Regulation of metabolism by circadian rhythms: Support from time-restricted eating, intestinal microbiota & omics analysis.

Circadian oscillatory system plays a key role in coordinating the metabolism of most organisms. Perturbation of genetic effects and misalignment of circadian rhythms result in circadian dysfunction and signs of metabolic disorders. The eating-fasting cycle can act on the peripheral circadian clocks, bypassing the photoperiod. Therefore, time-restricted eating (TRE) can improve metabolic health by adjusting eating rhythms, a process achieved through reprogramming of circadian genomes and metabolic programs at different tissue levels or remodeling of the intestinal microbiota, with omics technology allowing visualization of the regulatory processes. Here, we review recent advances in circadian regulation of metabolism, focus on the potential application of TRE for rescuing circadian dysfunction and metabolic disorders with the contribution of intestinal microbiota in between, and summarize the significance of omics technology.

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation.

Gut microbes play a crucial role in transforming primary bile acids (BAs) into secondary forms, which influence systemic metabolic processes. The rumen, a distinctive and critical microbial habitat in ruminants, boasts a diverse array of microbial species with multifaceted metabolic capabilities. There remains a gap in our understanding of BA metabolism within this ecosystem. Herein, through the analysis of 9371 metagenome-assembled genomes and 329 cultured organisms from the rumen, we identified two enzymes integral to BA metabolism: 3-dehydro-bile acid delta4,6-reductase (baiN) and the bile acid:Na + symporter family (BASS). Both in vitro and in vivo experiments were employed by introducing exogenous BAs. We revealed a transformation of BAs in rumen and found an enzyme cluster, including L-ribulose-5-phosphate 3-epimerase and dihydroorotate dehydrogenase. This cluster, distinct from the previously known BA-inducible operon responsible for 7α-dehydroxylation, suggests a previously unrecognized pathway potentially converting primary BAs into secondary BAs. Moreover, our in vivo experiments indicated that microbial BA administration in the rumen can modulate amino acid and lipid metabolism, with systemic impacts underscored by core secondary BAs and their metabolites. Our study provides insights into the rumen microbiome's role in BA metabolism, revealing a complex microbial pathway for BA biotransformation and its subsequent effect on host metabolic pathways, including those for glucose, amino acids, and lipids. This research not only advances our understanding of microbial BA metabolism but also underscores its wider implications for metabolic regulation, offering opportunities for improving animal and potentially human health.

Fat deposition and partitioning for meat production in cattle and sheep.

In markets for beef and sheep meat, an appropriate level of intramuscular fat (IMF) is highly desirable for meat-eating quality, but strategies to improve it usually lead to an undesirable excess in carcase fat, presenting a major challenge to livestock producers. To solve this problem, we need to understand the partitioning of fat among the major fat depots: IMF, subcutaneous fat (SCF) and visceral fat (VF). In most genotypes of cattle and sheep, the rate of accretion is lower for IMF than for SCF and VF, so genetic selection for a high level of IMF, or the use of an increased dietary energy supply to promote IMF deposition, will increase overall fatness and feed costs. On the other hand, feeding postnatal calves with excessive concentrates promotes IMF deposition, so a nutritional strategy is feasible. With genetic strategies, several problems arise: 1) positive genetic correlations between IMF, SCF and VF differ among genotypes in both cattle and sheep; 2) genotypes appear to have specific, characteristic rates of accretion of IMF during periods of growth and fattening; 3) most breeds of cattle and sheep naturally produce meat with relatively low levels of IMF, but IMF does vary substantially among individuals and breeds so progress is possible through accurate measurement of IMF. Therefore, an essential prerequisite for selection will be knowledge of the genetic correlations and fat accretion rates for each genotype. Currently, selection for IMF is based on existing technology that directly measures IMF in the progeny or siblings, or estimates IMF in live animals. New technology is needed to permit the simultaneous measurement of SCF and IMF in the field, thus opening up the possibility of accurate selection, particularly for fat partitioning in live animals. Specifically, there would be great value in detecting individuals with an IMF advantage at an early age so the generation interval could be shortened and genetic gain accelerated. Genetic gain would also be greatly aided if we could select for genes that control adipogenesis and lipogenesis and are also differentially expressed in the various depots.

