Search

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes.

Molecular hybridization is considered as an effective tactic to develop drugs for the treatment of cancer. A series of novel hybrid compounds of isatin and Michael acceptor were designed and synthesized on the basis of association principle. These hybrid compounds were tested for cytotoxic potential against human cancer cell lines namely, BGC-823, SGC-7901 and NCI-H460 by MTT assay. Most compounds showed good anti-growth activities in all tested human cancer cells. SAR and QSAR analysis may provide vital information for the future development of novel anti-cancer inhibitors. Notably, compound 6a showed potent growth inhibition on BGC-823, SGC-7901 and NCI-H460 with the IC50 values of 3.6 ± 0.6, 5.7 ± 1.2, 3.2 ± 0.7 μM, respectively. Besides, colony formation assays, wound healing assays and flow cytometry analysis indicated 6a exhibited a potent anti-growth and anti-migration ability in a concentration-dependence manner through arrested cells in the G2/M phase of cell cycle. Moreover, 6a significantly repressed tumor growth in a NCI-H460 xenograft mouse model. Overall, our findings suggested isatin analogues inspired Michael acceptor may provide promising lead compounds for the development of cancer chemotherapeutics.

To gain insight into the effect of metformin on losing weight from peptidomic perspective and to screen potential active peptides for reducing fat lipid deposition. After determining the proper concentration of metformin on human primary visceral adipocytes, we constructed a comparative peptidomic profiling between control and metformin treatment group (n = 3) using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by liquid chromatography tandem mass spectrometry. We identified and quantified 3065 non-redundant peptides, 304 of which were differentially expressed after metformin treatment, 206 peptides were up regulated and 98 peptides were down regulated significantly. Gene ontology (GO) enrichment and pathway analysis were performed to study differentially peptides though their precursor proteins. We concluded three peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for obesity. On one hand, these results confirmed the versatile effects of metformin on adipocyte and advance our current understanding of metformin, on the other hand, these identified peptides might play putative roles in treatment of obesity.

Our previous study revealed that miR‑148a, a cyclic adenosine monophosphate‑response element binding protein‑modulated microRNA that promotes adipocyte differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects and a mouse model. The present study investigated the expression of miR‑148a in human adipose tissue‑derived mesenchymal stem cells (hMSCs‑Ad) in response to inflammatory cytokines and adipokines to clarify its underlying mechanism. miR‑148a expression was detected using reverse transcription‑quantitative polymerase chain reaction analysis and its promoter activity was detected with a luciferase assay. miR‑148a expression levels decreased when differentiated hMSCs‑Ad were exposed to inflammatory cytokines or adipokines, which suggested that miR‑148a may be important in adipocyte metabolism and inflammation. Furthermore, the promoter activity of miR‑148a decreased following treatment of cells with inflammatory cytokines or adipokines. The results of the present study indicated a novel role of miR‑148a in adipocyte inflammation; therefore, miR‑148a may be involved in obesity complications via its own underlying transcriptional mechanism.

Obesity rates have risen rapidly over the past several decades and obesity is now a global public health challenge. The reduction of excessive adipogenesis is thought to be an effective intervention for obesity and obesity-related metabolic diseases such as type 2 diabetes. In this study, a novel peptide PDBSN was identified that functions to suppress adipogenesis. In both human preadipocytes and mouse adipose-derived stem cells (ADSCs), PDBSN exhibited a suppressive effect on the accumulation of lipids and the expression of genes as well as their corresponding proteins (CCAAT/enhancer binding protein (C/EBP)β, C/EBPα and nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ)) relevant to adipogenic cell differentiation. Although adipogenesis decreased, the preadipocyte number and proliferation were not influenced by the PDBSN treatment. Apoptosis and the cell cycle were also determined to not have a role in the action of PDBSN. Mechanistically, the activity of the AMPK (adenosine 5'-monophosphate-activated protein kinase) pathway was markedly increased upon PDBSN treatment. Moreover, treatment of preadipocytes with compound C, a selective AMPK inhibitor, abolished the effect of PDBSN in anti-adipogenesis, suggesting that the function of PDBSN relied on the AMPK pathway. These results suggest an effective role for PDBSN in suppressing adipogenesis and show potential for anti-obesity drug discovery.

In Zhang’s recent works, a second-order Mehrotra-type predictor-corrector algorithm for linear optimization was extended to semidefinite optimization and derived that the algorithm for semidefinite optimization had O(n 3/2log(X 0)T•S 0/e) iteration complexity based on the NT direction as Newton search direction. In this paper, we extend the second-order Mehrotra-type predictor-corrector algorithm for linear optimization to semidefinite optimization and discuss the polynomial convergence of the algorithm by modifying the corrector direction and new iterates. It is proved that the iteration complexity is reduced to O(nlogX 0•S 0/e), which coincides with the currently best iteration bound of Mehrotra-type predictor-corrector algorithm for semidefinite optimization.

