Dihydroartemisinin inhibits HNSCC invasion and migration by controlling miR-195-5p expression.

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

Accumulation mechanism of metabolite markers identified by machine learning between Qingyuan and Xiushui counties in Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua is a traditional Chinese medicinal plant acclaimed for its therapeutic potential in diabetes and various chronic diseases. Its rhizomes are the main functional parts rich in secondary metabolites, such as flavonoids and saponins. But their quality varies by region, posing challenges for industrial and medicinal application of P. cyrtonema. In this study, 482 metabolites were identified in P. cyrtonema rhizome from Qingyuan and Xiushui counties. Cluster analysis showed that samples between these two regions had distinct secondary metabolite profiles. Machine learning methods, specifically support vector machine-recursive feature elimination and random forest, were utilized to further identify metabolite markers including flavonoids, phenolic acids, and lignans. Comparative transcriptomics and weighted gene co-expression analysis were performed to uncover potential candidate genes including CHI, UGT1, and PcOMT10/11/12/13 associated with these compounds. Functional assays using tobacco transient expression system revealed that PcOMT10/11/12/13 indeed impacted metabolic fluxes of the phenylpropanoid pathway and phenylpropanoid-related metabolites such as chrysoeriol-6,8-di-C-glucoside, syringaresinol-4'-O-glucopyranosid, and 1-O-Sinapoyl-D-glucose. These findings identified metabolite markers between these two regions and provided valuable genetic insights for engineering the biosynthesis of these compounds.

Co-expressed network analysis based on 289 transcriptome samples reveals methyl jasmonate-mediated gene regulatory mechanism of flavonoid compounds in Dendrobium catenatum.

Flavonoids are momentous bioactive ingredients in orchid plant Dendrobium catenatum (D. catenatum), which are bioactive compounds with great medical and commercial potential. However, the accurate dissection of flavonoids profiling and their accumulation mechanism are largely unknown. In this study, methyl jasmonate (MeJA) treatment was used to investigate the change of flavonoids content and transcripts in two D. catenatum clones (A6 and B1). We identified 40 flavonoids using liquid chromatograph mass spectrometer (LC-MS). By weighted gene co-expressed network analysis (WGCNA) of flavonoids content and transcript expression of MeJA-treated samples, 37 hub genes were identified. Among them, DcCHIL, DcFLS, and DcDFR were highly correlation with two key transcription factors DcWRKY3/4 by correlation analysis of large-scale transcriptome data and above hub genes expression. Furthermore, transient overexpression of DcWRKY3/4 in tobacco leaves significantly increased the content of flavonoids. This study identified flavonoid profiling and built a new approach to mine regulatory mechanism of flavonoids in D. catenatum. These valuable flavonoids and gene resources will be key for understanding and harnessing natural flavonoids products in pharmaceuticals and foods industry of D. catenatum.

Genetic characteristics of lung adenocarcinoma with ground-glass opacity component.

Background: Increasing evidence suggests that ground-glass opacity featured lung adenocarcinoma (GGO-LUAD) and pure solid-LUAD have significantly different tumor biological behaviors; the former is usually indolent. Genetic variations fundamentally contribute to this distinct tumor behaviors. This study aims to investigate and compare the gene mutations using next-generation sequencing (NGS) technology in these two subtypes of LUAD. Methods: The clinical data and gene testing results of 46 patients suffering from LUAD with a histologically invasive subtype ≤3 cm and operated in the Thoracic Surgery Department of Beijing Tsinghua Changgung Hospital from May 2019 to December 2022 were retrospectively analyzed; a case-control study was performed to compare the pathological and genetic differences between LUAD with a GGO component and pure solid-LUAD. Results: Notable differences existed in vascular invasion, tumor spread through air spaces (STAS) and high-risk histological subtypes (micropapillary or solid subtypes) between the two types of LUAD with similar histologically invasive size. No significant difference was found in the mutation frequency of EGFR and KRAS. However, gene mutations were more prevalent in the cell cycle and TP53 signaling pathway for solid-LUAD. A significant difference was found in the mutation frequency of the tumor suppressor genes TP53 and CDKN2A between the two types. Conclusions: The wild-type TP53 and CDKN2A genes could potentially be used as molecular indicators for indolent LUAD characterized by GGO-featured.

