Lipid Metabolism Response Research Articles

Lipid metabolism, immune and apoptosis transcriptomic responses of the hepatopancreas of Chinese mitten crab to the exposure to microcystin-LR

Global warming is favouring the incidence, intensity and duration of harmful cyanobacterial blooms. Microcystin-LR (MC-LR), a hepatotoxic agent, is produced during cyanobacterial blooms. To understand the molecular mechanisms of acute hepatotoxic effect of low doses of MC-LR in crab, we examined differentially expressed genes in samples of the hepatopancreas of Chinese mitten crab (Eriocheir sinensis) collected in 48 h after injections of MC-LR at doses of 0, 25, 50, and 75 µg/kg. The results revealed that MC-LR induced changes in corresponding gene led to the accumulation of triglycerides. MC-LR exposure affected sterol metabolism. Apoptosis-related genes such as Fas-L, Bcl-XL, Cytc, AiF, p53, PERK, calpain, CASP2, CASP7, α-tubulin, PARP, GF, G12, and PKC were upregulated. Conversely, expression levels of CASP10 and ASK1 were downregulated. Genes related to the regulation of actin cytoskeleton (Rho, ROCK, MLCP, MLC, PAK, and PFN) were upregulated. Further, expression levels of genes encoding fatty acid elongation-related enzymes were upregulated, but the expression of genes related to fatty acid synthesis was slightly down regulated. Taken together, these results demonstrated the hepatic toxicity and molecular mechanisms of changes in lipid metabolism, immune and apoptosis in Chinese mitten crab under the MC-LR-induced stress, which is the first report on crabs and performs a comprehensive analysis and a new insight of the molecular toxicological responses in crabs.

Dietary Supplementation With Fine-Grinding Wheat Bran Improves Lipid Metabolism and Inflammatory Response via Modulating the Gut Microbiota Structure in Pregnant Sow.

This study investigated the effects of fine-grinding wheat bran on pregnant sow body condition, lipid metabolism, inflammatory response, and gut microbiota. In this study, wheat bran was crushed into three particle sizes. A total of 60 Landrace × Yorkshire second parity sows were allotted to two groups: CWB (a diet containing coarse wheat bran with particle size of 605 μm) and FWB (a diet containing fine wheat bran with particle size of 438 μm). Fine-grinding wheat bran had higher soluble dietary fiber concentration, swelling capacity, water-holding capacity, and fermentability than coarse wheat bran. Pregnant sows fed FWB throughout pregnancy had lower body weight and fat deposition than sows fed CWB. And the piglet body weight at birth of the FWB group was remarkably increased. Serum concentrations of lipids (triglycerides, total cholesterol, and free fatty acid), interleukin 6, leptin, and resistin were decreased on day 90 of pregnancy by fine wheat bran supplementation. Feeding FWB significantly decreased abundance of Firmicutes and dramatically increased the abundance of Bacteroidetes at phylum level. At genus level, the abundance of Terrisporobacter was decreased in FWB feeding sows, but the abundance of Parabacteroides was increased. Fecal total short-chain fatty acids, propionate, and butyrate contents were markedly increased in the FWB group. The results suggested that the physicochemical properties of finely ground wheat bran had been improved. Dietary supplementation with fine wheat bran changed the gut microbiota structure and enhanced the short-chain fatty acids level, which improved the maternal body condition, metabolic and inflammatory status, and reproductive performance in sows.

Clr-f expression regulates kidney immune and metabolic homeostasis

The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1−/−Clr-f−/− background reveals that Clr-f−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.

