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Background: Hepatocellular carcinoma (HCC) with complex molecular carcinogenesis represents a kind of prevalent neoplasm occurring in the liver. The objective of this study is to illustrate the function of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and underlying action mechanisms in HCC progression. Methods: Comprehensive bioinformatics methods were conducted to screen differentially expressed genes (DEGs), cuproptosis-associated DEGs, and hub genes. The correlation between BIRC5 and immune cell infiltration, prognosis value was evaluated. The specific effects of BIRC5 silencing on HCC cells was validated by functional assays, and the impact on tumorigenicity and cuproptosis was also elucidated in vivo. Additionally, the effects of BIRC5 deficiency on PPAR pathway were determined using Oroxin A in vitro. Results: A total of 45 cuproptosis-associated DEGs and 9 hub genes were discovered through bioinformatics. Then 6 core genes were confirmed in Hep-3B and SK-Hep-1 cells with 4 genes upregulated and 2 genes downregulated. Therein, BIRC5 was positively correlated with the infiltration of CD8+ T cells, macrophages, and highly expressed BIRC5 exhibited poor prognosis of overall survival in HCC. Furthermore, BIRC5 deletion inhibited the PPARγ pathway, thereby restraining the malignant phenotypes of HCC cells and tumorigenesis in vivo. Additionally, silencing of BIRC5 contributed to the initiation of cuproptosis in HCC. Conclusions: BIRC5 silencing attenuated HCC through blocking PPARγ pathway and regulating cuproptosis, which may offer therapeutic implications against HCC. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) with complex molecular carcinogenesis represents a kind of prevalent neoplasm occurring in the liver. The objective of this study is to illustrate the function of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and underlying action mechanisms in HCC progression. Methods Comprehensive bioinformatics methods were conducted to screen differentially expressed genes (DEGs), cuproptosis-associated DEGs, and hub genes. The correlation between BIRC5 and immune cell infiltration, prognosis value was evaluated. The specific effects of BIRC5 silencing on HCC cells was validated by functional assays, and the impact on tumorigenicity and cuproptosis was also elucidated in vivo. Additionally, the effects of BIRC5 deficiency on PPAR pathway were determined using Oroxin A in vitro. Results A total of 45 cuproptosis-associated DEGs and 9 hub genes were discovered through bioinformatics. Then 6 core genes were confirmed in Hep-3B and SK-Hep-1 cells with 4 genes upregulated and 2 genes downregulated. Therein, BIRC5 was positively correlated with the infiltration of CD8+ T cells, macrophages, and highly expressed BIRC5 exhibited poor prognosis of overall survival in HCC. Furthermore, BIRC5 deletion inhibited the PPARγ pathway, thereby restraining the malignant phenotypes of HCC cells and tumorigenesis in vivo. Additionally, silencing of BIRC5 contributed to the initiation of cuproptosis in HCC. Conclusions BIRC5 silencing attenuated HCC through blocking PPARγ pathway and regulating cuproptosis, which may offer therapeutic implications against HCC.

Aim: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague–Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. Methods: Gait analysis and Y‐maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. Results: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. Conclusion: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP. [ABSTRACT FROM AUTHOR]

Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as "PPAR signaling pathway", "tyrosine metabolism", "nonalcoholic fatty liver disease (NAFLD) pathway", "melanogenesis", and "IL-17 signaling pathway". Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a global public health concern. A synbiotic preparation containing Bifidobacterium lactis and Lactobacillus acidophilus has been used as adjunct therapy for hypertension. We sought to elucidate the antihypertensive activity of this preparation and explore the underlying mechanisms. Methods and results: Blood pressure in rats was measured using the tail-cuff method. Colonization of the gastrointestinal tract by the two probiotics was determined by real-time quantitative polymerase chain reaction (qPCR). Mechanistic studies were performed by proteomic analyses based on liquid chromatography-mass spectrometry and STRING database and metabolomic analyses using the UHPLC-Q-TOF/MS platform and peroxisome proliferator-activated receptor (PPAR)β/γ antagonists. Although biochemical analysis of blood samples showed that the synbiotic preparation did not alter the levels of angiotensin II, aldosterone, or cortisol, it significantly lowered the systolic blood pressure in the treatment group. Moreover, the synbiotic preparation contributed to the localization of the two probiotics in the ileum and colon of the treatment group. Proteomics, immunochemistry, and real-time qPCR analyses showed that administration of the synbiotic preparation activated the PPAR signaling pathway in the ileum and significantly upregulated PPARβ and PPARγ. The antagonist studies further confirmed this finding. In addition, metabolomic analyses demonstrated that among the 27 metabolites that showed significant differences between the control and model groups, administration of the synbiotic preparation significantly upregulated lysophosphatidylethanolamine and phosphatidylcholine in the ileum of the treatment group. Conclusion: The results of the study suggest that the novel synbiotic preparation reduces blood pressure by altering the composition of the intestinal microbiota, regulating PPAR signaling pathway, and activating the PPARβ and PPARγ cascade reactions in the ileum.

Abstract Background Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. Methods Hub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague–Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin–eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1β. Results Six hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1β-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1β-induced chondrocytes. Conclusion PDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management.

To investigate the regulatory mechanism of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD). The murine model was established by HFD or HFD combined with DHA-PS (100 mg/kg) administration for 10 weeks. DHA-PS administration notably improved HFD-induced abnormalities of liver function, lipid indices, inflammatory markers, and oxidative stress. In addition, based on non-targeted metabolomics, HFD notably disrupted the amino acid metabolism and fatty acid metabolism in murine liver tissue, while DHA-PS notably regulated the amino acid metabolism and PPAR signaling pathway to alleviate HFD-induced liver metabolic disorder. Moreover, results from Western blot and immunohistochemical analysis confirmed that DHA-PS alleviated HFD-induced NAFLD by regulating lipid metabolism and restraining the TLR4/NF-κB pathway. The results obtained suggest that DHA-PS might be used as a potential dietary supplement for alleviating HFD-induced NAFLD. [Display omitted] • Metabolomics elucidates the mechanism of DHA-enriched phosphatidylserine (DHA-PS). • DHA-PS regulates amino acid and lipid metabolism. • DHA-PS restrains toll-like receptor/nuclear factor kappa B pathway. [ABSTRACT FROM AUTHOR]

