TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor-1α.

BACKGROUND: Cardiac hypertrophy is an initiating link to Heart failure (HF) which still seriously endangers human health. Transferrin receptor (TFRC), which promotes iron uptake through the transferrin cycle, is essential for cardiac function. However, whether TFRC is involved in the process of pathological cardiac hypertrophy is not clear. METHODS: Transverse aortic constriction (TAC) mouse model and mice primary cardiomyocytes treated with isoproterenol (ISO) or phenylephrine (PHE) were used to mimic cardiac hypertrophy in vivo and in vitro. Single cell RNA sequence data from heart tissues of TAC-model mice was obtained from the Gene Expression Omnibus (GEO) database, and was analyzed with R package Seurat. TFRC expression and macrophage infiltration in the heart tissue were tested by immunofluorescent staining. Macrophage polarization was detected by Flow Cytometry. TFRC expressions were detected by qRT-PCR, Western blot, and ELISA. RESULTS: TFRC expression is increased in the pathological cardiac hypertrophy of mice model and positively associated with macrophage infiltration. Furthermore, TFRC in cardiomyocytes recruits and activates macrophages by secreting C-C motif ligand 2 (Ccl2) in the mice heart tissue with TAC surgery or in the primary cardiomyocytes stimulated with ISO or PHE to induce myocardial hypertrophy in vitro. Moreover, we find that TFRC promotes Ccl2 expression in cardiomyocytes via regulating signal transducer and activator of transcription 3 (STAT3). In addition, we find that increased TFRC expression in the HF tissue is regulated by hypoxia-inducible factor-1α (HIF-1α). CONCLUSION: This in-depth study shows that TFRC in cardiomyocytes promotes HF development through inducing macrophage infiltration and activation via the STAT3-Ccl2 signaling, and TFRC expression in cardiomyocytes is regulated by HIF-1α during HF. This study first uncovers the role of TFRC in cardiomyocytes on macrophage infiltration and activation during HF.

Cell- and noncell-autonomous AUXIN RESPONSE FACTOR3 controls meristem proliferation and phyllotactic patterns.

In cell-cell communication, noncell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression in Arabidopsis (Arabidopsis thaliana) is mainly activated at the periphery of the SAM by auxin where ARF3 cell autonomously regulates the expression of meristem-organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2), and TARGETS UNDER ETTIN CONTROL3 (TEC3) to regulate the arrangement of organs in regular pattern, a phenomenon referred to as phyllotaxis. We also show that ARF3 is translocated into the organizing center where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity noncell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell-cell communication in dynamic SAM maintenance.

Curcumin improves adipocytes browning and mitochondrial function in 3T3-L1 cells and obese rodent model.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro. Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.

Genomic profiling and expression analysis of the diacylglycerol kinase gene family in heterologous hexaploid wheat.

The inositol phospholipid signaling system mediates plant growth, development, and responses to adverse conditions. Diacylglycerol kinase (DGK) is one of the key enzymes in the phosphoinositide-cycle (PI-cycle), which catalyzes the phosphorylation of diacylglycerol (DAG) to form phosphatidic acid (PA). To date, comprehensive genomic and functional analyses of DGKs have not been reported in wheat. In this study, 24 DGK gene family members from the wheat genome (TaDGKs) were identified and analyzed. Each putative protein was found to consist of a DGK catalytic domain and an accessory domain. The analyses of phylogenetic and gene structure analyses revealed that each TaDGK gene could be grouped into clusters I, II, or III. In each phylogenetic subgroup, the TaDGKs demonstrated high conservation of functional domains, for example, of gene structure and amino acid sequences. Four coding sequences were then cloned from Chinese Spring wheat. Expression analysis of these four genes revealed that each had a unique spatial and developmental expression pattern, indicating their functional diversification across wheat growth and development processes. Additionally, TaDGKs were also prominently up-regulated under salt and drought stresses, suggesting their possible roles in dealing with adverse environmental conditions. Further cis-regulatory elements analysis elucidated transcriptional regulation and potential biological functions. These results provide valuable information for understanding the putative functions of DGKs in wheat and support deeper functional analysis of this pivotal gene family. The 24 TaDGKs identified and analyzed in this study provide a strong foundation for further exploration of the biological function and regulatory mechanisms of TaDGKs in response to environmental stimuli.