Molecular Genetics and Cytotoxic Responses to Titanium Diboride and Zinc Borate Nanoparticles on Cultured Human Primary Alveolar Epithelial Cells

Titanium diboride (TiB2) and zinc borate (Zn3BO6) have been utilized in wide spectrum industrial areas because of their favorable properties such as a high melting point, good wear resistance, high hardness and thermal conductivity. On the other hand, the biomedical potentials of TiB2 and Zn3BO6 are still unknown because there is no comprehensive analysis that uncovers their biocompatibility features. Thus, the toxicogenomic properties of TiB2 and Zn3BO6 nanoparticles (NPs) were investigated on human primary alveolar epithelial cell cultures (HPAEpiC) by using different cell viability assays and microarray analyses. Protein-Protein Interaction Networks Functional Enrichment Analysis (STRING) was used to associate differentially expressed gene probes. According to the results, up to 10 mg/L concentration of TiB2 and Zn3BO6 NPs application did not stimulate a cytotoxic effect on the HPAEpiC cell cultures. Microarray analysis revealed that TiB2 NPs exposure enhances cellular adhesion molecules, proteases and carrier protein expression. Furthermore, Zn3BO6 NPs caused differential gene expressions in the cell cycle, cell division and extracellular matrix regulators. Finally, STRING analyses put forth that inflammation, cell regeneration and tissue repair-related gene interactions were affected by TiB2 NPs application. Zn3BO6 NPs exposure significantly altered inflammation, lipid metabolism and infection response activator-related gene interactions. These investigations illustrated that TiB2 and Zn3BO6 NPs exposure may affect different aspects of cellular machineries such as immunogenic responses, tissue regeneration and cell survival. Thus, these types of cellular mechanisms should be taken into account before the use of the related NPs in further biomedical applications.

Transcriptomic and metabolomics-based analysis of key biological pathways reveals the role of lipid metabolism in response to salt stress in the root system of Brassica napus

Transcriptomic and metabolomics-based analysis of key biological pathways reveals the role of lipid metabolism in response to salt stress in the root system of Brassica napus

Molecular cloning and structural characterization of PPARα gene from turbot ( Scophthalmus maximus ) and functional exploration of lipid metabolism in response to thermal stress

Peroxisome proliferator-activated receptor alpha (PPARα), as a transcription factor, plays an important role in the regulation of lipid metabolism. To better understand the regulatory role of PPARα in lipid metabolism in turbot, we analyzed the sequence structure of PPARα and its stress response to a high temperature. We also investigated the regulation of genes related to lipid metabolism after the knockdown of PPARα. The CDS of PPARα was 1410 bp, encoding 469 amino acids. The relative molecular weight of the protein was 52.64 kDa, and the predicted pI was 5.63. The architecture of the PPARα gene exhibited a ZnF-C4 domain and a HOLI domain. Phylogenetic analysis indicated that PPARα has been highly conserved during evolution. The qPCR results showed that the mRNA level of PPARα was significantly increased, and the expression of the lipid synthesis genes FASN and SCD was significantly downregulated under high-temperature stress. PPARα interference and inhibition results showed that the expression levels of FASN and SCD were significantly increased. Our results suggest that high temperatures activate PPARα and inhibit lipid synthesis by downregulating the expression of FASN and SCD in order to reduce lipid deposition and maintain lipid metabolism disorder caused by high-temperature stress. This is the first report of PPARα in turbot. It will help for studying the evolution of PPARα and provide a reliable reference for studying the regulation mechanism of lipid metabolism in fish under stress.

LCN2 Mediates Skin Inflammation in Psoriasis through the SREBP2‒NLRC4 Axis

Lipocalins are a family of secreted adipokines that regulate cell lipid metabolism and immune responses. Although we have previously revealed that LCN2 modulates neutrophil activation in psoriasis, the other roles of LCN2 in psoriatic local inflammation have remained elusive. In this study, we found that 24p3R, the well-known specific receptor of LCN2, was highly expressed in the lesional epidermis of patients with psoriasis. Silencing 24p3R (also known as slc22a17) alleviated hyperkeratosis, inflammatory cell infiltration, and overexpression of inflammatory mediators in an imiquimod-induced psoriasis-like mouse model. Invitro, LCN2 enhanced the expression of proinflammatory factors in primary keratinocytes, such as IL-1β, IL-23, CXCL1, and CXCL10, which was paralleled by enforced cholesterol biosynthetic signaling. Importantly, taking invivo and invitro approaches, we discovered the SREBP2, a vital transcriptional factor in cholesterol synthesis pathway, as the critical mediator of LCN2-induced keratinocyte activation, which bound to the promoter region of NLRC4. Suppressing SREBP2 in mice attenuated NLRC4 signaling and psoriasis-like dermatitis. Taken together, this study identifies the critical role of LCN2‒SREBP2‒NLRC4 axis in the pathogenesis of psoriasis and proposes 24p3R or SREBP2 as a potential therapeutic target for psoriasis.