MicroRNAs (miRNAs) have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism, adipocyte differentiation. To determine the role of adipogenic miRNAs in the adipocyte differentiation process, we used microarray technology to monitor miRNA levels in human adipose-derived mesenchymal stem cells (hMSCs-Ad), human stromal vascular cells (SVCs) and differentiated adipocytes. 79 miRNAs were found to be differentially expressed, most of which are located in obesity related chromosomal regions but have not been previously linked to adipocyte differentiation process. A systematic search was made for relevant studies in academic data bases, involving the Gene Expression Omnibus (GEO) ArrayExpress, Pubmed and Embase database. Eight studies on human adipocyte differentiation or obesity were included in the final analysis. After combining our microarray data with meta-analysis of published microarray data, we detected 42 differently expressed miRNAs (meta-signature miRNAs) in mature adipocytes compared to SVCs or hMSCs-Ad. Our study shows meta-signature miRNAs specific for adipogenesis, several of which are correlated with key gene targets demonstrating functional relationships to pathways in BMP signaling pathway, Cell differentiation, Wnt signaling, insulin receptor signaling pathway, MAPK signaling, Cell cycle and lipid metabolic process. Our study shows that the first evidence of hsa-let-7 family, hsa-miR-15a-5p, hsa-miR-27a-3p, hsa-miR-106b-5p, hsa-miR-148a-3p and hsa-miR-26b-5p got a great weight in adipogenesis. We concluded that meta-signature miRNAs involved in adipocyte differentiation and provided pathophysiological roles and novel insight into obesity and its related metabolic diseases.

Re-fracture risk is higher following osteoporotic fracture. However, there is no accurately reported rate of re-fracture incidence in southwest China. The purpose of this study was to describe the osteoporotic vertebral fracture (OVF) survival for re-fracture state and analyze the risk of re-fracture. This historical cohort study was conducted in four hospitals in southwest China. Patients aged ≥ 50 years (n = 586) with OVF who were supposed to receive anti-osteoporosis drugs after the fracture were included (2012–2017). Telephone follow-up and referring case files were used to estimate the survival for re-fracture and identify the determinants of re-fracture. A total of 555 patients completed the follow-up investigation. Overall, 285 patients experienced a re-fracture, and the longest follow-up investigation time was 72 months. The survival rates for re-fracture at 12 months, 24 months, 36 months, and 48 months were 82.0%, 71.5%, 61.7%, and 34.0%, respectively. The factors correlated with re-fracture hazard were advanced age [hazard ratio (HR) = 1.996], being female (HR = 1.342), smoking (HR = 1.435), history of hypertension (HR = 1.219) and diabetes (HR = 3.271), and persistence of taking anti-osteoporosis drugs after fracture [0–3 months, 4–6 months, 7–12 months, and more than 12 months (HR = 0.703)]. OVF patients with advanced age, who were female, smoked, had fracture with hypertension or diabetes, and who complied poorly with anti-osteoporosis drug treatment presented higher prevalence of re-fracture and low anti-osteoporosis adherence in southwest China. The management of anti-osteoporosis after fracture is necessary in this area.

Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes' metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders.

In recent years, the economic viability of large-scale shale-gas exploration and development projects has been impacted directly by improvements in horizontal-well drilling and hydraulic-fracturing technologies. However, results from multiple shale-gas projects indicate that accurate reservoir descriptions and resulting predictions of sweet spots are also crucial to maximize production from those projects. Accurate reservoir description results in the most appropriate placement of well locations and trajectories, hydraulic-fracture design, and reservoir engineering. The successful experience in shale-gas exploration and development outside China can aid in the search for the most favorable geologic characteristics and rock-physical properties and the examination of appropriate well-log interpretation and seismic-reservoir-prediction technologies for a shale-gas study in the eastern area of Sichuan Basin, China. Favorable parameters in a shale-gas reservoir are mid- to high kerogen content, low clay volumes, high brittleness, high effective porosity, and high permeability, along with well-developed microfractures. Of those parameters, mid- to high total organic carbon (TOC) is favorable for shale-gas accumulation, and high brittleness is beneficial to hydraulic-fracture propagation. Hence, the aim is to find sweet spots with high TOC and high brittleness. Starting with petrophysical analyses that combine laboratory measurements, core data, and well logs, a statistical model is used to estimate relative volumes and compositions of TOC and minerals and to establish a qualitative evaluation criterion for shale-gas reservoirs in this area. Petrophysical modeling and rock-property analyses establish the relationship among petrophysical properties (such as TOC, effective porosity, and gas saturation) and elastic properties (such as P-impedance, VP/VS ratio, Poisson's ratio, and Young's modulus) of the formation, which are related to brittleness. Rock-property analysis, prestack simultaneous inversion, and facies-fluid probability-analysis technologies help to predict favorable development zones for the shale-gas reservoir. Finally, the values of brittleness, TOC, and shale-gas lithology volume are combined to predict the sweet spots of the gas shale and to guide subsequent developments.