• Little variance exists between six cultivars of sunflower seeds in terms of chemical profile and abundance. • PPAR signaling pathway is mostly induce by the metabolites of sunflower seeds for its antidiabetic effect. • MMP1 and PPARA genes of the PPAR pathways is mostly modulated by the metabolites of sunflower seeds for its antidiabetic effect. • Metabolites of sunflower seeds had better affinity for MMPI gene than PPARA gene in the antidiabetic modulation of PPAR pathway. • CGA, CFG, and GPA are the active metabolites in sunflower seeds responsible for its antidiabetic effects. Helianthus annuus cypsela (sunflower) is a staple oilseed crop with significant therapeutic applications against diverse diseases including type 2 diabetes mellitus (T2DM). Despite its reported antidiabetic potential, the implicated molecular mechanism of action is yet to be unravelled to date. This study evaluated the molecular mechanism of the antidiabetic activity of sunflower cypsela using network pharmacology (NP), density functional theory, and molecular dynamics (MD) simulation approaches. The six cultivars of sunflower cypsela used were profiled for their secondary metabolites using LC-MS and GC–MS techniques. Subsequently, the genes associated with the identified metabolites were screened against T2DM-associated genes using NP. Based on the KEGG enrichment analysis of the identified common genes, signaling pathways were subsequently identified. The results obtained revealed 87 intersecting genes between the metabolites of sunflower cypsela and T2DM, while the KEGG analysis identified 35 signaling pathways with the PPAR route and its associated genes as the most implicated in T2DM progression with respect to sunflower cypsela. Both MMP1 and PPARA in the PPAR pathways interacted most with the identified metabolites, with CGA (−43.74 kcal/mol), GPA (−41.62 kcal/mol), and CFG (−45.36 kcal/mol) having higher binding free energy than both ROS and MET (reference standards) against MMP1 after 100,000 ps MD simulation. In contrast, ROS (−46.98 kcal/mol) had better affinity against PPARA compared to the top hits of sunflower cypsela. However, against both gene targets, the top hits had significant thermodynamic stability, flexibility, and compactness, which are attributable to their bond interactions and molecular orbital properties. These findings are suggestive of the essential role of the top-hits in the antidiabetic potential of sunflower cypsela through activation of the PPAR signalling pathway and most especially MMP1. In this regard, the modulation of MMP1 and PPARA genes by the identified metabolites of sunflower cypsela may enhance insulin sensitivity and glucose homoeostasis in the management of T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Temperature plays a crucial role in the growth and development of fish, particularly during the early stages. This study aimed to investigate the effects of different breeding temperatures (21, 24, 27, and 30 °C) on the growth and nutrient metabolism of Platax teira larvae using transcriptomic techniques. The analysis revealed differentially expressed genes (DEGs) associated with various biological processes, such as metabolism, catalytic activity, and cellular processes. Pathway analysis showed enrichment in metabolic pathways, including matter and energy metabolism, protein digestion and absorption, and glucose and lipid metabolism. The study also observed that gene expression related to energy, lipid, and glucose metabolism was upregulated at lower temperatures (21 °C), while extremely high temperatures (30 °C) led to suppressed nutrient metabolism and growth due to oxidative stress. These findings highlight the involvement of nutrient metabolism pathways in the thermal stress response of P. teira, with an optimal breeding temperature range of 24–27 °C. This study contributes to our understanding of the regulatory mechanisms of larval development under different growth temperatures, providing insights for industrial breeding practices. The growth, development, and survival of fish, especially in the early stages of development, is influenced by a complex of environmental factors, among which temperature is one of the most important. Although the physiological effects of environmental stress in fish have been extensively studied, the molecular mechanisms are poorly understood. However, recent advances in transcriptomic techniques have facilitated the study of the molecular mechanisms of environmental stress responses in aquatic species. Here, we aimed to elucidate the effects of breeding temperatures (21, 24, 27, and 30 °C) on the growth and nutrient metabolism in the early developmental stage of Platax teira, using transcriptomic techniques. Transcriptomic analysis identified 5492, 6937, and 4246 differentially expressed genes (DEGs) in the 21 vs. 24 °C, 27 vs. 24 °C, and 30 vs. 24 °C comparisons, respectively, most of which were involved in cell processes, single organism, metabolism, catalytic activity, and cell part, based on gene ontology (GO) functional annotations. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were mainly enriched in pathways related to metabolism of matter and energy, protein digestion and absorption, and glucose and lipid metabolism. Additionally, the expression of genes related to energy, lipid, and glucose metabolism in the fish liver was upregulated under a low-temperature condition (21 °C), although increasing the temperature within the acceptable threshold improved nutrient metabolism and growth in the fish. Meanwhile, nutrient metabolism and growth were suppressed by an extremely high temperature (30 °C) owing to oxidative stress. Overall, it was shown that nutrient metabolism pathways were involved in thermal stress responses in P. teira, and the optimal breeding temperature range was 24–27 °C. Through transcriptomics, the regulatory mechanism of larval development in P. teira under different growth temperatures was elucidated, with the goal of establishing a theoretical basis for industrial breeding. [ABSTRACT FROM AUTHOR]