PCSK9 and Inflammation: Their Role in Autoimmune Diseases, with a Focus on Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Despite a clear epidemiological link between autoimmune disease and cardiovascular (CV) risk exists, pathophysiological explanations are extremely complex and far from being elucidated. Dysregulation of metabolic pathways and chronic low-grade inflammation represent common pathways, but CV risk still remains underestimated in patients with autoimmune diseases. Among different candidate mediators, pro-protein convertase subtilisin/kexin type 9 (PCSK9) is attracting growing attention, due to a combined effect on lipid metabolism and inflammatory response. Studies on PCSK9 inhibitors have established a clear benefit on CV outcome without an established effect on inflammation. Conversely, evidence from sepsis and HIV infection strongly supports a pro-inflammatory role of PCSK9. Still, the role of PCSK9 in autoimmune diseases is uncertain. So far, reported clinical findings are controversial and likely reflect the poor knowledge of PCSK9 activity on monocyte/macrophage migration and activation. The complex signaling network around PCSK9 synthesis and metabolism may also have a role, especially concerning the involvement of scavenger receptors, such as CD36. Such complexity in PCSK9 signaling seems particularly evident in autoimmune disease model. This would also potentially explain the observed independency between lipid profile and PCSK9 levels, the so-called "lipid paradox". In this narrative review, we will summarize the current knowledge about the complex network of PCSK9 signaling. We will focus on upstream and downstream pathways with potential implication in autoimmune disease and potential effects of PCSK9 inhibiting strategies.

RNA Sequencing Analysis Reveals Divergent Adaptive Response to Hypo- and Hyper-Salinity in Greater Amberjack (Seriola dumerili) Juveniles.

Simple SummaryThe gill tanscriptomes of greater amberjack (Seriola dumerili) reared under different salinity stress were analyzed. The regulatory networks of salinity-related pathways were explored through Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment and bioinformatics analyses. This will be of great value in understanding the molecular basis of salinity adaptation in greater amberjack.Salinity significantly affects physiological and metabolic activities, breeding, development, survival, and growth of marine fish. The greater amberjack (Seriola dumerili) is a fast-growing species that has immensely contributed to global aquaculture diversification. However, the tolerance, adaptation, and molecular responses of greater amberjack to salinity are unclear. This study reared greater amberjack juveniles under different salinity stresses (40, 30, 20, and 10 ppt) for 30 days to assess their tolerance, adaptation, and molecular responses to salinity. RNA sequencing analysis of gill tissue was used to identify genes and biological processes involved in greater amberjack response to salinity stress at 40, 30, and 20 ppt. Eighteen differentially expressed genes (DEGs) (nine upregulated and nine downregulated) were identified in the 40 vs. 30 ppt group. Moreover, 417 DEGs (205 up-regulated and 212 down-regulated) were identified in the 20 vs. 30 ppt group. qPCR and transcriptomic analysis indicated that salinity stress affected the expression of genes involved in steroid biosynthesis (ebp, sqle, lss, dhcr7, dhcr24, and cyp51a1), lipid metabolism (msmo1, nsdhl, ogdh, and edar), ion transporters (slc25a48, slc37a4, slc44a4, and apq4), and immune response (wnt4 and tlr5). Furthermore, KEGG pathway enrichment analysis showed that the DEGs were enriched in steroid biosynthesis, lipids metabolism, cytokine–cytokine receptor interaction, tryptophan metabolism, and insulin signaling pathway. Therefore, this study provides insights into the molecular mechanisms of marine fish adaptation to salinity.

