis; however, PPC treatment significantly reversed vascular remodeling. Analysis of RNA-seq data revealed that downregulated genes were enriched in inflammation and oxidative stress pathways based on GO and KEGG enrichment analyses. PPC markedly inhibited genes such as Rela, Relb, Nfkb2, and others involved in the NF-κB pathway. Given PPC's influence on glycerophospholipid synthesis and metabolism, and its role in NF-κB-mediated transcription affecting oxidative stress and inflammation, changes in the PLAs, PLPs, and PLPPs families were analyzed in PPC-treated VSMCs. Among these, PPC notably inhibited Plpp3. Importantly, overexpression of Plpp3 significantly reversed the protective effects of PPC on hypertension-related cardiac and renal injuries, vascular fibrosis, remodeling, and tension. We identified a new protective role for PPC in mitigating cardiac and renal injuries associated with hypertension, as well as in preventing aortic fibrosis and remodeling. Targeting the NF-κB/Plpp3 pathway may offer a promising therapeutic strategy for treating vascular diseases related to hypertension.

Identification, Cloning, and Characterization of Two Acupuncture-Injury-Inducing Promoters in Rice

As an important global food crop, rice is damaged by a variety of piercing–sucking pests. Identifying a broad-spectrum promoter induced by the physical signal of sucking pests and applying it to transgenic breeding to mitigate the damage caused by different sucking pests will significantly improve the efficiency of our breeding. This study compared the transcriptome changes in two rice varieties under needle-wounding stress to investigate their differential responses to mechanical damage. The results showed that the insect-susceptible variety TN1 exhibited more differentially expressed genes (DEGs) and greater changes in expression levels after needle treatment, indicating a more active internal gene regulatory network. GO and KEGG enrichment analysis further revealed that TN1 not only exhibited changes in genes related to the extracellular environment, but also mobilized more genes associated with stress response and defense. By screening the differentially expressed genes, we identified two promoters (P1 and P2) with inducible expression characteristics in both the resistant and susceptible rice varieties. These promoters were able to effectively drive the expression of the insect resistance gene OsLecRK1* and enhance the resistance of transgenic plants against the brown planthopper. This study provides promoter resources for the development of insect-resistant transgenic crops.

Identification of functional circRNAs regulating ovarian follicle development in goats

BarkgroundCircular RNAs (circRNAs) play important regulatory roles in a variety of biological processes in mammals. Multiple birth-traits in goats are affected by several factors, but the expression and function of circRNAs in follicular development of goats are not clear. In this study, we aimed to investigate the possible regulatory mechanisms of circRNA and collected five groups of large follicles (Follicle diameter > 6 mm) and small follicles (1 mm < Follicle diameter < 3 mm) from Leizhou goats in estrus for RNA sequencing.ResultsRNA sequencing showed that 152 circRNAs were differentially expressed in small and large follicles. Among them, 101 circRNAs were up-regulated in large follicles and 51 circRNAs were up-regulated in small follicles. GO and KEGG enrichment analyses showed that parental genes of the differential circRNAs were significantly enriched in important pathways, such as ovarian steroidogenesis, GnRH signaling pathway, animal autophagy and oxytocin signalling pathway. BioSignal analysis revealed that 152 differentially expressed circRNAs could target 91 differential miRNAs including miR-101 family (chi-miR-101-3p, chi-miR-101-5p), miR-202 family (chi-miR-202-5p, chi-miR-202-3p),60 circRNAs with translation potential. Based on the predicted sequencing results, the ceRNA networks chicirc_008762/chi-miR-338-3p/ARHGAP18 and chicirc_040444/chi-miR-338-3p/STAR were constructed in this study. Importantly, the new gene circCFAP20DC was first discovered in goats. The EDU assay and flow cytometry results indicated that circCFAP20DC enhanced the proliferation of follicular granulosa cells(GCs). Real-time quantitative PCR and western blotting assays showed that circCFAP20DC activated the Retinoblastoma(RB) pathway and promoted the progression of granulosa cells from G1 to S phase.ConclusionDifferential circRNAs in goat size follicles may have important biological functions for follicular development. The novel gene circCFAP20DC activates the RB pathway, promoting the progression of GCs from G1 to S phase. This, in turn, enhances the proliferation of follicular GCs in goats.