Yin Yang-1 suppresses CD40 ligand-CD40 signaling-mediated anti-inflammatory cytokine interleukin-10 expression in pulmonary adventitial fibroblasts by promoting histone H3 tri-methylation at lysine 27 modification on interleukin-10 promoter.

During the pathogenesis of early pulmonary arterial hypertension (PAH), pulmonary arterial adventitial fibroblast act as an initiator and mediator of inflammatory processes that predispose vessel walls to excessive vasoconstriction and pathogenic vascular remodeling. Emerging studies report that Yin Yang-1 (YY-1) plays important roles in inflammatory response and vascular injury. Our recent study finds that activation of CD40 ligand (CD40L)-CD40 signaling promotes pro-inflammatory phenotype of pulmonary adventitial fibroblasts. However, whether YY-1 is involved in CD40L-CD40 signaling-triggered inflammatory response in pulmonary adventitial fibroblasts and its underlying mechanism is still unclear. Here, we show that soluble CD40L (sCD40L) stimulation promotes YY-1 protein expression and suppresses anti-inflammatory cytokine, interleukin 10 (IL-10) expression in pulmonary adventitial fibroblasts, while YY-1 knockdown prevents sCD40L-mediated reduction of IL-10 expression via enhancing IL-10 gene transactivation. Further, we find that sCD40L stimulation significantly increases histone H3 tri-methylation at lysine 27 (H3K27me3) modification on IL-10 promoter in pulmonary adventitial fibroblasts, and YY-1 knockdown prevents the effect of sCD40L on IL-10 promoter by reducing the interaction with enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, binding to IL-10 promoter. Moreover, we find that sCD40L stimulation promotes YY-1 protein, but not messenger RNA (mRNA) expression, via decreasing N6-methyladenosine methylation on YY-1 mRNA to suppress YTHDF2-medicated mRNA decay. Overall, this in-depth study shows that the activation of CD40L-CD40 signaling upregulates YY-1 protein expression in pulmonary adventitial fibroblasts, which results in increasing YY-1 and EZH2 binding to the IL-10 promoter region to enhance H3K27me3 modification, eventually leading to suppression of IL-10 transactivation. This study first uncovers the roles of YY-1 on CD40L-CD40 signaling-triggered inflammatory response in pulmonary adventitial fibroblasts.

Relationship between fluoroquinolones and the risk of aortic diseases: a meta-analysis of observational studies.

BACKGROUND: Our aim was to determine the relationship between the use of fluoroquinolones and the risk of aortic diseases. METHODS: PubMed, EMBASE and the Web of Science were searched from inception to July 6, 2019, to identify observational studies that evaluated the risk of aortic diseases associated in users of fluoroquinolones compared with nonusers or users of other antibiotics. The primary outcome was the first occurrence of aortic diseases. We used the GRADE approach to rate the strength of evidence. We used the inverse variance method random-effect model to estimate the odds ratios (ORs) with 95% CIs, and statistical heterogeneity was assessed by the I2 statistic. RESULTS: This meta-analysis enrolled 2,829,385 patients reported the relationship between fluoroquinolones and the risk of aortic diseases. Compared with nonusers or users of other antibiotics, users of fluoroquinolone had a significantly increased risk of aortic diseases (adjusted OR, 2.10; 95% CI, 1.65-2.68; P = .000, I2 = 16.4%). The quality of evidence was moderate, and the number needed to harm (NNH) for aortic diseases among patients was estimated to be 1301. CONCLUSIONS: The fluoroquinolone use in patients significantly increases the risk of new-onset aortic diseases. Clinicians need to pay attention to these severe adverse events when considering fluoroquinolone use.

RNA-binding protein SFPQ cooperates with HDAC1 to suppress CD40 transcription in pulmonary adventitial fibroblasts.