Responses of lipid metabolism and lipidomics in the hepatopancreas of Pacific white shrimp Litopenaeus vannamei to microcystin-LR exposure

Microcystin-LR (MC-LR) is a toxic substance that threatens the health of aquatic animals. Hepatopancreas is the target organ of MC-LR toxicity. In this study, we investigated the effects of MC-LR on hepatopancreas lipid metabolism and lipidomic responses in Litopenaeus vannamei. After MC-LR exposure for 72 h, the hepatopancreas showed obvious tissue damage, and the activities of several lipase isoenzymes were decreased. Furthermore, the relative gene expression levels of lipolysis (CPT1, AMPKα), lipogenesis (SREBP, FAS, ACC, 6PGD), and long-chain fatty acid β-oxidation (ACDL, ACDVL, ACBP) were increased. MC-LR exposure also affected lipidomics homeostasis. Specifically, the levels of glycerophospholipids (phosphatidylcholine, phosphatidic acid, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, lyso-phosphatidylglycerol), sphingolipids (sphingomyelin and ceramides) and cholesteryl ester were increased, and those of phosphatidylinositol and triglyceride were decreased. The significantly altered lipid molecules were mainly associated with the pathways of lipid and fatty acid metabolism and autophagy. These results reveal that MC-LR exposure influences lipid metabolism and lipidomic homeostasis in the shrimp hepatopancreas.

Study on Synergistic Antioxidant Effect of Typical Functional Components of Hydroethanolic Leaf Extract from Ginkgo Biloba In Vitro

The predicted anti-oxidation is related to apoptosis, proliferation, lipid metabolism, cell differentiation, and immune response. There are some differences in the antioxidant capacity of the four typical components of ginkgo biloba extract (EGb) including ginkgo flavone (GF), ginkgolide (G), procyanidins (OPC), and organic acids (OA), and any two members of them can exhibit apparent synergistic effects. The order of DPPH scavenging ability was: OPC > GF > OA > G. The scavenging ability of procyanidins was close to that of VC; the scavenging capacity of ABTS was GF > OPC > OA > G. The GF:OPC (1:9) showed the best synergism in scavenging DPPH and ABTS radicals. The 193 kinds of small molecules reported in EGb were obtained by analyzing the properties of EGb. In order to construct a corresponding biological activity target set, molecular docking and the network pharmacology method were employed to build the molecular action mechanism network of a compound target, and the main biological functions and signaling pathways involved with their antioxidant activities were predicted. The results displayed that the top ten compounds which belonged to the two broad categories, ginkgo flavonoids and proanthocyanidins, could interact closely with several important target proteins (CASP3, SOD2, MAPK1, HSPA4, and NQO1). This would be expected to lay a theoretical foundation for the deep development of Ginkgo biloba extract.

Folic Acid Attenuates High-Fat Diet-Induced Osteoporosis Through the AMPK Signaling Pathway.

Objective: Obesity caused by a high-fat diet (HFD) will expand adipose tissue and cause chronic low-grade systemic inflammation, leading to osteoporosis. Folic acid (FA) is a water-soluble vitamin that plays an essential role in regulating blood lipids and antioxidants. However, the effects and underlying mechanisms of FA in osteoporosis induced by an HFD remain poorly understood. This study aimed to investigate the effect of FA on bone health by using HFD-induced osteoporosis mice. Materials and Methods: Mice were fed a normal diet, HFD or an HFD supplemented with FA (20 μg/ml in drinking water) for 16 weeks. Throughout the 16 weeks study period, the rats were weighed once every week. GTT, ITT and lipid indexes were detected to evaluate the effects of FA on lipid metabolism in the HFD-fed mice. Morphological and structural changes of the femur and tibial bone were observed using micro-CT, HE staining and bone conversion parameters. The expression of MDA, SOD and inflammatory factors were detected to evaluate the effects of FA on oxidative stress and inflammatory response in the HFD-fed mice. Quantitative real-time PCR and Western blot (WB) were used to investigate the AMPK signaling pathway. Results: After the intervention of FA, the body fat rate of obese mice was reduced, and related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation were alleviated. In correlation with those modifications, FA attenuated bone loss and improved bone microarchitecture, accompanied the number of osteoclasts and adipocytes decreased. Furthermore, FA promoted the phosphorylation of AMPK, thereby promoting the expression of Carnitine palmitoyltransferase 1 (CPT1), nuclear factor erythroid-2 related factor 2 (Nrf2) and antioxidant enzymes. Conclusion: These findings suggest that FA may modulate lipid metabolism and oxidative stress responses activating the AMPK signaling pathway, thereby alleviating HFD-induced osteoporosis. The results from our study provide experimental evidence to prevent HFD-induced osteoporosis.