Integrating network pharmacology and experimental validation to decipher the pharmacological mechanism of DXXK in treating diabetic kidney injury

Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di’ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein–protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.

Transcriptome-based analysis of key functional genes in the triterpenoid saponin synthesis pathway of Platycodon grandiflorum

BackgroundPlatycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited.ResultsThis study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum.ConclusionsThe present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages.

Network Pharmacology and Molecular Docking to Explore the Mechanism of Action of Danxiong Huoxue Tablets for the Prevention and Treatment of Heterotopic Ossification

Background: Danxiong Huoxue tablets have been used clinically to prevent and treat Heterotopic Ossification (HO) after total hip arthroplasty, but its therapeutic mechanism is not clear. background: Danxiong Huoxue Tablets has been used clinically to prevent and treat heterotopic ossification (HO) after total hip arthroplasty, but its therapeutic mechanism is not clear. Objectives: This study investigated the potential mechanism of action of Danxiong Huoxue tablets against HO using network pharmacology and molecular docking methods. Methods: The TCMID and SymMap databases and the existing literature were used to screen the active ingredients and targets of Danxiong Huoxue tablets, and the targets of heterotopic ossification were obtained from Gene Cards, DisGeNET, and PharmGkb databases. The PPI network diagram was constructed using the String database and Cytoscape 3.9.1 software. Finally, the core targets were analyzed by GO and KEGG enrichment and validated by molecular docking. Results: A total of 39 active ingredients and 328 corresponding targets of Danxiong Huoxue tablets were identified, which were enriched in signaling pathways, such as PI3K/Akt and MAPK. Molecular docking verified that there was good binding activity between the core targets and the corresponding components. Conclusion: Danxiong Huoxue tablets may prevent and treat HO by acting on key targets, such as SRC, AKT1, JUN, and TNF, and regulating the PI3K/Akt signaling pathway and MAPK signaling pathway.

Mechanisms of Action of the Herba Salviae Chinensis-Fructus Akebiae Pair in the Treatment of Non-small Cell Lung Cancer based on a Network Pharmacology Study

Objective: To study the active ingredients and mechanism of action of "Herba Salviae Chinensis-Fructus Akebiae" drug pair in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology to provide theoretical basis for clinical application. Methods: The TCMSP (Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform) was used to obtain the active ingredients and targets of "Herba Salviae Chinensis-Fructus Akebiae", and the results were analyzed by the Genecard (https://genecard, org/) database, the Online Mendelian Inheritance Network (OMI), the Genecard database, the Genecard database, and the Online Mendelian Inheritance Network. We searched the Genecard (https://genecard, org/) database and the Online Mendelian Inheritance in Man (OMIM) database (http://omim. org/) for non-small cell lung cancer (NSCLC) disease targets by selecting "NSCLC" as a keyword, and then obtained the results of the "Herba Salviae Chinensis-Fructus Akebiae" drug pair by using venn. We used venn to obtain the intersecting targets of the drug pair "Herba Salviae Chinensis-Fructus Akebiae" and NSCLC, and then used the STRING database and Cytoscape to construct a common target visualization network diagram. The gene (GO) enrichment analysis and KEGG enrichment analysis were realized with the help of metascape database and Microbiology platform. Results: Five active ingredients of Ishiminokan-Precipitant were obtained, and 3695 non-small cell lung cancer targets and 123 common targets were obtained. GO analysis showed that the process of GO enrichment was mainly related to the regulation of responses to inorganic substances, transcriptional regulatory complexes, cytokine receptor binding, etc. KEGG enrichment showed that the process of KEGG enrichment was mainly through Pathways in Cancer, ILRT, and cytokine receptor binding. KEGG enrichment showed that KEGG mainly exerted anti-cancer effects through pathways in cancer and IL-17 signaling pathway. Conclusion: Using the method of network pharmacology, it is proved that the drug pair "Herba Salviae Chinensis-Fructus Akebiae" can exert therapeutic effects on NSCLC through multi-components, multi-targets, and multi-pathways, and provides the theoretical basis for the clinical application.