Long-Term Benefits of Cenchrus fungigraminus Residual Roots Improved the Quality and Microbial Diversity of Rhizosphere Sandy Soil through Cellulose Degradation in the Ulan Buh Desert, Northwest China.

Long-term plant residue retention can effectively replenish soil quality and fertility. In this study, we collected rhizosphere soil from the residual roots of annual Cenchrus fungigraminus in the Ulan Buh Desert over the past 10 years. The area, depth, and length of these roots decreased over time. The cellulose content of the residual roots was significantly higher in the later 5 years (2018-2022) than the former 5 years (2013-2017), reaching its highest value in 2021. The lignin content of the residual roots did not differ across samples except in 2015 and reached its highest level in 2021. The total sugar of the residual roots in 2022 was 227.88 ± 30.69 mg·g-1, which was significantly higher than that in other years. Compared to the original sandy soil, the soil organic matter and soil microbial biomass carbon (SMBC) contents were 2.17-2.41 times and 31.52-35.58% higher in the later 3 years (2020-2022) and reached the highest values in 2020. The residual roots also significantly enhanced the soil carbon stocks from 2018-2022. Soil dehydrogenase, nitrogenase, and N-acetyl-ß-D-glucosidase (S-NAG) were significantly affected from 2019-2022. The rhizosphere soil community richness and diversity of the bacterial and fungal communities significantly decreased with the duration of the residual roots in the sandy soil, and there was a significant difference for 10 years. Streptomyces, Bacillus, and Sphigomonas were the representative bacteria in the residual root rhizosphere soil, while Agaricales and Panaeolus were the enriched fungal genera. The distance-based redundancy analysis and partial least square path model results showed that the duration of residual roots in the sandy soil, S-NAG, and SMBC were the primary environmental characteristics that shaped the microbial community. These insights provide new ideas on how to foster the exploration of the use of annual herbaceous plants for sandy soil improvement in the future.

Postnatal feeding with high-fat combined with high-glucose diet induces precocious puberty in Sprague‒Dawley rat pups.

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.

Exploring the metabolomic landscape: Perilla frutescens as a promising enhancer of production, flavor, and nutrition in Tan lamb meat.

Addressing health-related concerns linked to the metabolite profile of lamb meat has become paramount, in line with the growing demand for enhanced flavor and taste. We examined the impact of Perilla frutescens seeds on Tan lamb growth, carcass traits, and metabolite profiles. Three diets were employed: a low-concentrate group (LC), a high-concentrate group (HC), and a PFS group (the LC diet supplemented with 3% Perilla frutescens seeds) on a dry matter basis. Forty-five male Tan-lambs (approximately six months) with similar body weights (25.1 kg ± 1.12 SD) were randomly assigned to one of these three groups for 84-day feeding, including an initial 14-day adjustment phase. The supplementation of PFS resulted in increased average daily gain (P < 0.01) and improved carcass quality and meat color (P < 0.05). Additionally, it led to an enhancement in omega-3 polyunsaturated fatty acids (P < 0.05) and a reduction in the omega-6/omega-3 ratio (P < 0.05). Using gas chromatography-mass spectrometry, 369 volatile compounds were identified with enhanced levels of acetaldehyde and 1,2,4-trimethyl-benzene associated with PFS (P < 0.05). Among the 807 compounds identified by ultra-high performance liquid chromatography-mass spectrometry, there were 66 significantly differential compounds (P < 0.05), including 43 hydrophilic metabolites and 23 lipids. PFS supplementation led to significant alterations in 66 metabolites, with three metabolites including 2,5-diisopropyl-3-methylphenol, 3-hydroxydecanoic acid, and lysophosphatidylcholine (15:0) emerging as potential PFS-related biomarkers. The study indicates that PFS supplementation can enhance Tan-lamb growth, feed efficiency, and meat quality, potentially providing lamb meat with improved flavor and nutritional characteristics.

SP2-induced circPUM1 modulates chemoresistance and nature killer cell toxicity in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

Hyocholic acid retards renal fibrosis by regulating lipid metabolism and inflammatory response in a sheep model.