Transcriptomic Analysis of the Tolerance Response to Dehydration and Rehydration in Wheat Seedlings

Drought is the main abiotic stress that restricts wheat production. The rapid development of sequencing technology and its widespread application to various fields have revealed the structural characteristics and regulation of related genes through gene expression analysis. Here, we studied responses of wheat plants under drought and re-watering conditions, using morphological and physiological indicators. Moreover, a transcriptome analysis was conducted on Jingmai 12, a drought-resistant wheat strain, to explore the mechanism underlying the response of drought-resistant wheat seedlings to drought stress at the transcriptome level. Drought stress caused morphological and physiological changes in both drought-resistant and -sensitive varieties, but to a greater extent in the drought-sensitive specimen. After re-watering, the drought-resistant wheat showed greater ability to recover than the drought-sensitive wheat. Transcriptome sequencing of Jingmai 12 revealed 97,422 genes, including 80,373 known genes and 17,049 newly predicted genes. The observed upregulation of genes was mostly involved in hormone and signal transduction, carbon metabolism, amino acid synthesis, small molecule production, transmembrane transport, ROS detoxification and defense, drought response protein, and protective enzyme activity. Downregulated genes were mostly involved in photosynthesis, lipid metabolism, signaling, and auxin response. Upon rehydration, these genes and metabolic pathways returned to normal. Our results suggest that all these changes are adaptations to drought stress. Through morphological adaptation, physiological regulation, and the expression of drought-induced genes, normal growth of drought-resistant varieties under drought stress can be promoted. These results increase our understanding of the transcriptomic changes taking place in drought-resistant wheat seedlings under drought stress, and provide a direction for future investigations.

Sanghuangporus vaninii mixture ameliorated type 2 diabetes mellitus and altered intestinal microbiota in mice.

Type 2 diabetes mellitus (T2DM) is a chronic disease mainly caused by insufficient insulin secretion and insulin resistance. In addition, T2DM is often accompanied by dysregulation of lipid metabolism and inflammatory response. The effect of oral administration of a Sanghuangporus vaninii mixture (SVM) on T2DM mice was evaluated. The results showed that SVM intervention could change body weight and glucose/lipid metabolism-related indicators. In addition, it can also improve the level of inflammatory factors to play a protective role in the pancreas and the jejunum. 16S rRNA gene sequencing analysis indicated that SVM intervention significantly altered the intestinal microbiota in mice, elevating the relative abundances of Bacteroidetes, Verrucomicrobia, Akkermansia, Alloprevotella, and Blautia, and decreasing the relative abundances of Firmicutes, Lactobacillus, Flavonifractor, and Odoribacter in the feces of diabetic mice, compared with the model group. Moreover, the functional modules of fatty acid degradation, glycerolipid metabolism, purine metabolism, histidine metabolism, folate biosynthesis, GABAergic synapse, etc. were regulated by SVM intervention in T2DM mice. Additionally, integrative correlation analysis revealed that the representative intestinal microbes in response to SVM intervention in diabetic mice were markedly related to glucose/lipid metabolism-related indicators (e.g. blood glucose, insulin resistance, lipid indexes, and inflammatory factors). Hence, these findings suggest that the SVM could modulate the structure, abundance, and function of intestinal microbiota to potentially ameliorate T2DM and its complications (e.g. hyperglycemia, hyperlipidemia, and inflammation) in mice.

