Objective To investigate the effect of TRIM7, an E3 ubiquitin protein ligase, on lipid accumulation in foam cells derived from mouse bone marrow-derived macrophages (BMDMs) and its mechanism.Methods Western blot and qRT-PCR were used to detect the expression changes of TRIM7 in BMDMs stimulated by oxidized low-density lipoprotein. Construct TRIM7 knockout BMDMs and TRIM7 overexpression THP-1 cell lines, and analyze the effect of TRIM7 on lipid metabolism of BMDMs through qRT-PCR, oil red staining, and total cholesterol content detection. Western blot was used to detect the phosphorylation levels of MAPK signaling pathway proteins in BMDMs after TRIM7 knockout. Immunoprecipitation detection of the interaction between TRIM7 and the upstream kinase TAK1 in the MAPK pathway.Results TRIM7 interacted directly with TAK1, TRIM7 knockout could enhance the phosphorylation activity of MAPK signaling pathway protein, up regulate the expression of CD36 and MSR1 and inhibit the expression of ABCA1, increase cholesterol uptake and reduce lipid excretion, and ultimately promote the formation of foam cells.Conclusion TRIM7 negatively regulates lipid accumulation in foam cells by inhibiting MAPK signaling pathway and scavenger receptor expression by directly binding to TAK1, which provides a potential new target for the treatment of atherosclerosis.

BackgroundRenal carcinoma is a common, aggressive urinary tract malignancy with notable clinical challenges such as severe treatment toxicity and poor patient outcomes; 18β-glycyrrhetinic acid (18β-GA), an active component of Chinese herb Glycyrrhiza uralensis, has potent anti-tumor activity, while its role and molecular mechanisms in renal cancer remain elusive.AimThis research investigates the mechanism through which 18β-GA suppresses renal cancer cell proliferation.MethodsCombining whole transcriptome sequencing and network pharmacology, we identified 18β-GA-regulated key molecule miR-27a-5p and its core renal cancer targets; Cell assays confirmed 18β-GA-mediated suppression of renal cancer cell proliferation. Lentivirus-mediated miR-27a-5p modulation verified its role in renal cancer proliferation, and Western blot detection of autophagy marker LC3 expression clarified the miR-27a-5p/LC3 axis involvement in the anti-renal cancer effects of 18β-GA.ResultsResearch shows 18β-GA may exert anti-renal cancer effects by targeting HMOX1, HCK, CASP1 and IDO1, with its mechanism linked to the autophagy pathway via functional enrichment analysis; whole transcriptome sequencing identified miR-27a-5p as the most significantly altered by 18β-GA in renal cancer cells. Experimental verification confirmed that 18β-GA downregulates miR-27a-5p to elevate the autophagy marker LC3II/LC3I ratio, activate autophagy, reduce 786-O and ACHN cell viability, promote apoptosis, inhibit colony formation, and thus suppress renal cancer cell proliferation.Conclusion18β-GA induces autophagy and inhibits proliferation of renal cancer cells by down-regulating miR-27a-5p and relieving its inhibition on the LC3-mediated autophagy pathway, suggesting that the miR-27a-5p/LC3 axis may be a key target for 18β-GA in the treatment of renal cancer.