The kidneys are vital organs that regulate metabolic homeostasis in the body, filter waste products from the blood, and remove extrahepatic bile acids. We previously found that the dietary supplementation of hyocholic acid alleviated the sheep body lipid deposition and decreased kidney weight. This study evaluated hyocholic acid's (HCA) roles and mechanisms on lipid metabolism and anti-inflammatory function in the kidney under a high-energy diet. Histomicrograph showing the apparent improvement by HCA by attenuating structural damage. The HCA treatment reduced the renal accumulation of cholesterol. Bile acid receptors such as LXR and FXR were activated at the protein level. HCA significantly altered several genes related to immune response (NF-κB, IL-6, and MCP1) and fibrosis (TGF-ß, Col1α1, and α-SMA). These significant changes correlated with renal lipid accumulation. The KEGG pathways including non-alcoholic fatty liver disease, insulin resistance, TNF signaling pathway, and Th17 cell differentiation were enriched and NF-κB, IL-6, and TGF-ß were identified as the core interconnected genes. This study revealed that HCA plays an efficient role in alleviating kidney lipids accumulation and inflammatory response through crucial genes such as FXR, LXR, HMGCR, NF-κB, IL-6, MCP1, and TGF-ß, and expand our understanding of HCA's role in kidney function. In conclusion, HCA mitigated kidney fibrosis, lipid metabolism disorders and immune responses induced by a high-energy diet by regulating a potential LXR/SREBP2/TGF-ß-NF-κB signaling pathway.

Gut microbiome combined with metabolomics reveals biomarkers and pathways in central precocious puberty.

BACKGROUND: Central precocious puberty (CPP) is a common disease in prepubertal children and results mainly from disorders in the endocrine system. Emerging evidence has highlighted the involvement of gut microbes in hormone secretion, but their roles and downstream metabolic pathways in CPP remain unknown. METHODS: To explore the gut microbes and metabolism alterations in CPP, we performed the 16S rRNA sequencing and untargeted metabolomics profiling for 91 CPP patients and 59 healthy controls. Bioinformatics and statistical analyses, including the comparisons of alpha and beta diversity, abundances of microbes, were undertaken on the 16S rRNA gene sequences and metabolism profiling. Classifiers were constructed based on the microorganisms and metabolites. Functional and pathway enrichment analyses were performed for identification of the altered microorganisms and metabolites in CPP. RESULTS: We integrated a multi-omics approach to investigate the alterations and functional characteristics of gut microbes and metabolites in CPP patients. The fecal microbiome profiles and fecal and blood metabolite profiles for 91 CPP patients and 59 healthy controls were generated and compared. We identified the altered microorganisms and metabolites during the development of CPP and constructed a machine learning-based classifier for distinguishing CPP. The Area Under Curves (AUCs) of the classifies were ranged from 0.832 to 1.00. In addition, functional analysis of the gut microbiota revealed that the nitric oxide synthesis was closely associated with the progression of CPP. Finally, we investigated the metabolic potential of gut microbes and discovered the genus Streptococcus could be a candidate molecular marker for CPP treatment. CONCLUSIONS: Overall, we utilized multi-omics data from microorganisms and metabolites to build a classifier for discriminating CPP patients from the common populations and recognized potential therapeutic molecular markers for CPP through comprehensive analyses.

Rumen microbial-driven metabolite from grazing lambs potentially regulates body fatty acid metabolism by lipid-related genes in liver.

BACKGROUND: Lipid metabolism differs significantly between grazing and stall-feeding lambs, affecting the quality of livestock products. As two critical organs of lipid metabolism, the differences between feeding patterns on rumen and liver metabolism remain unclear. In this study, 16S rRNA, metagenomics, transcriptomics, and untargeted metabolomics were utilized to investigate the key rumen microorganisms and metabolites, as well as liver genes and metabolites associated with fatty acid metabolism under indoor feeding (F) and grazing (G). RESULTS: Compared with grazing, indoor feeding increased ruminal propionate content. Using metagenome sequencing in combination with 16S rRNA amplicon sequencing, the results showed that the abundance of propionate-producing Succiniclasticum and hydrogenating bacteria Tenericutes was enriched in the F group. For rumen metabolism, grazing caused up-regulation of EPA, DHA and oleic acid and down-regulation of decanoic acid, as well as, screening for 2-ketobutyric acid as a vital differential metabolite, which was enriched in the propionate metabolism pathway. In the liver, indoor feeding increased 3-hydroxypropanoate and citric acid content, causing changes in propionate metabolism and citrate cycle, while decreasing the ETA content. Then, the liver transcriptome revealed that 11 lipid-related genes were differentially expressed in the two feeding patterns. Correlation analysis showed that the expression of CYP4A6, FADS1, FADS2, ALDH6A1 and CYP2C23 was significantly associated with the propionate metabolism process, suggesting that propionate metabolism may be an important factor mediating the hepatic lipid metabolism. Besides, the unsaturated fatty acids in muscle, rumen and liver also had a close correlation. CONCLUSIONS: Overall, our data demonstrated that rumen microbial-driven metabolite from grazing lambs potentially regulates multiple hepatic lipid-related genes, ultimately affecting body fatty acid metabolism.