ABA-regulated MAPK signaling pathway promotes hormesis in sugar beet under cadmium exposure

Sugar beet (Beta vulgaris L.) shows potential as an energy crop for cadmium (Cd) phytoremediation. To elucidate its in vivo response strategy to Cd exposure, seedlings were treated with 1, 3, and 5 mmol/L CdCl2 (Cd-1, Cd-3, and Cd-5) for 6 h, using 0 mmol/L CdCl2 (Cd-0) as the control. The results showed that Cd-3 promoted a unique “hormesis” effect, leading to superior growth performance, increased levels of chlorophyll, soluble protein, and SOD activity, and reduced MDA content in sugar beet, compared to Cd-1, Cd-5, and even Cd-0. GO and KEGG enrichments and PPI networks of transcriptomic analysis revealed that the differentially expressed genes (DEGs) were primarily involved in lipid metabolism, cellular protein catabolism, and photosynthesis. Notably, the MAPK signaling pathway was significantly enriched only under Cd-3, with the up-regulation of ABA-related core gene BvPYL9 and an increase in ABA content after 6 h of Cd exposure. Furthermore, overexpression of BvPYL9 in Arabidopsis thaliana (OE-1 and OE-2) resulted in enhanced growth (fresh weight, dry weight, and root length), as well as higher ABA and soluble protein contents under different Cd treatments. Cd-induced transcriptional responses of BvPYL9 were also evident in OE-1 and OE-2, especially at 10 µmol/L, indicated by qRT-PCR. These findings suggest that ABA-mediated MAPK signaling pathway is activated in response to Cd toxicity, with BvPYL9 being a key factor in the cascade effects for the Cd-induced hormesis in sugar beet.

Exploring the Potential Effects and Mechanism of Astragalus Membranaceus in Treating Ischemic Heart Failure Based on Network Pharmacology and Experimental Verification.

Astragalus membranaceus (AM) is a traditional Chinese medicine that has been clinically utilized as an adjunctive therapy for the treatment of myocardial ischemia and heart failure; however, its precise molecular mechanism of action remains unknown. This study aims to investigate the potential pharmacological effects and molecular mechanism of AM in the treatment of ischemic heart failure (IHF) using network pharmacology methods, molecular docking technology, and in vitro experiments. The active components and targets of AM were obtained from the TCMSP databases, while the disease targets of IHF were retrieved from GeneCards and OMIM databases. The analysis of overlapping targets between AM and IHF mainly included active compounds-targets network, PPI network, and GO and KEGG enrichment analysis. The association between active compounds and target proteins was verified through molecular docking. Additionally, an in vitro experimental model was used to evaluate the accuracy of the forecast results. The network pharmacological analysis revealed that quercetin, kaempferol, 7-Omethylisomucronulatol, formononetin, and isorhamnetin were the core active components of AM in treating IHF. The core targets included AKT1, IL6, IL1B, PTGS2, CASP3, MMP9, and HIF1A. The molecular docking results demonstrated a strong binding affinity between these active components and targets. The KEGG pathway analysis suggested that the PI3K-AKT signaling pathway might play a central role in mediating AM's therapeutic effects on IHF. In vitro experiments demonstrated that AM treatment enhanced cell viability, reduced heart failure biomarkers, and suppressed cell apoptosis. Furthermore, the western blot analyses indicated that AM treatment effectively regulated AKT1 phosphorylation in an experimental model of IHF. Through integrated network pharmacological analysis, molecular docking technology, and in vitro experimental validation, it was demonstrated that AM can effectively mitigate IHF through activating PI3K-AKT signaling pathway. These findings significantly advance our understanding of the molecular mechanisms in IHF treatment and contribute further to promoting the clinical application of AM.