Tuberculosis results from Mycobacterium tuberculosis (Mtb) infection. Immune responses controlled by Toll-like receptor 4 (TLR4) are closely associated with the host response to pathogens, including Mtb. NLRP3 inflammasome-mediated pyroptosis forms a significant part of the inflammatory response during Mtb infection, and endoplasmic reticulum stress (ERS) is implicated in the activation of the NLRP3 inflammasome. Here, the function of TLR4 in macrophage pyroptosis induced by infection with the Bacillus Calmette-Guérin (BCG) mycobacterial strain was investigated. It was found that infection with BCG activated TLR4 signaling, induced ERS and subsequent NLRP3 inflammasome activation, leading to pyroptosis in mouse lung tissues. The TLR4 inhibitor TAK 242 inhibited the ERS onset, NLRP3 inflammasome stimulation, and pyroptosis, while the ERS inhibitor TUDCA blocked both inflammasome activation and pyroptosis, and the NLRP3 inhibitor MCC950 specifically inhibited pyroptosis. Furthermore, TAK 242, TUDCA, and MCC950 all exacerbated lung injury caused by BCG infection and promoted BCG survival. Similarly, after in BCG-infected THP-1 macrophages, TLR4 signaling was found to mediate NLRP3 inflammasome activation through ERS, thereby inducing pyroptosis. In summary, BCG infection leads to macrophage pyroptosis via the TLR4/ERS/NLRP3 inflammasome signaling axis, providing new insights for further research into the pathogenesis and treatment of tuberculosis.

In the original publication [...].

OBJECTIVE:The aim of this study was to screen the biomarkers of ginger against gastric cancer (GC) by network pharmacology, WGCNA and machine algorithms. To find the upstream transcription factors and downstream signaling proteins constituting the signaling axis, so as to predict the possible mechanism of action of ginger against GC. METHODS:Ginger was screened for active ingredients and targets through public databases. GC genes were screened using disease database, GEO database and WGCNA. The intersection of the four was taken to obtain the potential core genes. Machine algorithms was used to screen the core genes. Clinical relevance analysis, gene mutation relationship, epigenetic regulation analysis, immune infiltration analysis and molecular docking validation were performed on the core genes. Find its upstream transcription factors and downstream signaling proteins through database. RESULTS:35 intersecting genes were obtained by databases and WGCNA analysis. Machine algorithms and PPI were combined to finally screen the core gene PRMT1. The upstream transcription factor of PRMT1 was identified as EGR1 and the downstream protein as BTG2 by database and molecular docking. CONCLUSION:In this study, we found that PRMT1 could be used as a biomarker for ginger against GC using network pharmacology, WGCNA and machine algorithms. We hypothesized that ginger may exert antitumor effects through PRMT1/BTG2, providing new insights into the pharmacological mechanism of ginger against GC.

BACKGROUND:Non-alcoholic steatohepatitis (NASH) progression is strongly associated with deteriorating hepatic function, primarily driven by free cholesterol (FC) accumulation-induced lipotoxicity. Emerging evidence highlights the regulatory role of mammalian Ste20-like kinase 1 (MST1) in modulating intrahepatic lipid homeostasis, suggesting its therapeutic potential for non-alcoholic fatty liver disease (NAFLD) management. This investigation seeks to elucidate the pathophysiological mechanisms through which MST1 modulates NASH progression. METHODS:The experimental design employed two murine genetic models-wild-type (WT) controls and MST1-knockout (MST1-KO) specimens-subjected to a nutritionally modified Western diet (WD) enriched with saturated fats, simple carbohydrates, and dietary cholesterol to induce non-alcoholic steatohepatitis (NASH) pathogenesis. Lentiviral transduction techniques facilitated targeted MST1 overexpression in WT animals maintained on this dietary regimen. Parallel in vitro investigations utilized HepG2 hepatocyte cultures exposed to free fatty acid (FFA) cocktails comprising palmitic and oleic acids, coupled with CRISPR-mediated MST1 suppression and complementary gain-of-function manipulations to delineate molecular mechanisms. RESULTS:NASH triggers hepatic sterol biosynthesis activation, resulting in pathological FC overload concurrent with MST1 transcriptional suppression. Genetic ablation of MST1 amplifies intrahepatic FC retention and potentiates histopathological inflammation, while MST1 reconstitution mitigates steatotic FC deposition and attenuates inflammatory cascades. Mechanistic profiling revealed MST1-mediated AMPKα phosphorylation at Thr172, which suppresses cholesterogenic enzyme expression via sterol regulatory element-binding transcription factor 2 (SREBP2) axis modulation. This phosphorylation cascade demonstrates dose-dependent inhibition of HMGCR activity, resolving FC-induced hepatotoxicity. Crucially, MST1 orchestrates AMPK/SREBP2 crosstalk to maintain sterol homeostasis, with knockout models exhibiting 67% elevated SREBP2 nuclear translocation compared to controls. CONCLUSIONS:The regulatory axis involving MST1-mediated AMPK phosphorylation emerges as a promising therapeutic modality for modulating hepatic sterol metabolism. It demonstrates significant potential in arresting the progression of inflammatory cascades and extracellular matrix remodeling characteristic of NASH pathogenesis. Mechanistic studies confirm that this phosphorylation cascade effectively suppresses de novo lipogenesis while enhancing cholesterol efflux capacity, thereby establishing a dual-target strategy against both metabolic dysfunction and fibrotic transformation in preclinical models.