The fruit of Phyllanthus emblica (PE) is a 'drug homologous food' that is rich in polyphenols for treating inflammatory diseases. Nevertheless, the ability of PE polyphenols (PEP) to alleviate ulcerative colitis (UC) remains unclear. The aim of this study was to reveal the chemical composition of PEP and its therapeutic potential for treating UC. In this study, PEP was purified with an NKA-2 macroporous resin and identified via liquid chromatography combined with mass spectrometry (LC‒MS). Furthermore, a dextran sulfate sodium salt-induced UC mice model was used to evaluate the ability of PEP to alleviate UC. The symptoms, histopathology, expression of inflammatory cytokines, mucus and tight junction levels, changes in the gut microbiome and colon transcriptomics of UC mice were assessed after PEP intervention. The results suggested that PEP strikingly improved weight loss, disease activity index scores, colon length changes and histopathological damage. Moreover, PEP inhibited the expression of serum proinflammatory cytokines (TNF- α , IL-1 β , and IL-6) and sustained intestinal integrity by increasing the expression of Mucin 2, Zonula occludens 1 and Occludin. 16S rRNA sequencing revealed that PEP regulated disorders of the gut microflora related to inflammation and the mucus barrier, including Escherichia_Shigella , Rikenellaceae _RC9_gut_group , Bacteroides , Muribaculaceae , Helicobacter and Anaerostipes. Transcriptome sequencing analysis, western blotting, and immunohistochemistry confirmed that PEP regulated reversed genes as well as effector proteins enriched in the PPAR signaling pathway (PPAR γ , MMP1, CYP4A12A, and UCP1) and the Wnt/ β -catenin signaling pathway (Wnt8B, FZD9, GSK3 β , p -GSK3 β , β -catenin, Axin2 and Lgr5). These findings indicate that PEP has therapeutic potential for alleviating UC and could serve as a functional dietary supplement. [Display omitted] • Phyllanthus emblica polyphenol (PEP) improved the symptoms of ulcerative colitis (UC) mice. • PEP ameliorated UC though controlling the inflammatory response and regulating the intestinal microbial homeostasis. • PEP remodeled the intestinal barrier function of UC mice via activating the Wnt/ β -catenin signaling pathway. [ABSTRACT FROM AUTHOR]

The growth, development, and survival of fish, especially in the early stages of development, is influenced by a complex of environmental factors, among which temperature is one of the most important. Although the physiological effects of environmental stress in fish have been extensively studied, the molecular mechanisms are poorly understood. However, recent advances in transcriptomic techniques have facilitated the study of the molecular mechanisms of environmental stress responses in aquatic species. Here, we aimed to elucidate the effects of breeding temperatures (21, 24, 27, and 30 °C) on the growth and nutrient metabolism in the early developmental stage of Platax teira, using transcriptomic techniques. Transcriptomic analysis identified 5492, 6937, and 4246 differentially expressed genes (DEGs) in the 21 vs. 24 °C, 27 vs. 24 °C, and 30 vs. 24 °C comparisons, respectively, most of which were involved in cell processes, single organism, metabolism, catalytic activity, and cell part, based on gene ontology (GO) functional annotations. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were mainly enriched in pathways related to metabolism of matter and energy, protein digestion and absorption, and glucose and lipid metabolism. Additionally, the expression of genes related to energy, lipid, and glucose metabolism in the fish liver was upregulated under a low-temperature condition (21 °C), although increasing the temperature within the acceptable threshold improved nutrient metabolism and growth in the fish. Meanwhile, nutrient metabolism and growth were suppressed by an extremely high temperature (30 °C) owing to oxidative stress. Overall, it was shown that nutrient metabolism pathways were involved in thermal stress responses in P. teira, and the optimal breeding temperature range was 24–27 °C. Through transcriptomics, the regulatory mechanism of larval development in P. teira under different growth temperatures was elucidated, with the goal of establishing a theoretical basis for industrial breeding.