Systematic analysis and comparison of ABC proteins superfamily confer structural, functional and evolutionary insights into four cotton species

ATP binding cassette transporters (ABCTs) is one of the largest gene superfamily comprising of integral membrane proteins that are ubiquitously found in all domains of life and implicated in ATP dependent active transport of ligands across the concentration gradient. We present here the identification and distribution of ABC proteins from seven plant species into four groups (Full, Half, Quarter and ABC2 molecules), eight families (ABCA to ABCG and ABCI) and twelve sub families (MDR, PDR, MRP, PMP, AOH, ATH, ATM, TAP, WBC, RLI, GCN and NAP) based on topology, orientation, size, and phylogenetic relationships with main focus on four cotton species especially tetraploid Gossypium hirsutum (Gh) encoding 320 ORFs. Dynamics of complex formation of structurally characterized ABCTs from each subfamily shows their kinetic and molecular mechanisms to combine the ATP hydrolysis and binding for substrate translocation, portraying a "structure to function relationship". Analysis of protein motif and genomic organizations displayed structural and functional conservation within same subfamily but diverged among the different subfamilies. Abundance of small sized single ABCs signifies the higher gene death/birth rate and ongoing evolution for functional advancements and environmental adaptability. Gene duplication relationship analysis illustrates the major role of tandem and segmental duplication in large scale expansion of ABC gene family in mentioned species. The overall Ka/Ks ratio indicated the intense purifying selection of ABC genes in four cotton species during evolution. In addition, tissue specific expression profiling, abiotic stress resistance and Co-expression networking of GhABCs infers their role in diverse range of molecular, cellular and biological processes. Cis-elements and gene enrichments also supported their predicted roles in substrates translocation, xenobiotic detoxification, lipid metabolism, hormonal and abiotic stresses responses. Forward and reverse genetics along with evolutionary trajectories, structural dynamics and validated expression profiling will provide much-needed clarity and a qualitative molecular framework for future research. This study will further broaden our insights into the evolution and functional elucidation of ABC gene family in cotton.

Nrf2 plays a critical role in the metabolic response during and after spaceflight

Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by Nrf2 knockout. We conducted metabolome analyses of plasma from wild-type and Nrf2 knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in Nrf2 knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of Nrf2 knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.

Exploring the Therapeutic Mechanisms of Huzhang-Shanzha Herb Pair against Coronary Heart Disease by Network Pharmacology and Molecular Docking.

Background Coronary heart disease (CHD) seriously affects human health, and its pathogenesis is closely related to atherosclerosis. The Huzhang (the root of Polygonum cuspidatum)–Shanzha (the fruit of Crataegus sp.), a classic herb pair, has been widely used for the treatment of CHD. In recent years, Huzhang–Shanzha herb pair (HSHP) was found to have a wide range of effects in CHD; however, its therapeutic specific mechanisms remain to be further explored. The aim of this study was to elucidate the molecular mechanism of HSHP in the treatment of CHD using a network pharmacology analysis approach. Methods The Batman-TCM database was used to explore bioactive compounds and corresponding targets of HSHP. CHD disease targets were extracted from Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Then, the protein-protein interaction (PPI) network was constructed using the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Finally, molecular docking of the active components was assessed to verify the potential targets of HSHP to treat CHD by the AutoDock Vina and PyMOL software. Results Totally, 243 active components and 2459 corresponding targets of LDP were screened out. Eighty-five common targets of HSHP and CHD were identified. The results of the network analysis showed that resveratrol, anthranone, emodin, and ursolic acid could be defined as four therapeutic components. TNF, ESR1, NFКB1, PPARG, INS, TP53, NFКBIA, AR, PIK3R1, PIK3CA, PTGS2, and NR3C1 might be the 12 key targets. These targets were mainly involved in the regulation of biological processes, such as inflammatory responses and lipid metabolism. Enrichment analysis showed that the identified genes were mainly involved in fluid shear force, insulin resistance (IR), inflammation, and lipid metabolism pathways to contribute to CHD. This suggests that resveratrol, anthranone, emodin, and ursolic acid from HSHP can be the main therapeutic components of atherosclerosis. Conclusion Using network pharmacology, we provide new clues on the potential mechanism of action of HSHP in the treatment of CHD, which may be closely related to the fluid shear force, lipid metabolism, and inflammatory response.