Encapsulation in Amylose Inclusion Complex Enhances the Stability and Release of Vitamin D.

Vitamin D plays a significant role in the physiological functions of the human body. However, the application of vitamin D in functional foods is limited due to its sensitivity to light and oxygen. Therefore, in this study, we developed an effective method to protect vitamin D by encapsulating it in amylose. In detail, vitamin D was encapsulated by amylose inclusion complex, followed by structural characterization and evaluation of its stability and release properties. The results of X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy showed that vitamin D was successfully encapsulated in the amylose inclusion complex, and the loading capacity was 1.96% ± 0.02%. The photostability and thermal stability of vitamin D after encapsulation was increased by 59% and 28%, respectively. In addition, in vitro simulated digestion showed that vitamin D was protected through the simulated gastric environment and can be released gradually in the simulated intestinal fluid, implying its improved bioaccessibility. Our findings provide a practical strategy for the development of functional foods based on vitamin D.

Chinese Consumer Assessment of Australian Sheep Meat Using a Traditional Hotpot Cooking Method.

Hotpot is a widely popular cooking method for sheepmeat in China. This study measured the sensory responses of 720 untrained Chinese consumers to Australian sheepmeat cooked using a hotpot technique with methods based on Meat Standards Australia protocols. Shoulder and leg cuts of 108 lambs and 109 yearlings were scored on tenderness, juiciness, flavour and overall liking with linear mixed effects models used to analyse the influence of muscle type and animal factors on these scores. On average, shoulder cuts were more palatable than legs cuts for all sensory traits (p < 0.01) and lambs compared to yearlings (p < 0.05). Intramuscular fat and muscularity were identified as strong drivers of eating quality (p < 0.05), with greater palatability for both cuts as intramuscular fat increased (range 2.5 to 7.5%), and muscularity decreased (as measured through loin weight adjusted for hot carcase weight). Consumers were unable to detect differences between animal sire type and sex in sheepmeat hotpot. These findings suggest shoulder and leg cuts performed comparatively well in hotpot compared to previously tested sheepmeat cooking methods and emphasise the importance of balanced selection for quality and yield traits to ensure that consumer satisfaction is maintained.

Fermentation Quality, In Vitro Digestibility, and Aerobic Stability of Ensiling Spent Mushroom Substrate with Microbial Additives.

This experiment investigated the effects of lactic acid bacteria and cellulase on the fermentation quality, in vitro digestibility, and aerobic stability of Flammulina velutipes spent mushroom substrate silage (F-silage) and Pleurotus eryngii spent mushroom substrate silage (P-silage). Silage treatments included groups without any additives (control), with lactic acid bacteria (L), with cellulase (E), and with lactic acid bacteria and cellulase (M). Data analysis was performed using independent sample t-test and analysis of variance. After 45 days of ensiling, the pH in F-silage and P-silage from the L, E, and M groups were lower than those in the control group (p < 0.05). The pH, acetic acid (AA), and propionic acid (PA) levels in P-silage were lower than those in F-silage, and the LA content in P-silage was higher than that in F-silage (p < 0.05). Compared with the control, the E treatment increased in vitro neutral detergent fibre digestibility (IVNDFD) and in vitro acid detergent fibre digestibility (IVADFD) in F-silage and P-silage (p < 0.05). The aerobic stability of F-silage inoculated with L increased (p < 0.05) by 24 h compared to the control. The aerobic stability of P-silage inoculated with M increased (p < 0.05) by 6 h compared to the control. The improvement in fermentation quality and aerobic stability is extremely large in terms of applying M in F-silage and P-silage. The E is effective in improving the in vitro digestibility of P-silage. The research results provide a theoretical basis for the production of high-quality spent mushroom substrate fermented feed.