Plant fructans: Recent advances in metabolism, evolution aspects and applications for human health.

Fructans, fructose polymers, are one of the three major reserve carbohydrate in plants. The nutritional and therapeutic benefits of natural fructans in plants have attracted increasing interest by consumers and food industry. In the course of evolution, many plants have developed the ability of regulating plant fructans metabolism to produce fructans with different structures and chain lengths, which are strongly correlated with their survival in harsh environments. Exploring these evolution-related genes in fructans biosynthesis and de novo domestication of fructans-rich plants based on genome editing is a viable and promising approach to improve human dietary quality and reduce the risk of chronic disease. These advances will greatly facilitate breeding and production of tailor-made fructans as a healthy food ingredient from wild plants such as huangjing (Polygonatum cyrtonema). The purpose of this review is to broaden our knowledge on plant fructans biosynthesis, evolution and benefits to human health.

Functional analysis of WOX family genes in Dendrobium catenatum during growth and development.

The WUSCHEL-Related Homeobox (WOX) family is a group of transcription factors unique to plants that play an important role in regulating key developmental processes such as stem cell maintenance and organ morphogenesis. As a rare and valuable Chinese herb, Dendrobium catenatum has a unique epiphytic lifestyle and growth and developmental characteristics, and a functional investigation of its WOX family genes can help to further understand the conserved and specific development of D. catenatum. In this study, we analyzed the phylogeny, spatio-temporal expression pattern and heterologous expression function of D. catenatum WOX family genes (DcWOX). The results showed that members of the D. catenatum WOX gene family could be divided into three evolutionary branches with significantly different tissue expression profiles. In transgenic Arabidopsis, overexpression of DcWOX4 resulted in significant dwarfism, pinnately leaf margins, and delayed flowering for 2 weeks; overexpression of DcWOX9 resulted in plant dwarfing, serrated leaf margin, delayed flowering for 1 week, and even male and female sterility in strong phenotype plants; overexpression of DcWOX11 caused curl downward leaf. The abnormal morphogenesis of DcWOX4/9/11 overexpression Arabidopsis leaves are related to the down-regulation of TCP family genes, CUC family genes and the up-regulation of KNOX family genes; Postponement of flowering is related to down-regulation of early flowering genes such as FT, SOC1 and CO. Therefore, this study showed that D. catenatum WOX family genes have important functions in regulating plant morphogenesis, leaf development, flowering time and fertility, further expanding the understanding of the WOX gene family function, and providing clues for the conservation and specificity during orchid development and evolution.

Interactions between endophytic fungus Pestalotiopsis sp. DO14 and Dendrobium catenatum: Deciphering plant polysaccharide and flavonoid accumulation and underlying mechanisms by comparative transcriptome and metabolome analyses.

Dendrobium catenatum, which belongs to the Orchidaceae family, has been used as a traditional medicine and healthy food in China for over 2000 years, and is of enormous economic value. Polysaccharides and flavonoids are two major functional ingredients in D. catenatum stems that contribute to its health benefits. D. catenatum lives in close association with endophytic fungi, but the literature regarding the further relations between them, especially the fungal-induced accumulation of metabolites in the host plant, is sparse. Our previous study showed that Pestalotiopsis sp. DO14 isolated from D. catenatum improved the host plant growth and metabolite accumulation. This study was performed to investigate dynamic variations of the growth traits, key metabolites (polysaccharides and flavonoids), and expression of key genes of D. catenatum under conditions of the DO14 colonization. Colonization with DO14 promoted D. catenatum growth as indicated by increased leaf area, mid-stem thickness, and plant height. The content of polysaccharides, mannose, and sucrose increased even without DO14 entering the host cells or forming a mature symbiotic relationship concurrent with improved photosynthesis rate. Furthermore, DO14 induced upregulation of genes involved in sugar and flavonoid metabolism, especially phosphoenolpyruvate carboxykinase (PCKA), chalcone synthase (CHS) and UDP-glycose flavonoid glycosyltransferase (UFGT). These observations suggested that endophytic fungi induce the accumulation of polysaccharides and flavonoids by plants, increasing the efficiency of carbon assimilation and carbon turnover. The findings of this study provide insight into the mechanisms underlying Orchidaceae-endophyte interactions, and suggest potential novel applications of endophytic fungi in D. catenatum breeding to improved plant quality.