Xiaozhi formula (XZF) is a practical Chinese herbal formula for the treatment of non-alcoholic fatty liver disease (NAFLD), which possesses an authorized patent certificate issued by the State Intellectual Property Office of China (ZL202211392355.0). However, the underlying mechanism by which XZF treats NAFLD remains unclear. This study aimed to explore the main component of XZF and its mechanism of action in NAFLD treatment. UHPLC-Q-Orbitrap HRMS was used to identify the components of the XZF. A high-fat diet (HFD)-induced NAFLD mouse model was used to demonstrate the effectiveness of XZF. Body weight, liver weight, and white fat weight were recorded to evaluate the therapeutic efficacy of XZF. H&E and Oil Red O staining were applied to observe the extent of hepatic steatosis. Liver damage, lipid metabolism, and glucose metabolism were detected by relevant assay kits. Moreover, the intraperitoneal insulin tolerance test and the intraperitoneal glucose tolerance test were employed to evaluate the efficacy of XZF in insulin homeostasis. Hepatocyte oxidative damage markers were detected to assess the efficacy of XZF in preventing oxidative stress. Label-free proteomics was used to investigate the underlying mechanism of XZF in NAFLD. RT-qPCR was used to calculate the expression levels of lipid metabolism genes. Western blot analysis was applied to detect the hepatic protein expression of AMPK, p-AMPK, PPARɑ, CPT1, and PPARγ. 120 compounds were preliminarily identified from XZF by UHPLC-Q-Orbitrap HRMS. XZF could alleviate HFD-induced obesity, white adipocyte size, lipid accumulation, and hepatic steatosis in mice. Additionally, XZF could normalize glucose levels, improve glucolipid metabolism disorders, and prevent oxidative stress damage induced by HFD. Furthermore, the proteomic analysis showed that the major pathways in fatty acid metabolism and the PPAR signaling pathway were significantly impacted by XZF treatment. The expression levels of several lipolytic and β-oxidation genes were up-regulated, while the expression of fatty acid synthesis genes declined in the HFD + XZF group. Mechanically, XZF treatment enhanced the expression of p-AMPK, PPARɑ, and CPT-1 and suppressed the expression of PPARγ in the livers of NAFLD mice, indicating that XZF could activate the AMPK and PPAR pathways to attenuate NALFD progression. XZF could attenuate NAFLD by moderating lipid metabolism by activating AMPK and PPAR signaling pathways. [Display omitted] • Provided a TCM therapeutic method for NAFLD. • The mechanism of XZF relies on regulating lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a global public health concern. A synbiotic preparation containing Bifidobacterium lactis and Lactobacillus acidophilus has been used as adjunct therapy for hypertension. We sought to elucidate the antihypertensive activity of this preparation and explore the underlying mechanisms., Methods and Results: Blood pressure in rats was measured using the tail-cuff method. Colonization of the gastrointestinal tract by the two probiotics was determined by real-time quantitative polymerase chain reaction (qPCR). Mechanistic studies were performed by proteomic analyses based on liquid chromatography-mass spectrometry and STRING database and metabolomic analyses using the UHPLC-Q-TOF/MS platform and peroxisome proliferator-activated receptor (PPAR)β/γ antagonists. Although biochemical analysis of blood samples showed that the synbiotic preparation did not alter the levels of angiotensin II, aldosterone, or cortisol, it significantly lowered the systolic blood pressure in the treatment group. Moreover, the synbiotic preparation contributed to the localization of the two probiotics in the ileum and colon of the treatment group. Proteomics, immunochemistry, and real-time qPCR analyses showed that administration of the synbiotic preparation activated the PPAR signaling pathway in the ileum and significantly upregulated PPARβ and PPARγ. The antagonist studies further confirmed this finding. In addition, metabolomic analyses demonstrated that among the 27 metabolites that showed significant differences between the control and model groups, administration of the synbiotic preparation significantly upregulated lysophosphatidylethanolamine and phosphatidylcholine in the ileum of the treatment group., Conclusion: The results of the study suggest that the novel synbiotic preparation reduces blood pressure by altering the composition of the intestinal microbiota, regulating PPAR signaling pathway, and activating the PPARβ and PPARγ cascade reactions in the ileum., Competing Interests: It is the first time to submit the research article to Heliyon. This manuscript is based on the original research results and has never been published elsewhere. We warrant that all of the authors have contributed substantially to the manuscript and approved the final submission. If accepted, it will not be published elsewhere in the same form, in English or in any other language., (© 2024 The Authors.)