BACKGROUND:Lotus plumule and its active components have demonstrated inhibitory effects on gastric cancer (GC). However, the molecular mechanism of lotus plumule against GC remains unclear and requires further investigation. AIM:To identify the key hub genes associated with the anti-GC effects of lotus plumule. METHODS:This study investigated the potential targets of traditional Chinese medicine for inhibiting GC using weighted gene co-expression network analysis and bioinformatics. Initially, the active components and targets of the lotus plumule and the differentially expressed genes associated with GC were identified. Subsequently, a protein-protein interaction network was constructed to elucidate the interactions between drug targets and disease-related genes, facilitating the identification of hub genes within the network. The clinical significance of these hub genes was evaluated, and their upstream transcription factors and downstream targets were identified. The binding ability of a hub gene with its downstream targets was verified using molecular docking technology. Finally, molecular docking was performed to evaluate the binding affinity between the active ingredients of lotus plumule and the hub gene. RESULTS:This study identified 26 genes closely associated with GC. Machine learning analysis and external validation narrowed the list to four genes: Aldo-keto reductase family 1 member B10, fructose-bisphosphatase 1, protein arginine methyltransferase 1, and carbonic anhydrase 9. These genes indicated a strong correlation with anti-GC activity. CONCLUSION:Lotus plumule exhibits anti-GC effects. This study identified four hub genes with potential as novel targets for diagnosing and treating GC, providing innovative perspectives for its clinical management.

Female infertility represents a significant reproductive health issue that critically affects global fertility rates. In this study, we utilized the most recent data from the Global Burden of Disease (GBD) study 2021. Initially, we assessed the global burden by the number of female infertility prevalence and disability-adjusted life years (DALYs), along with the age-standardized rate (ASR) per 100,000 individuals, stratified by age, sociodemographic index (SDI), nationality, and region. Furthermore, linear regression models were employed to examine the temporal trends of disease burden from 1990 to 2021. Cluster analysis facilitated the evaluation of disease burden change patterns across different GBD regions. Lastly, the autoregressive composite moving average model was applied to forecast future disease burdens. In 2021, the global prevalence of female infertility was estimated at 110,089,459, contributing to 6,210,145 DALYs, there was an observed increase of 84.44% in prevalence and 84.43% in DALYs since 1990. The highest burden occurred among individuals aged 35-39, with the most rapid increase observed in the 30-34 age group. The burden of female infertility displayed considerable variability across GBD regions and countries, with areas of high-medium SDI facing elevated risks. Projections indicate a continuing rise in the ASR of prevalence and DALYs for female infertility over the next 2 decades. The global burden of female infertility has intensified from 1990 to 2021, with notable disparities across different SDI regions and countries. Women aged 35-39 face the highest risk, and there is a trend toward earlier onset of infertility.

Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent chronic liver condition, primarily characterized by excessive accumulation of fat within the liver. A pivotal factor in the progression of NAFLD is cholesterol deposition, which significantly exacerbates liver cell damage through the induction of endoplasmic reticulum (ER) stress. At the heart of this process is sterol regulatory element-binding protein 2 (SREBP2), a crucial transcription factor in cholesterol synthesis. The expression levels of SREBP2 are closely associated with the severity of NAFLD, marking it as a potential therapeutic target. In mouse liver, FOXO3a, a member of the forkhead box protein family, inhibits the expression of SREBP2. This regulation is further influenced by its phosphorylation by mammalian STE20-related kinase 1 (MST1). Our research has uncovered a novel pathway in a NAFLD model where MST1-induced phosphorylation facilitates the nuclear translocation of FOXO3a, leading to a subsequent inhibition of SREBP2 expression. This critical modulation not only curtails cholesterol synthesis but also mitigates cholesterol deposition, alleviates ER stress, and repairs liver cell damage. These findings highlight the MST1-FOXO3a-SREBP2 axis as a promising new target for NAFLD treatment strategies, offering potential pathways to ameliorate a disease that affects millions worldwide.

Abnormal or excessive fat accumulation caused by a sedentary lifestyle and a high-fat diet (HFD) lead to a loss of muscle mass and strength, ultimately resulting in sarcopenia, a condition known as sarcopenic obesity This study aimed to investigate the effects of Lycium barbarum polysaccharide (LBP) on SO and to explore the underlying mechanisms in order to evaluate its potential as a natural therapeutic agent. Male C57BL/6J mice were fed an HFD weeks, with LBP administration beginning after 8 weeks and continuing for 9 weeks. Body weight was measured weekly. Following euthanasia, histological analysis of muscle fibers, blood lipid profiling, muscle triglyceride extraction, and western blot analysis were conducted. In vitro, confluent C2C12 myoblasts were differentiated over 4 days and subsequently co-treated with LBP and palmitic acid (PA) for 24 hours. Our results demonstrated that LBP administration significantly reduced body weight, mesenteric fat mass, and adipocyte cross-sectional area (CSA). Concurrently, LBP increased muscle weight and muscle fiber CSA while decreasing the expression of atrophy-related markers, including muscle atrophy protein (Atrogin-1) and muscle RING-finger protein 1 (MuRF1). Furthermore, LBP improved glucose tolerance and insulin sensitivity by modulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which mitigated excessive lipid accumulation and ectopic fat deposition in skeletal muscle. Activation of the PI3K/AKT pathway LBP enhanced muscle protein synthesis through increased phosphorylation of p70 ribosomal protein S6 kinase and inhibition of glycogen synthase kinase3 beta, while simultaneously suppressing muscle protein degradation by downregulating the expression of Atrogin-1, MuRF1, myostatin, activin A receptor type II B (ActRIIB), and Smad2/3. These findings suggest that LBP promising natural agent for the prevention and treatment of SO, exerting its protective effects by correcting glucolipid metabolic disorders and restoring the balance between protein synthesis and degradation in skeletal muscle via the reactivation impaired PI3K/AKT pathway.

This study aimed to investigate the role of FAM172A in epithelial ovarian cancer (EOC), a highly lethal gynecological malignancy often diagnosed at late stages with limited treatment options. FAM172A expression was evaluated in EOC and normal ovarian tissues using western blotting and immunohistochemistry, and its association with patient prognosis, treatment response, and CA125 levels was assessed by multivariate regression analysis. Functional assays were performed to examine the effects of FAM172A on EOC cell proliferation, migration, and invasion. In vivo models were used to evaluate the influence of FAM172A on tumor growth, metastasis, and chemosensitivity. The underlying mechanism was explored by modulating the PI3K-Akt pathway with pharmacological inhibitors and activators. FAM172A was significantly upregulated in EOC tissues, and its elevated expression correlated with poor prognosis, chemotherapy resistance, and increased CA125 levels. Multivariate analysis identified FAM172A expression, platinum sensitivity, and CA125 as independent prognostic factors. In vitro, FAM172A promoted malignant behavior and conferred resistance to cisplatin. In vivo, knockdown of FAM172A suppressed tumor progression and enhanced the efficacy of cisplatin. Mechanistically, FAM172A exerted its effects through regulation of the PI3K-Akt pathway, and modulation of PI3K signaling rescued FAM172A-induced phenotypic changes. These findings highlight FAM172A as a critical promoter of EOC progression, associated with aggressive tumor characteristics and treatment failure. By activating the PI3K-Akt pathway, FAM172A represents a promising therapeutic target for EOC, potentially offering new strategies to improve patient outcomes, particularly in overcoming chemoresistance.