Machine learning uncovers accumulation mechanism of flavonoid compounds in Polygonatum cyrtonema Hua.

The compositions and yield of flavonoid compounds of Polygonatum cyrtonema Hua (PC) are important indices of the quality of medicinal materials. However, the flavonoids compositions and accumulation mechanism are still unclear in PC. Here, we identified 22 flavonoids using widely-targeted metabolome analysis in 15 genotypes of PC. Then weighted gene co-expression network analysis based on 45 transcriptome samples was performed to construct 12 co-expressed modules, in which blue module highly correlated with flavonoids was identified. Furthermore, 4 feature genes including PcCHS1, PcCHI, PcCHS2 and PcCHR5 were identified from 94 hub genes in blue module via machine learning methods support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), and their functions on metabolic flux of flavonoids pathway were confirmed by tobacco transient expression system. Our findings identified representative flavonoids and key enzymes in PC that provided new insight for elite breeding rich in flavonoids, and thus will be beneficial for rapid development of great potential economic and medicinal value of PC.

Effects of Dietary Vitamin E on Intramuscular Fat Deposition and Transcriptome Profile of the Pectoral Muscle of Broilers.

Vitamin E is an essential micronutrient for animals. The aim of this study was to determine the effect of vitamin E on intramuscular fat (IMF) deposition and the transcriptome profile of the pectoral muscle in broiler chickens. Arbor Acres chickens were divided into five treatment groups fed a basal diet supplemented with 0, 20, 50, 75, and 100 IU/kg dietary DL-α-tocopheryl acetate (vitamin E), respectively. Body weight, carcass performance, and IMF content were recorded. Transcriptome profiles of the pectoral muscles of 35-day-old chickens in the control and treatment groups (100 IU/kg of vitamin E) were obtained by RNA sequencing. The results showed that diets supplemented with 100 IU/kg of vitamin E significantly increased IMF deposition in chickens on day 35. In total, 159 differentially expressed genes (DEGs), including 57 up-regulated and 102 down-regulated genes, were identified in the treatment (100 IU/kg vitamin E) group compared to the control group. These DEGs were significantly enriched in 13 Gene Ontology terms involved in muscle development and lipid metabolism; three signaling pathways, including the mitogen-activated protein kinase and FoxO signaling pathways, which play key roles in muscular and lipid metabolism; 28 biofunctional categories associated with skeletal and muscular system development; 17 lipid metabolism functional categories; and three lipid metabolism and muscle development-related networks. The DEGs, pathways, functional categories, and networks identified in this study provide new insights into the regulatory roles of vitamin E on IMF deposition in broilers. Therefore, diets supplemented with 100 IU/kg of vitamin E will be more beneficial to broiler production.

Bioactive compounds from Polygonatum genus as anti-diabetic agents with future perspectives.

Diabetes mellitus (DM) is one of the most serious health problems worldwide. Species in the genus Polygonatum are traditional food and medicinal plants, which play an important role in controlling blood glucose. In this reveiw, we systematically summarized the traditional and modern applications of the genus Polygonatum in DM, focused on the material bases of polysaccharides, flavonoids and saponins. We highlighted their mechanisms of action in preventing obese diabetes, improving insulin resistance, promoting insulin secretion, regulating intestinal microecology, inhibiting advanced glycation end products (AGEs) accumulation, suppressing carbohydrate digestion and obsorption and modulating gluconeogenesis. Based on the safety and efficacy of this 'medicinal food' and its utility in the prevention and treatment of diabetes, we proposed a research and development program that includs diet design (supplementary food), medical nutrition therapy and new drugs, which could provide new pathways for the use of natural plants in prevention and treatment of DM.

Glucomannan in Dendrobium catenatum: Bioactivities, Biosynthesis and Perspective.