Diabetic nephropathy (DN) is one of the most important comorbidities for diabetic patients, which is the main factor leading to end-stage renal disease. Heparin analogs can delay the progression of DN, but the mechanism is not fully understood. In this study, we found that low molecular weight heparin therapy significantly upregulated some downstream proteins of the peroxisome proliferator-activated receptor (PPAR) signaling pathway by label-free quantification of the mouse kidney proteome. Through cell model verification, low molecular weight heparin can protect the heparan sulfate of renal tubular epithelial cells from being degraded by heparanase that is highly expressed in a high-glucose environment, enhance the endocytic recruitment of fatty acid-binding protein 1, a coactivator of the PPAR pathway, and then regulate the activation level of intracellular PPAR. In addition, we have elucidated for the first time the molecular mechanism of heparan sulfate and fatty acid-binding protein 1 interaction. These findings provide new insights into understanding the role of heparin in the pathogenesis of DN and developing corresponding treatments., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Selenium (Se) deficiency and poor plasma Se levels can cause cardiovascular diseases by decreasing selenoprotein levels. Neutrophil extracellular traps (NETs) may be the vicious cycle center of inflammation in vasculitis. Here, we show that Se deficiency induced arteritis mainly by reducing selenoprotein S (SelS), and promoted the progression of arteritis by regulating the recruitment of neutrophils and NET formation. Silencing SelS induced chicken arterial endothelial cells (PAECs) to secrete cytokines, and activated neutrophils to promote NET formation. Conversely, scavenging DNA-NETs promoted cytokine secretion in PAECs. The NET formation regulated by siSelS was dependent on a reactive oxygen species (ROS) burst. We also found that the PPAR pathway was a major mediator of NET formation induced by Se-deficient arteritis. Overall, our results reveal how Se deficiency regulates NET formation in the progression of arteritis and support silencing-SelS worsens arteritis.

Previously, we demonstrated that exposure to some diortho-phthalate esters during sexual differentiation disrupts male reproductive development by reducing fetal rat testis testosterone production (T Prod) and gene expression in a dose-related manner. The objectives of the current project were to expand the number of test compounds that might reduce fetal T Prod, including phthalates, phthalate alternatives, pesticides, and drugs, and to compare reductions in T Prod with altered testis mRNA expression. We found that PEs that disrupt T Prod also reduced expression of a unique "cluster" of mRNAs for about 35 genes related to sterol transport, testosterone and insulin-like hormone 3 hormone syntheses, and lipoprotein signaling and cholesterol synthesis. However, phthalates had little or no effect on mRNA expression of genes in peroxisome proliferator-activated receptor (PPAR) pathways in the fetal liver, whereas the 3 PPAR agonists induced the expression of mRNA for multiple fetal liver PPAR pathway genes without reducing testis T Prod. In summary, phthalates that disrupt T Prod act via a novel adverse outcome pathway including down regulation of mRNA for genes involved in fetal endocrine function and cholesterol synthesis and metabolism. This profile was not displayed by PEs that did not reduce T Prod, PPAR agonists or the other chemicals. Reductions in fetal testis gene expression and T Prod in utero can be used to establish relative potency factors that can be used quantitatively to predict the doses of individual PEs and mixtures of phthalates that produce adverse reproductive tract effects in male offspring. [ABSTRACT FROM AUTHOR]

Abstract Background Caponization results in reduced androgen levels, which leads to abdominal fat accumulation in capons. In this study, we sought to understand the molecular mechanisms behind this fat accumulation. Results Abdominal fat (AF) content increased significantly (P

Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as " f25 " was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC 50 = 7.70 ± 0.58 μΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-β, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies. [Display omitted] • f25 exhibits high cytotoxicity against tongue squamous cell carcinoma cell line CAL-27 cells. • f25 significantly inhibited the migration and invasion of CAL-27 cells and promoted apoptosis. • f25 acts on CAL-27 cells by activating the PPAR signalling pathway thereby exerting an anti-tumour effect. • f25 inhibits tumour growth in a nude mouse model and has a high biosafety profile. [ABSTRACT FROM AUTHOR]