Background Peroxisome proliferator-activated receptor α and-γ (PPARα/γ) are known to play crucial roles in acute liver injury (ALI). Icariside II (ICS II), a natural flavonoid compound derived from Herba EpimedII, confers neuroprotection with PPARα/γ induction potency. Purpose This study was aimed to explore whether ICS II has the capacity to protect against ALI, and the role of PPARα/γ in the beneficial effect of ICS II on ALI. Methods Mice challenged by D-galactosamine (GalN)/lipopolysaccharide (LPS) and Kupffer cells (KCs) upon LPS insult were used as ALI models in vivo and in vitro. PPARα/γ-deficient mice were treated with ICS II to validate the potential targets of ICS II on ALI. Results We found that ICS II (5, 10, 20 mg/kg) dose-dependently improved the survival rate and liver histology, decreased ALT and AST in GalN/LPS-treated mice. Furthermore, ICS II directly bound to PPARα/γ and increased their activities. The protective properties of ICS II were counteracted when PPARα/γ were knocked out in GalN/LPS-induced mice and LPS-induced KCs, respectively. Mechanistically, ICS II restored mitochondrial function, reduced oxidative stress and inflammation through activating PPARα/γ, which activated Sirt6 and inhibited NF-κB nuclear translocation. Conclusion Our findings not only highlight PPARα/γ-SIRT6 signaling as a vital therapeutic target to combat ALI, but also reveal ICS II may serve as a novel dual PPARα/γ agonist to safeguard ALI from the oxidation-inflammation vicious circle by mediating SIRT6/NF-κB.

Identifying the specific factors secreted during early pregnancy is an effective method for pregnancy detection in cattle, helping to reduce empty pregnancies in the industry. To systematically investigate metabolic variations between early pregnancy and the estrous cycle and their relationship with pregnancy progression, this study utilized four-dimensional data-independent acquisition (4D-DIA) proteomics and liquid chromatography–tandem mass spectrometry (LC-MS/MS) metabolomics to analyze serum samples collected from Chinese native yellow cattle at day 0 and day 21 post-mating, combining bioinformatics analysis with experimental validation. The platelet activation signaling pathway and angiogenesis-related proteins were significantly upregulated. Among them, fibrinogen alpha/beta/gamma chains (FG) exhibited notable differences, with their branched-chain protein FGB showing highly significant upregulation (p = 0.003, Log2FC = 2.167) and tending to increase gradually during early pregnancy, suggesting that FGB could be one of the important indicators of early pregnancy in Chinese native yellow cattle. Among the differential metabolites, 11-Deoxy prostaglandin F1α (p < 0.001, Log2FC = 1.563), Thromboxane B1 (p = 0.002, Log2FC = 3.335), and Homo-Gamma-Linolenic Acid (C20:3) (p = 0.018, Log2FC = 1.781) were also increased, indicating their involvement in the regulation of the platelet activation signaling pathway. The platelet activation signaling pathway plays a crucial role in maternal immune tolerance and placental vascularization, which are essential for embryo implantation and placental development. These findings indicate that FGB has the potential to be a valuable biomarker for early cattle pregnancy detection, thereby improving pregnancy diagnosis accuracy, reducing economic losses caused by undetected empty pregnancies and enhancing reproductive efficiency in the cattle industry. Undoubtedly, our research outcomes must be validated with future studies, and a larger sample size as well as the evaluation of the potential endocrine effects induced by the synchronized estrus treatment must be considered.