Dendrobium catenatum is a classical and precious dual-use plant for both medicine and food in China. It was first recorded in Shen Nong's Herbal Classic, and has the traditional functions of nourishing yin, antipyresis, tonifying the stomach, and promoting fluid production. The stem is its medicinal part and is rich in active polysaccharide glucomannan. As an excellent dietary fiber, glucomannan has been experimentally confirmed to be involved in anti-cancer, enhancing immunity, lowering blood sugar and blood lipids, etc. Here, the status quo of the D. catenatum industry, the structure, bioactivities, biosynthesis pathway and key genes of glucomannan are systematically described to provide a crucial foundation and theoretical basis for understanding the value of D. catenatum and the potential application of glucomannan in crop biofortification.

Genome-wide analysis of basic helix-loop-helix genes in Dendrobium catenatum and functional characterization of DcMYC2 in jasmonate-mediated immunity to Sclerotium delphinii.

Dendrobium catenatum, belonging to the Orchidaceae, is a precious Chinese herbal medicine. Sclerotium delphinii (P1) is a broad-spectrum fungal disease, which causes widespread loss in the near-wild cultivation of D. catenatum. Thus, resistance breeding of D. catenatum has become the key to solve this problem. The basic helix-loop-helix (bHLH) gene family is closely related to plant resistance to external stresses, but the related research in D. catenatum is not deep enough yet. Phylogenetic analysis showed that 108 DcbHLH genes could be divided into 23 subgroups. Promoter cis-acting elements revealed that DcbHLHs contain a large number of stress-related cis-acting elements. Transcriptome analysis of MeJA and P1 treatment manifested that exogenous MeJA can change the expression pattern of most bHLH genes, especially the IIIe subgroup, including inhibiting the expression of DcbHLH026 (MYC2a) and promoting the expression of DcbHLH027 (MYC2b). Subcellular localization indicated that they were located in the nucleus. Furthermore, exogenous MeJA treatment significantly delayed disease time and reduced lesion size after infection with P1. DcMYC2b-overexpression Arabidopsis lines showed significantly smaller lesions after being infected with P1 than the wild type, indicating that DcMYC2b functions as an important positive regulator in D. catenatum defense against P1. Our findings shed more insights into the critical role of the DcbHLH family in plants and the resistance breeding of D. catenatum.

Developmental Characteristics and Auxin Response of Epiphytic Root in Dendrobium catenatum.

Dendrobium catenatum, a traditional precious Chinese herbal medicine, belongs to epiphytic orchids. Its special life mode leads to the specialization of roots, but there is a lack of systematic research. The aerial root in D. catenatum displays diverse unique biological characteristics, and it initially originates from the opposite pole of the shoot meristem within the protocorm. The root development of D. catenatum is not only regulated by internal cues but also adjusts accordingly with the change in growth environments. D. catenatum root is highly tolerant to auxin, which may be closely related to its epiphytic life. Exogenous auxin treatment has dual effects on D. catenatum roots: relatively low concentration promotes root elongation, which is related to the induced expression of cell wall synthesis genes; excessive concentration inhibits the differentiation of velamen and exodermis and promotes the overproliferation of cortical cells, which is related to the significant upregulation of WOX11-WOX5 regeneration pathway genes and cell division regulatory genes. Overexpression of D. catenatum WOX12 (DcWOX12) in Arabidopsis inhibits cell and organ differentiation, but induces cell dedifferentiation and callus production. Therefore, DcWOX12 not only retains the characteristics of ancestors as stem cell regulators, but also obtains stronger cell fate transformation ability than homologous genes of other species. These findings suggest that the aerial root of D. catenatum evolves special structure and developmental characteristics to adapt to epiphytic life, providing insight into ideal root structure breeding of simulated natural cultivation in D. catenatum and a novel target gene for improving the efficiency of monocot plant transformation.

Action Mechanisms of Effectors in Plant-Pathogen Interaction.

Plant pathogens are one of the main factors hindering the breeding of cash crops. Pathogens, including oomycetes, fungus, and bacteria, secrete effectors as invasion weapons to successfully invade and propagate in host plants. Here, we review recent advances made in the field of plant-pathogen interaction models and the action mechanisms of phytopathogenic effectors. The review illustrates how effectors from different species use similar and distinct strategies to infect host plants. We classify the main action mechanisms of effectors in plant-pathogen interactions according to the infestation process: targeting physical barriers for disruption, creating conditions conducive to infestation, protecting or masking themselves, interfering with host cell physiological activity, and manipulating plant downstream immune responses. The investigation of the functioning of plant pathogen effectors contributes to improved understanding of the molecular mechanisms of plant-pathogen interactions. This understanding has important theoretical value and is of practical significance in plant pathology and disease resistance genetics and breeding.