Network Pharmacology-Based Analysis of Pogostemon cablin (Blanco) Benth Beneficial Effects to Alleviate Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.

Effects of allyl isothiocyanate on the expression, function, and its mechanism of ABCA1 and ABCG1 in pulmonary of COPD rats

Background and aimsAllyl isothiocyanate(AITC) has been shown to play an important role in the improved symptoms of chronic obstructive pulmonary disease(COPD) and the inhibition of inflammation, but the role in COPD lipid metabolism disorder and the molecular mechanism remains unclear. We aimed to explore whether and how AITC affects COPD by regulating lipid metabolism and inflammatory response. MethodsThe COPD rat model was established by cigarette smoke exposure. Cigarette smoke extract stimulated 16HBE cells to induce a cell model. The effect of AITC treatment was detected by lung function test, H&E staining, Oil red O staining, immunohistochemistry, ELISA, CCK-8, HPLC, fluorescence efflux test, siRNA, RT-PCR, and Western blotting. Biological analysis was performed to analyze the results. Graphpad Prism 8.0 software was used for statistical analysis. ResultsAITC can improve lung function and pathological injury in COPD rats. The levels of IL-1 β and TNF- α in the AITC treatment group were significantly lower than those in the model group(P < 0.05), and the lipid metabolism was also improved (P < 0.05). AITC reverses CSE-induced down-regulation of LXR α, ABCA1, and ABCG1 expression and function in a time-and concentration-dependent manner (P < 0.05). AITC regulates the cholesterol metabolism disorder induced by CSE in NR8383 cells and attenuates macrophage inflammation (P < 0.05). In addition, after silencing LXR α with siRNA, the effect of AITC was also inhibited. ConclusionThese results suggest that AITC improves COPD by promoting RCT process and reducing inflammatory response via activating LXR pathways.

Transcriptomic survey reveals multiple adaptation mechanisms in response to nitrogen deprivation in marine Porphyridium cruentum.

Single-cell red microalga Porphyridium cruentum is potentially considered to be the bioresource for biofuel and pharmaceutical production. Nitrogen is a kind of nutrient component for photosynthetic P. cruentum. Meanwhile, nitrogen stress could induce to accumulate some substances such as lipid and phycoerythrin and affect its growth and physiology. However, how marine microalga Porphyridium cruentum respond and adapt to nitrogen starvation remains elusive. Here, acclimation of the metabolic reprogramming to changes in the nutrient environment was studied by high-throughput mRNA sequencing in the unicellular red alga P. cruentum. Firstly, to reveal transcriptional regulation, de novo transcriptome was assembled and 8,244 unigenes were annotated based on different database. Secondly, under nitrogen deprivation, 2100 unigenes displayed differential expression (1134 upregulation and 966 downregulation, respectively) and some pathways including carbon/nitrogen metabolism, photosynthesis, and lipid metabolism would be reprogrammed in P. cruentum. The result demonstrated that nitrate assimilation (with related unigenes of 8–493 fold upregulation) would be strengthen and photosynthesis (with related unigenes of 6–35 fold downregulation) be impaired under nitrogen deprivation. Importantly, compared to other green algae, red microalga P. cruentum presented a different expression pattern of lipid metabolism in response to nitrogen stress. These observations will also provide novel insight for understanding adaption mechanisms and potential targets for metabolic engineering and synthetic biology in P. cruentum.