Sarcopenic obesity (SO) defined as the coexistence of obesity and sarcopenia. While the anti-obesity effects of Lycium barbarum polysaccharide (LBP), the main component of L. barbarum extract, are known, its efficacy against SO remains unexplored. Consequently, we aimed to investigate the therapeutic effects of LBP on SO and the elucidate the underlying mechanisms. Our results revealed that LBP administration decreased obesity-related factors, and increased muscle-related factors in mice fed a high-fat diet (HFD). LBP administration ameliorated PA- and HFD-induced hyperglycaemia by modulating IRS-1 and GLUT-4 levels while also mitigating the ectopic fat deposition. Furthermore, our results demonstrated that LBP can mitigate mitochondrial structural abnormalities and dysfunction—characterized by increased mitochondrial membrane potential and ATP levels, reduced reactive oxygen species levels—through the activation of mitophagy. However, these beneficial effects of LBP on skeletal muscle were negated by AMPK inhibitor and siRNA knockdown of Parkin expression. Taken together, our findings indicate that LBP may effectively modulate glucose and lipid metabolism while ameliorating skeletal muscle atrophy via the activation of the AMPK/PINK1/Parkin-mediated mitophagy pathway, thereby repairing the mitochondrial structure and function. Consequently, LBP emerges as a promising therapeutic candidate for addressing obesity-related impacts on skeletal muscle.

WDFY4 plays an essential role in the immune system by regulating B-cell growth and development and participating in antigen processing during cross-presentation. WDFY4 is closely related to asthma and systemic lupus erythematosus; however, its role in cancer remains unclear. The purpose of this study is to use bioinformatics to determine whether abnormal expression of WDFY4 is a risk factor for cancer and to preliminarily analyze the ways in which WDFY4 affects cancer through experiments. R language packages and bioinformatic database were used to mine the potential carcinogenic effect of WDFY4 and analyze the differential WDFY4 expression in cancer, gene mutations, different tumor prognoses, immune cell infiltration, tumor microenvironment, and DNA methylation correlation. H1975 and A549 cell lines were infected with lentiviruses to overexpress WDFY4, and the effect of WDFY4 on the activity, proliferation, apoptosis, and cell cycle of lung cancer cells was analyzed. WDFY4 was differentially expressed in human tumors in unpaired and paired samples. The differential expression of WDFY4 in unpaired and paired or protein samples from the Clinical Proteome Tumor Analysis Consortium of eight cancers was consistent. WDFY4 methylation was downregulated in 17 cancer types and caused prognostic differences in different directions in some cancers. WDFY4 overexpression significantly inhibited the activity and proliferation of lung cancer cell lines, promoted apoptosis, and caused cell cycle arrest. Differential WDFY4 expression in cancers leads to differences in the prognosis of various cancers. WDFY4 can be an independent prognostic factor for glioma, KIRC, and LUSC.

Low fertility is the main cause of the low productivity in beef cattle and is mainly associated with a lack of conception after fertilization. The establishment of early pregnancy in cattle is a complex physiological process, and embryo implantation is crucial for the successful establishment of pregnancy. Exosomal miRNAs play an important role in regulating mammalian embryo implantation and development. This study used synchronous estrus technology to extract exosomes from bovine serum at 0, 14, and 21 days of early pregnancy and analyzed the expression profile of exosomal miRNAs through RNA-seq technology. We identified 472 miRNA precursor sequences and 367 mature miRNA sequences in the three sample groups, with the majority of the miRNAs having high abundance. Differentially expressed miRNAs (DEmiRNAs) were screened, and 20 DEmiRNAs were obtained. The differential expression analysis results show that compared to day 0, there were 15 DEmiRNAs in the serum on day 14 and 5 on day 21 of pregnancy. Compared to the 14th day of pregnancy, there were eight DEmiRNAs in the serum on the 21st day of pregnancy. Bioinformatics analysis shows that the target genes of DEmiRNAs regulated the signaling pathways closely related to early pregnancy, including the VEGF, NF-κB, and MAPK signaling pathways. In addition, the newly discovered miRNAs were bta-miR-3604, bta-miR-2889, bta-miR-3432a, and bta-miR-409b. These results provide a theoretical reference for screening the molecular markers for early pregnancy establishment and maternal recognition of pregnancy (MRP) in cattle and new ideas for shortening the calving interval in cows.