Multi-omics reveals diet-induced metabolic disorders and liver inflammation via microbiota-gut-liver axis.

The gut microbiota medicated gut-liver axis is vital for liver function and health. We aimed to explore the underlying molecular mechanism of diet-induced metabolic liver disorders via microbiota-gut-liver axis using multi-omics. Metataxonomics, metaproteomics, transcriptomics, and metabolomics were conducted on liver tissue and biofluids (gastrointestinal contents and blood) to elucidate the microbial mechanism related to metabolic disorders and liver injury. The hepatic inflammation occurred based on histomorphology after feeding a long-term grain-based high-energy diet, and the serum biochemical parameters and proinflammatory cytokines were significantly activated. Metaproteomics analysis indicated that the high-energy diet reduced anti-infection, immunity, anti-oxidant functions, and increased cell death and damage of rumen microbiome. Ruminal Ruminococcus_2, Solobacterium, and Syntrophococcu and jejunal Pirellula were potential microbial markers of liver disorders. The high-energy diet promoted hepatic inflammatory response and cytokine/chemokine-mediated signaling pathways located in the core of the functional genomic network. The high-energy diet increased indoxyl sulfate and p-cresol sulfate and decreased triterpenoids in the liver that were the potential biomarkers associated with metabolic liver disorders. Integrated multi-omics analyses showed interactions among the rumen and jejunum microbiota, circulating metabolites, and liver gene expression, suggesting a systemic immune response and liver disorder that signals through the microbiota-gut-liver axis.

Transcriptome and targeted metabolome analysis provide insights into bile acids' new roles and mechanisms on fat deposition and meat quality in lamb.

Higher quality lamb carcasses with more muscle and less fat are crucial for consumer preference and healthy eating. This study evaluated bile acids' functional roles and mechanisms on fat deposition in lambs. Forty-five lambs were arranged into three groups with control (CON) and two types of bile acid treatments (BA1, mainly hyocholic acid; BA2, mainly hyodeoxycholic acid, ruminally protected). The BA1 treatment did not affect the dry matter intake, body weight, and the average daily gain but significantly decreased the body fat (assessed as GR value) compared to the CON (7.92 vs 5.55 mm). The BA2 decreased tail fat weight compared to CON (1.99 vs 1.51 kg). Both BA1 and BA2 significantly decreased the tail fat ratio (110 vs 89.8 vs 78.6 g/kg of carcass weight). No significant differences were found between the three groups' blood antioxidant capacity and immune characteristics. The RNA-sequencing analysis identified 46 differentially expressed genes between CON and BA2. Several pathways, including ferroptosis and fatty acid biosynthesis and core genes such as HSPA8, HIFIA, HEXB, ACSL6, and MAP1LC3B were changed mainly or significantly correlated with the tail fat weight or proportion phenotypes, can be selected as targeted gene markers related to regulating the tail fat. This study provided new insight into bile acids' roles and revealed their comprehensive mechanism in regulating fat distribution in ruminants and will facilitate improvements of lamb meat production with decreased subcutaneous and tail fat deposition.

Co-Clustering on Bipartite Graphs for Robust Model Fitting.

Recently, graph-based methods have been widely applied to model fitting. However, in these methods, association information is invariably lost when data points and model hypotheses are mapped to the graph domain. In this paper, we propose a novel model fitting method based on co-clustering on bipartite graphs (CBG) to estimate multiple model instances in data contaminated with outliers and noise. Model fitting is reformulated as a bipartite graph partition behavior. Specifically, we use a bipartite graph reduction technique to eliminate some insignificant vertices (outliers and invalid model hypotheses), thereby improving the reliability of the constructed bipartite graph and reducing the computational complexity. We then use a co-clustering algorithm to learn a structured optimal bipartite graph with exact connected components for partitioning that can directly estimate the model instances (i.e., post-processing steps are not required). The proposed method fully utilizes the duality of data points and model hypotheses on bipartite graphs, leading to superior fitting performance. Exhaustive experiments show that the proposed CBG method performs favorably when compared with several state-of-the-art fitting methods.