Jasmonate Signaling Pathway Modulates Plant Defense, Growth, and Their Trade-Offs.

Lipid-derived jasmonates (JAs) play a crucial role in a variety of plant development and defense mechanisms. In recent years, significant progress has been made toward understanding the JA signaling pathway. In this review, we discuss JA biosynthesis, as well as its core signaling pathway, termination mechanisms, and the evolutionary origin of JA signaling. JA regulates not only plant regeneration, reproductive growth, and vegetative growth but also the responses of plants to stresses, including pathogen as well as virus infection, herbivore attack, and abiotic stresses. We also focus on the JA signaling pathway, considering its crosstalk with the gibberellin (GA), auxin, and phytochrome signaling pathways for mediation of the trade-offs between growth and defense. In summary, JA signals regulate multiple outputs of plant defense and growth and act to balance growth and defense in order to adapt to complex environments.

Out of the Himalaya-Hengduan Mountains: Phylogenomics, biogeography and diversification of Polygonatum Mill. (Asparagaceae) in the Northern Hemisphere.

Clarifying the process of formation of diversity hotspots and the biogeographic connection between regions is critical in understanding the impact of environmental changes on organismal evolution. Polygonatum (Asparagaceae) is distributed across the Northern Hemisphere. It displays an uneven distribution, with more than 50% of its species occurring in the Himalaya-Hengduan Mountains (HHM). Here, we generated a time-calibrated phylogeny of Polygonatum, based on whole-plastome data, to reconstruct the genus' biogeographical history and morphological/chromosomal evolution. Our phylogenetic analyses strongly support the monophyly of Polygonatum and its division into three sections (i.e., Verticillata, Sibirica, and Polygonatum). Polygonatum originated from the HHM region during the early-Miocene (c. 20.10 Ma), and began to radiate since the mid-Miocene, driven by the uplift of the Qinghai-Tibet Plateau (QTP), increasingly colder/arid climates following the mid-Miocene Climatic Optimum (MMCO), and intensification of the East Asian winter monsoon. Dispersal from the HHM region to other regions was facilitated by the intensification of East Asian summer monsoon in response to global climatic warming during the MMCO. Decreasing dysploidy accompanied by karyotype change and polyploidization in Polygonatum appears to be associated with its diversification and colonization of new ecological niches. Our results highlight the importance of regional tectonic activities and past climatic changes from the Neogene onwards to the spatial-temporal diversification and distribution patterns of plant lineages with a wide distribution in the Northern Hemisphere. They also contribute to the knowledge of the uneven species richness between East Asia and other regions.

High expression of HOXB7 is an unfavorable prognostic factor for solid malignancies: A meta-analysis.

BACKGROUND: HOXB7 is abnormally expressed in a variety of tumors, but its prognostic value remains unclear due to sample size limitation and outcome inconsistency in previous studies. This meta-analysis was performed to explore the effect of HOXB7 expression on prognoses and clinicopathological factors in range of the whole solid tumors. METHODS: PubMed, EMBASE, and Web of Science databases were searched to identify included studies. Hazard ratios (HR) with its 95% confidence interval (CI) and clinicopathological factors were extracted. Subgroup analyses were performed according to histopathological type, tumor occurrence systems, and HOXB7 detection methods. RESULTS: A total of 3430 solid tumors patients from 20 studies (21 cohorts) were included in the meta-analysis. The results showed that high HOXB7 expression was significantly associated with worse survival (overall survival: HR = 1.98, 95%CI: 1.74-2.26, P < .001 and disease-free survival: HR = 1.59, 95%CI: 1.21-2.09, P = .001), more advanced tumor-node-metastasis (TNM) stage (odds ratio [OR] = 2.14, 95%CI: 1.68-2.73, P < .001), positive lymph node metastasis (OR = 2.16, 95%CI: 1.74-2.70, P < .001), more distant metastasis (OR = 1.63, 95%CI: 1.01-2.63, P = .048), poorer differentiation (OR = 1.48, 95%CI: 1.14-1.91, P = .003), and higher Ki-67 expression (OR = 2.53, 95%CI: 1.68-3.84, P < .001). Subgroup analysis showed that survival of patients with HOXB7 high expression was worse in either squamous cell carcinomas or non-squamous cell carcinomas, digestive tumors or non-digestive tumors, and protein level or mRNA level. CONCLUSION: High HOXB7 expression might be a valuable biomarker of poor prognosis for solid tumors. HOXB7 promotes tumor proliferation and metastasis, and is associated with poorer differentiation, more advanced stage, even the chemotherapy resistance, suggesting that HOXB7 is a potential therapeutic target for solid tumors.