Pulmonary artery adventitial fibroblasts, the most abundant cellular constituent of adventitia, are often the first to be activated and reprogrammed to then influence the tone and structure of the vessel wall in pulmonary arterial hypertension (PAH). Our previous study found that interruption of CD40 ligand (CD40L)-CD40 signaling improves the efficacy of transplanted endothelial progenitor cells in monocrotaline induced-PAH. However, whether CD40L-CD40 signaling is involved in the activation of adventitial fibroblasts in PAH and whether Drosophila behavior human splicing (DBHS) protein family members have any roles during adventitial fibroblasts activation are completely unclear. Here, we show that soluble CD40L (sCD40L) stimulation progressively increases pro-inflammatory activity, proliferation, and migration of pulmonary adventitial fibroblasts. Besides, sCD40L stimulation decreases splicing factor proline- and glutamine-rich protein (SFPQ) protein (one member of DBHS protein family) expression, while SFPQ overexpression suppresses sCD40L stimulation-induced proliferation and migration of pulmonary adventitial fibroblasts by repressing CD40 transcription. Moreover, ChIP assays found that sCD40L stimulation promotes histone H3 tri-methylation at lysine 4 (H3K4me3), H3K36me3, and H3K27 acetylation (H3K27ac) modifications on CD40 promoter region in pulmonary adventitial fibroblasts, while SFPQ overexpression decreases H3K36me3 modification and increases H3K36ac on CD40 promoter region by interacting with histone deacetylase-1 (HDAC1) to inhibit CD40 transcription. This in-depth study shows that CD40L-CD40 signaling promotes activation of pulmonary adventitial fibroblasts by increasing proliferation, migration, and pro-inflammatory activity of adventitial fibroblasts, and SFPQ could inhibit CD40 transcription though switching H3K36me3 to H3K36ac modifications on its promoter by interacting with HDAC1. This study, first, uncovers the roles of SFPQ on CD40L-CD40 signaling-mediated activation of pulmonary adventitial fibroblasts.

Correction: Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

[This corrects the article DOI: 10.18632/oncotarget.18138.].

Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPARγ Coactivator-1α (PGC-1α).

Purpose: Mitochondrial dysfunction in adipose tissue has emerged as key to the development of obesity and diabetes. Salvianolic acid B (SalB) is a water-soluble ingredient derived from Salvia miltiorrhiza that has been shown to possess potential anti-obese and anti-diabetic activities. However, the cellular mechanism of SalB on mitochondrial function with respect to these metabolic disorders has not been elucidated. Therefore, we aim to investigate the effects of SalB on mitochondrial function in 3T3-L1 adipocytes and analyze the underlying molecular mechanism. Methods: The effects of SalB on adipocyte differentiation, glucose uptake, and glycerol release were evaluated in 3T3-L1 adipocytes. Differentiated adipocytes were treated with SalB (50 µM) with or without PPARγ antagonist (GW9662, 20 µM) for 48 h, and mitochondrial oxygen consumption rate (OCR) as well as extracellular acidification rate (ECAR) were assessed using an XF Extracellular Flux Analyzer. The mitochondrial distribution of adipocytes was assessed using Mito Tracker Green (MTG) and observed under a fluorescent microscope. In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. Finally, changes in the protein levels of peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) were determined by western blotting and immunofluorescence analysis. Results: Treatment with SalB increased glucose uptake and mitochondrial respiration, reduced glycerol release and promoted adipocyte differentiation by increasing mRNA expression of adipogenic transcription factors including PPARγ, C/EBPα, and PPARα. Furthermore, SalB enhanced adipocytes mitochondrial content, mitochondrial respiration and glycolysis capacity, which had been attenuated by GW9662 treatment through the increased expression of PGC-1α. Conclusion: Our results provide novel insights into the role of PGC-1α and mitochondria as probable mediators of SalB activity in the regulation of adipocyte differentiation in 3T3-L1 adipocytes.

The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by Angiotensinâ ¡.