Genome-Wide Association Studies of Hair Whorl in Pigs.

In pigs, a hair whorl refers to hairs that form a ring of growth around the direction of the hair follicle at the dorsal hip. In China, a hair whorl is considered a negative trait that affects marketing, and no studies have been conducted to demonstrate whether hair whorl affects pig performance and provide an explanation for its genetic basis. Performance-measured traits and slaughter-measured traits of hair whorl and non-hair whorl pigs were differentially analyzed, followed by genome-wide association analysis (GWAS) and copy number variation (CNV) methods to investigate the genetic basis of hair whorl in pigs. Differential analysis of 2625 pigs (171 hair whorl and 2454 non-hair whorl) for performance measures showed that hair whorl and non-hair whorl pigs differed significantly (p < 0.05) in traits such as live births, total litter size, and healthy litter size (p < 0.05), while differential analysis of carcass and meat quality traits showed a significant difference only in the 45 min pH (p = 0.0265). GWAS identified 4 SNP loci significantly associated with the hair whorl trait, 2 of which reached genome-significant levels, and 23 candidate genes were obtained by annotation with the Ensembl database. KEGG and GO enrichment analyses showed that these genes were mainly enriched in the ErbB signaling, endothelial apoptosis regulation, and cell proliferation pathways. In addition, CNV analysis identified 652 differential genes between hair whorl and non-hair whorl pigs, which were mainly involved in the signal transduction, transcription factor activity, and nuclear and cytoplasmic-related pathways. The candidate genes and copy number variation differences identified in this study provide a new theoretical basis for pig breeding efforts.

Discovery of a novel Wolbachia in Heterodera expands nematode host distribution.

Bioinformatics sequence data mining can reveal hidden microbial symbionts that might normally be filtered and removed as contaminants. Data mining can be helpful to detect Wolbachia, a widespread bacterial endosymbiont in insects and filarial nematodes whose distribution in plant-parasitic nematodes (PPNs) remains underexplored. To date, Wolbachia has only been reported a few PPNs, yet nematode-infecting Wolbachia may have been widespread in the evolutionary history of the phylum based on evidence of horizontal gene transfers, suggesting there may be undiscovered Wolbachia infections in PPNs. The goal of this study was to more broadly sample PPN Wolbachia strains in tylenchid nematodes to enable further comparative genomic analyses that may reveal Wolbachia's role and identify targets for biocontrol. Published whole-genome shotgun assemblies and their raw sequence data from 33 Meloidogyne spp. assemblies, seven Globodera spp. assemblies, and seven Heterodera spp. assemblies were analyzed to look for Wolbachia. No Wolbachia was found in Meloidogyne spp. and Globodera spp., but among seven genome assemblies for Heterodera spp., an H. schachtii assembly from the Netherlands was found to have a large Wolbachia-like sequence that, when re-assembled from reads, formed a complete, circular genome. Detailed analyses comparing read coverage, GC content, pseudogenes, and phylogenomic patterns clearly demonstrated that the H. schachtii Wolbachia represented a novel strain (hereafter, denoted wHet). Phylogenomic tree construction with PhyloBayes showed wHet was most closely related to another PPN Wolbachia, wTex, while 16S rRNA gene analysis showed it clustered with other Heterodera Wolbachia assembled from sequence databases. Pseudogenes in wHet suggested relatedness to the PPN clade, as did the lack of significantly enriched GO terms compared to PPN Wolbachia strains. It remains unclear whether the lack of Wolbachia in other published H. schachtii isolates represents the true absence of the endosymbiont from some hosts.