Colonization and Development of the Fecal Microflora of South China Tiger Cubs (Panthera tigris amoyensis) by Sequencing of the 16S rRNA Gene.

Postnatal colonization and development of the gut microbiota is linked to health and growth. A comprehensive understanding of the postnatal compositional changes and development of the microbial community is helpful to understand the gut health and improve the survival rate of South China tiger cubs (Panthera tigris amoyensis). Fecal samples from three tiger cubs were collected on the day of birth in 2018 (June 17-21 [G0], July 18 [G1], July 31 [G2], and August 7 [G3]). The 16S rRNA genes of the fecal microflora were sequenced. Results showed that 38 phyla, 58 classes, 134 orders, 272 families, and 636 genera of bacteria from 3,059 operational taxonomic units were identified from 12 fecal samples. The diversity and abundance of species of group G0 were significantly higher (p < 0.05 or 0.01) than those of groups G2 and G3. The predominant phylum was Proteobacteria in groups G0 and G1 (38.85% and 48%, respectively) and Firmicutes in groups G2 and G3 (71.42% and 75.29%, respectively). At the phylum level, the abundance of Deinococcus-Thermus was significantly decreased in groups G1, G2, and G3 as compared to group G0 (p < 0.05), while that of Firmicutes was significantly increased in groups G2 and G3 (p < 0.05). At the genus level, the abundance of Faecalibacterium, Ralstonia, and unidentified Rickettsiales was significantly decreased in groups G1, G2, and G3 as compared with group G0 (p < 0.05), while that of Pseudomonas was significantly decreased in groups G2 and G3 (p < 0.05). The composition and structure of fecal microbiota of South China tiger cubs changed after birth.

IL-35 subunit EBI3 alleviates bleomycin-induced pulmonary fibrosis via suppressing DNA enrichment of STAT3.

BACKGROUND: IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. METHODS: Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. RESULTS: IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. CONCLUSION: IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.

Resveratrol reverses the programmed high-susceptibility to non-alcoholic fatty liver disease by targeting the hepatic SIRT1-SREBP1c pathway in prenatal ethanol-exposed rat offspring.

An increased susceptibility to non-alcoholic fatty liver disease (NAFLD) in female rat offspring that experienced prenatal ethanol exposure (PEE) has been previously demonstrated. The present study further investigated the potential mechanism. Based on the results from both fetal and adult studies of offspring rats that experienced PEE (4 g/kg/day), the fetal weight, serum glucose and triglyceride levels decreased significantly and hepatocellular ultra-structure was altered. Fetal livers exhibited inhibited expression and activity of sirtuin 1 (SIRT1), enhanced expression of lipogenic genes: sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FASN), acetyl-coenzyme A carboxylase α (ACCα), stearyl-coenzyme A desaturase 1 (SCD1). In adult offspring fed with high-fat diet, the PEE offspring revealed obviously catch-up growth, increased food intake, elevated serum metabolic phenotypes, suppressed hepatic SIRT1-SREBP1c pathway, and formation of NAFLD. Resveratrol (the chemical activator of SIRT1) could remarkably reverse the serum metabolic phenotypes and alleviate the hepatocyte steatosis in relation to the PEE offspring through activating the hepatic SIRT1-SREBP1c pathway. Therefore, increased susceptibility to diet-induced NAFLD in PEE offspring appears to be mediated by intrauterine programming of hepatic lipogenesis via the SIRT1-SREBP1c pathway. This altered programming effect could partially be reversed by resveratrol intervention after birth in PEE offspring rats.