BACKGROUND/AIMS: Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms. METHODS: EPCs were cultured from bone marrow derived mononuclear cells. The effects of Ang Ⅱ on EPC proliferation, adhesion, migration, and in vitro tube formation were investigated using the MTT assay, adhesion assay, transwell chamber assay, and in vitro tube formation assay respectively. The underlying mechanisms were explored using Western blotting assay. RESULTS: EPC adhesion, migration and in vitro tube formation were promoted by Ang Ⅱ, and the effects were reversed by RhoA/Rho-associated kinases (ROCK) signaling pathway inhibitors including C3 exoenzyme, GGTI-286 and Y-27632. The active form of RhoA was up-regulated by Ang Ⅱ and this effect was abolished by C3 exoenzyme. Moreover, RhoA silencing resulted in a notable inhibition of EPC adhesion, migration and in vitro tube formation, suggesting that RhoA activation played a pivotal role in Ang Ⅱ angiogenic effect. The results also demonstrated that phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun-NH2 kinase was elevated by Ang Ⅱ and attenuated by C3 exoenzyme, GGTI-286 and Y-27632. The enhancing effects of Ang Ⅱ on EPC adhesion, migration and in vitro vasculogenesis were reversed by p38 inhibitor SB202190 and JNK inhibitor SP600125. CONCLUSION: Ang Ⅱ may enhance EPC neovascular-related functions through activating RhoA/ ROCK and MAPK signaling pathway.

Endothelial progenitor cells in age-related vascular remodeling.

Accumulating evidence has demonstrated that endothelial progenitor cells (EPCs) could facilitate the reendothelialization of injured arteries by replacing the dysfunctional endothelial cells, thereby suppressing the formation of neointima. Meanwhile, other findings suggest that EPCs may be involved in the pathogenesis of age-related vascular remodeling. This review is presented to summarize the characteristics of EPCs and age-related vascular remodeling. In addition, the role of EPCs in age-related vascular remodeling and possible solutions for improving the therapeutic effects of EPCs in the treatment of age-related diseases are discussed.

Proteomics Analysis of Testis of Rats Fed a High-Fat Diet.

BACKGROUND/AIMS: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. METHODS: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. RESULTS: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. CONCLUSION: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways.

AUXIN RESPONSE FACTOR3 Regulates Floral Meristem Determinacy by Repressing Cytokinin Biosynthesis and Signaling.

Successful floral meristem (FM) determinacy is critical for subsequent reproductive development and the plant life cycle. Although the phytohormones cytokinin and auxin interact to coregulate many aspects of plant development, whether and how cytokinin and auxin function in FM determinacy remain unclear. Here, we show that in Arabidopsis thaliana, cytokinin homeostasis is critical for FM determinacy. In this developmental context, auxin promotes the expression of AUXIN RESPONSE FACTOR3 (ARF3) to repress cytokinin activity. ARF3 directly represses the expression of ISOPENTENYLTRANSFERASE (IPT) family genes and indirectly represses LONELY GUY (LOG) family genes, both of which encode enzymes required for cytokinin biosynthesis. ARF3 also directly inhibits the expression of ARABIDOPSIS HISTIDINE KINASE4, a cytokinin receptor gene, resulting in reduced cytokinin activity. Consequently, ARF3 controls cell division by regulating cell cycle gene expression through cytokinin. In flowers, we show that AGAMOUS (AG) dynamically regulates the expression of ARF3 and IPTs, resulting in coordinated regulation of FM maintenance and termination through cell division. Moreover, genome-wide transcriptional profiling revealed both repressive and active roles for ARF3 in early flower development. Our findings establish a molecular link between AG and auxin/cytokinin and shed light on the mechanisms of stem cell maintenance and termination in the FM.

Association between cognitive vulnerability to depression - dysfunctional attitudes and glycaemic control among in-patients with type 2 diabetes in a hospital in Beijing: a multivariate regression analysis.

This cross-sectional study aimed to investigate the relationship between glycosylated haemoglobin (HbA1c) and cognitive vulnerability to depression (dysfunctional attitudes) in patients with type 2 diabetes mellitus. A total of 245 valid records from June 2016 to December 2016 were collected from a hospital in Beijing. Participants were asked to complete four questionnaires (Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Zung Self-rating Depression Scale, and World Health Organization Quality of Life Instrument-Short Form) to assess mental health and quality of life. Multivariate regression analysis was conducted to determine the correlations between HbA1c, mental health, quality of life and other clinical variables. The results showed that dysfunctional attitudes were associated with HbA1c, with a standardized regression coefficient (ß) of .13 (p = .01), although 1 h C-peptide (ß = -.75, p < .0001) was the most significant predictor of HbA1c in the regression model. The results indicated that dysfunctional attitudes, as a cognitive vulnerability to depression, were a relevant factor in HbA1c, although further studies are needed to establish the nature of the connection between dysfunctional attitudes and glycaemic control in diabetes patients.