Integrative network analysis revealed the molecular function of folic acid on immunological enhancement in a sheep model.

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL, and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.

Circular GOLPH3 RNA exerts oncogenic effects in vitro by regulating the miRNA-1299/LIF axis in oral squamous cell carcinoma.

Circular RNAs, which are a novel subclass of noncoding RNAs, are reported to be involved in various biological processes. Aberrant expression of circular RNAs may promote cancer progression. The function of circular GOLPH3 RNA (circGOLPH3) in oral squamous cell carcinoma (OSCC) is unclear. In this study, the circGOLPH3 levels in OSCC cell lines were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function experiments were performed to evaluate the roles of circGOLPH3 in OSCC. Cell counting kit 8, migration, and invasion assays were performed to determine the functions of circGOLPH3. The mechanism of circGOLPH3 in OSCC was investigated using qRT-PCR, western blotting, luciferase activity, and RNA pull-down analyses. Furthermore, the function of circGOLPH3 in vivo was evaluated. circGOLPH3 derived from GOLPH3 was mainly localized to the cytoplasm and exhibited high stability. The expression of circGOLPH3 was upregulated in OSCC cells. circGOLPH3 promoted the growth of OSCC in vitro and in vivo. Additionally, circGOLPH3 upregulated OSCC cell migration and invasion. Mechanistically, circGOLPH3 functioned as a microRNA sponge and downregulated miR-1299 expression. miR-1299 downregulated the expression of LIF by targeting its 3'-untranslated region. Inhibition of the circGOLPH3/miR-1299/LIF axis suppressed the growth, migration, and invasion of OSCC cells. These findings indicate that the circGOLPH3/miR-1299/LIF axis promotes OSCC cell growth, migration, and invasion and that this axis is a potential therapeutic target for OSCC.

Assessment of components related to flavor and taste in Tan-lamb meat under different silage-feeding regimens using integrative metabolomics.

Two untargeted metabolomics approaches based on gas chromatography mass spectrometry and ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry were used to identify the effects of different feeding regimes (concentrate, corn silage, alfalfa silage, mulberry leaf silage) on the potential meat flavor and taste components of Tan-lamb. Among 31 identified volatiles, hexanal was affected by the alfalfa silage diet, and 3-hydroxydodecanoic acid was changed by the mulberry leaf silage diet. l-Pipecolic acid (area under the curve = 1, fold change = 0.18-0.48) and trimethylamine N-oxide (area under the curve = 1, fold change = 5.26-22.84) was the potential best discriminant biomarker under alfalfa silage and concentrate feeding, respectively. The hydrophilic components were more readily changed by feeding regimes than volatile flavor compounds. Our findings are helpful for the illustration of Tan-lamb meat chemistry and producing high-quality lamb meat with improved flavor and taste by corn silage, alfalfa silage, or mulberry leaf silage.

Vitamin E promotes ovine Sertoli cell proliferation by regulation of genes associated with cell division and the cell cycle.

The effect of Vitamin E on the proliferation of ovine Sertoli cells was investigated. Sertoli cells were isolated and treated with various amounts of Vitamin E (0 µM, 400 µM, 800 µM, 1000 µM, 1200 µM, 1400 µM and 1600 µM) for 24 h. We found that at the concentration of 1200 µM, Vitamin E promoted Sertoli cell proliferation very effectively. It also increased the proportion of cells in the G1 phase while reduced that in the S and G2/M phases, suggesting that its effect on Sertoli cell proliferation is achieved by enhancing progression through the cell cycle. In addition, Vitamin E significantly up-regulated the transcript level of the PDPN, BMP6, AMPKα, GSK3ß, Myc, and CDK6 genes and down-regulated that of PPARγ, Cyclin B1 and CDK4 as determined by qRT-PCR. Western blot analysis revealed that the expression of BMP6 and PDPN was also upregulated at the protein level, in accordance with the results of the qRT-PCR. Taken together, Vitamin E promoted Sertoli cell proliferation by affecting the expression of genes that regulate cell division and the cell cycle; this indicates that it can have a positive effect on sheep reproductive performance.