Objective Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disease that entails dysregulated ovulation, hyperandrogenism, and polycystic ovaries. While Wnt5a has been suggested to play key roles in follicular development and female fertility under normal conditions, its functions in the context of PCOS have yet to be established. This study was thus designed to explore the impact of Wnt5a on ovarian granulosa cell autophagy in PCOS, providing in vitro evidence in support of its role in this setting. Methods DHT-induced granulosa (KGN) cells were used as an in vitro model, and Wnt5a and autophagy-related protein levels in these cells were detected via Western blotting. Downregulating the expression of Wnt5a in KGN cells (by interference and inhibitor) was also performed, and Western blotting, RT-PCR, and immunofluorescence strategies were used to detect autophagy-related and PI3K/AKT/mTOR pathway-associated factors in this setting. In vivo, BOX5 was tested as a therapeutic inhibitor of Wnt5a in a murine model of DHEA-induced PCOS. Changes in ovarian morphology were detected through hematoxylin staining, while E2 and T hormone levels were quantified by ELISA, and autophagy-related factors in these animals were quantified through Western blotting, immunofluorescence, and immunohistochemistry. Results Wnt5a and autophagy-related protein levels rose significantly in DHT-induced KGN cells. Following downregulation of the Wnt5a in these cells, a significant decrease in autophagy-related factor levels was noted relative to the DHT group, together with significant increases in pathway-related factors. In mice, BOX5 treatment was sufficient to restore serum levels of androgen and to improve polycystic ovarian changes, while also suppressing the levels of autophagy-associated factors within ovarian granulosa cells. Conclusion Wnt5a downregulation suppresses autophagy in PCOS granulosa cells through the activation of the PI3K/AKT/mTOR pathway, in addition to remediating polycystic ovarian changes and normalizing serum levels of sex hormones.

Atherosclerosis (AS) is a chronic inflammatory arterial disease, in which abnormal lipid metabolism and foam cell formation play key roles. Histamine is a vital biogenic amine catalyzed by histidine decarboxylase (HDC) from L-histidine. Histamine H1 receptor (H1R) antagonist is a commonly encountered anti-allergic agent in the clinic. However, the role and mechanism of H1R in atherosclerosis have not been fully elucidated. Here, we explored the effect of H1R on atherosclerosis using Apolipoprotein E-knockout (ApoE−/−) mice with astemizole (AST, a long-acting H1R antagonist) treatment. The results showed that AST increased atherosclerotic plaque area and hepatic lipid accumulation in mice. The result of microarray study identified a significant change of endothelial lipase (LIPG) in CD11b+ myeloid cells derived from HDC-knockout (HDC−/−) mice compared to WT mice. Blocking H1R promoted the formation of foam cells from bone marrow-derived macrophages (BMDMs) of mice by up-regulating p38 mitogen-activated protein kinase (p38 MAPK) and LIPG signaling pathway. Taken together, these findings demonstrate that blocking H1R signal aggravates atherosclerosis by promoting abnormal lipid metabolism and macrophage-derived foam cell formation via p38 MAPK-LIPG signaling pathway.

Lei Liu was not included as an author in the original publication [...]