Comparative analysis of proteomes between diabetic and normal human sperm: Insights into the effects of diabetes on male reproduction based on the regulation of mitochondria-related proteins.

This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1.2 or <0.83). According to gene ontology enrichment and pathway analyses, many of these differentially expressed proteins are associated with sperm function, including binding of sperm to the zona pellucida and proteasome function; of particular interest, half of these proteins were related to mitochondrial metabolism. Protein-interaction networks revealed that a decrease in Cystatin C and Dipeptidyl peptidase 4 in the mitochondria may be sources of the decreased motility of sperm from diabetic patients.

Jiang Tang Xiao Ke Granule Play an Anti-diabetic Role in Diabetic Mice Pancreatic Tissue by Regulating the mRNAs and MicroRNAs Associated with PI3K-Akt Signaling Pathway.

Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect. Methods: We used high fat diet (HFD) to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs) between JTXK-treated group (n = 6) and the diabetic group (n = 6) using MicroRNA (miRNA) Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6). Subsequently, miRNA target gene prediction, GO and Pathway analysis were used to explore the function of DEMs. Finally, the mechanism of anti-diabetic effects of JTXK granule was tested by in vitro INS-1 pancreatic ß-cell experiment. Results: The blood glucose and body weight of JTXK-treated group was significantly lower compared with the model group. Moreover, a total of 45 miRNAs with significant differences were detected in the model group and the JTXK-treated group (P ≤ 0.05, Fold Change > 2). Further, miRNA-mRNA analysis showed that the differential expression of mmu-miR-192-5p, mmu-miR-291a-3p, mmu-miR-320-3p, mmu-miR-139-5p and mmu-miR-378a-3p are closely related to pancreatic histological changes. In addition, pathway analysis showed that the DEMs were closely related to PI3K-Akt Signaling Pathway. Furthermore, the levels of serine/threonine-protein kinase (Akt), phosphorylated Akt (p-Akt) and phosphorylated forkhead transcription factor O1 (p-Foxo1) in INS-1-FOXO1 overexpressing model cells were lower than those in normal group, while JTXK granules could increase the expression of Akt, p-Akt and p-Foxo1. Conclusions: The results showed that JTXK granule could play an anti-diabetic role by regulating the mRNA and miRNAs associated with PI3K-Akt pathway in diabetic mice pancreatic tissue.

Relationships of circular RNA with diabetes and depression.

Type 2 diabetes mellitus (T2DM) is closely related to depression; however, the exact molecular mechnisms of this association are unknown. Here, we investigated whether circular RNAs (circRNAs) in the blood are related to the occurrence of depression in patients with T2DM. Fourteen patients with T2DM and depressive symptoms, as assessed by the Self-Rating Depression Scale, were included in this study. Cutoff points of 44 (total coarse points) and 55 (standard score) were used to define depression. The Patient Health Questionnaire 9 was used for common mental disorders, and a score of 5 or more the cutoff for depression. Microarray assays and quantitative real-time reverse transcription polymerase chain reaction showed that 183 hsa-circRNAs were significantly upregulated, whereas 64 were downregulated in the T2DM with depression group (p < 0.05) compared with that in the T2DM group. Differentially expressed hsa-circRNAs could interact with microRNAs to target mRNA expression. KEGG pathway analysis predicted that upregulation of hsa-circRNA_003251, hsa-circRNA_015115, hsa-circRNA_100918, and hsa_circRNA_001520 may participate in the thyroid hormone, Wnt, ErbB, and mitogen-activated protein kinase signalling pathways. We speculate that differentially expressed hsa-circRNAs could help us to clarify the pathogenesis of depression in patients with T2DM and could represent novel molecular targets for clinical diagnosis and therapy.

Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes.

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.