Anti-obesity effect of chito-oligosaccharides (CO), resistant starch (RS) and their complexes (CO-RS) was investigated using high-fat fed rats. All of three intervention groups showed anti-obesity effect in the following order: CO-RS > CO > RS. This study revealed CO-RS administration achieved the lightest body weight, the lowest liver weight/index and the highest level of total antioxidant capacity in serum. The RNA sequencing data indicated that peroxisome proliferator-activated receptor (PPAR) pathway was significantly enriched by CO-RS administration. Among the genes involved in PPAR pathway, changes in the expression of Cyp7a1 gene were noticed, indicating an accelerated conversion of cholesterol into bile acids. Furthermore, the current study also revealed that, compared to the high-fat diet control, intervention with CO-RS led to significant reduction in mRNA expression of insulin-induced genes (Insig-1), which did not occur in other two interventions, suggesting a different regulatory pathway affecting lipids metabolism compared with either CO or RS.

RNA-Seq, a new developing high-throughput sequencing technology in recent years, provides a new and more effective method for research in the genes' expression. The technology has been used to further improve our understanding on the function of the gene structure information and excavate the new transcripts and new genes. In this study, RNA-seq was employed to study the changes of the proteins after castration in cattle. The results showed the differential expression proteins between castrated cattle and noncastrated cattle were mainly lied in immunity, lipid and fatty acid metabolism and protein synthesis. Through GO and KEGG pathway enrichment analysis, the differential expression proteins were enriched in PPAR pathway which involved in meat quality traits and lipid metabolism and immunity. In addition, the genes were mainly involved in metabolic pathways, such as ECM-receptor, interaction MAPK, signaling pathway PPAR, protein phosphorylation. The function of the proteins involved in castration were not clear and needed further researches. [ABSTRACT FROM AUTHOR]

Anti-obesity effect of chito-oligosaccharides (CO), resistant starch (RS) and their complexes (CO-RS) was investigated using high-fat fed rats. All of three intervention groups showed anti-obesity effect in the following order: CO-RS > CO > RS. This study revealed CO-RS administration achieved the lightest body weight, the lowest liver weight/index and the highest level of total antioxidant capacity in serum. The RNA sequencing data indicated that peroxisome proliferator-activated receptor (PPAR) pathway was significantly enriched by CO-RS administration. Among the genes involved in PPAR pathway, changes in the expression of Cyp7a1 gene were noticed, indicating an accelerated conversion of cholesterol into bile acids. Furthermore, the current study also revealed that, compared to the high-fat diet control, intervention with CO-RS led to significant reduction in mRNA expression of insulin-induced genes ( Insig-1 ), which did not occur in other two interventions, suggesting a different regulatory pathway affecting lipids metabolism compared with either CO or RS. [ABSTRACT FROM AUTHOR]

Diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) are the two most widely used plasticizers (PAEs) that may act as endocrine disruptors and cause developmental toxicity. We measured intrauterine exposure to DEHP and DBP which are the two most widely used phthalates (PAEs) in the cord blood of 50 postpartum women using ultra-HPLC-tandem mass spectrometry and solid-phase extraction. The embryotoxicity of DEHP and DBP was evaluated using the human embryonic stem cell test (hEST). Based on the intrauterine exposure concentration of DEHP and DBP in pregnant women and the reference point of toxic effects in hEST, we used the reference point index (RPI) method to assess the cumulative risk of DBP and DEHP. The mean concentrations of DEHP and DBP were 99.9 μg/L and 24.7 μg/L, respectively. DEHP and DBP were weakly embryotoxic, and the benchmark dose lower confidence intervals were 29.99 and 0.99 μg/mL, respectively, as determined using hEST. Both DEHP and DBP inhibited embryonic development via PPAR/PTEN/Akt signal pathway. The findings suggest that the cumulative risk in pregnant women with a high level of exposure should receive more attention in the future. • DEHP and DBP intrauterine co-exposure was very common in Chinese pregnant women. • DEHP and DPB were evaluated as weak embryotoxic chemicals by hEST. • DBP triggered PPARγ and induced apoptosis via PTEN/Akt pathway. • The cumulative risk assessment suggested more attention should be paid in pregnant women. [ABSTRACT FROM AUTHOR]