In the Original publication of the article, the funding ID has been incorrectly published as (815602390) in the Acknowledgements.

Food intolerance is believed to be a source of frequent medical problems in ulcerative colitis (UC), which closely correlate with patients' dietary pattern. Living in an underdeveloped area of China, residents in southwestern region have diverse dietary habits. The objective of this study is to determine the prevalence of food intolerance in the UC patients in this area and to discuss some of the possible risk factors leading to the condition.Food antibodies in serum of 80 patients with active UC were determined by standard enzyme-linked immuno sorbent assay (ELISA). This study examined the risk factors contributing to high titers of food antibodies and the dietary patterns correlating with food intolerance in these demographics.83.8% of patients (67/80) were found to be seropositive for food intolerance. Patients of female, aged between 20 to 40 and the one who tended to have a high fat diet were tested to be highly seropositive (p0.05). Neither spicy food intake nor the course the disease manifested any relationship with the presence of food intolerance (p0.05).Active UC patients in southwestern region of China have showed to be high seropositive in food intolerance, particularly in female and young patients. Dietary patterns with high in fat intake seem to have caused high prevalence of seropositivity in food intolerance. Although rice has been taken as staple food and the spicy food has been popular among citizen in this region, these foods have indicated to no effect on food intolerance in this study.背景与目的：溃疡性结肠炎与患者的饮食模式密切相关，食物不耐受被认为 是溃疡性结肠炎患者频繁就医的原因。生活在中国欠发达地区，中国西南地区 居民有着不同的饮食习惯。本研究的目的是确定中国西南地区急性溃疡性结肠 炎患者食物不耐受的患病率，并探讨导致该情况的可能危险因素。方法与研 究设计：运用酶联免疫法检测80 名急性期溃疡性结肠炎患者血清特定食物抗 体水平，通过调查问卷获取患者饮食模式及人口学资料并分析。结果：本研 究83.8%（67/80）患者食物不耐受检测阳性，年龄介于20 至40 岁倾向于高 脂饮食的女性患者血清食物抗体水平明显高（p0.05)，主食种类、辛辣饮 食、病史等因素组间差别无统计学意义（p0.05)。结论：中国西南地区急性 溃疡性结肠炎患者食物不耐受阳性率高，尤以女性及中青年患者明显。高脂饮 食模式与食物不耐受显著相关。本研究未发现桂西地区以大米为主食、喜食辛 辣等饮食习惯与患者食物不耐受情况有明显联系。.

Excessive adipocyte differentiation and proliferation are closely associated with the onset of obesity, which has been partially linked to microRNA expression. In previous studies, using miRNA microarray screening, we found that miR-1275 was significantly decreased in human mature adipocytes. In this study, we examined the role of miR-1275 in adipogenesis. Our results indicated that miR-1275 can inhibit the differentiation of human visceral preadipocytes without affecting their proliferation. ELK1, an E-twenty-six (ETS)-domain transcription factor associated with adipocyte differentiation, was strongly suppressed by miR-1275 in human visceral adipocytes. This was demonstrated via a dual-luciferase reporter assay and pointed to ELK1 as a direct target of miR-1275. Furthermore, miR-1275 expression was significantly diminished in the visceral adipose tissue of overweight and obese human subjects accompanied by a negative correlation with body mass index. These results suggest that miR-1275 could play a future role in the management of obesity, as a novel therapeutic target or biomarker.

MicroRNAs (miRNAs) have emerged as epigenetic regulators of metabolism and energy homeostasis. There is a growing body of evidence pointing to miRNAs that have important regulatory roles in insulin sensitivity. The aim of this work was to explore the expression and mechanism of action of miR-26b in obesity-related insulin resistance (IR) in adipocytes. Quantitative real-time PCR was performed to determine miR-26b expression in obese rodent models, human obesity subjects and insulin-resistant adipocytes. We analysed the roles of miR-26b overexpression and inhibition on glucose uptake in adipocytes. Western blotting was used to detect the levels of protein molecules involved in the phosphoinositide-3-kinase (PI3K) pathway. Bioinformatics and the Dual Luciferase Assay were used to identify the target gene of miR-26b. We assessed the regulatory roles of miR-26b on the phosphatase and tensin homologue (PTEN)/PI3K/AKT pathway and the relationship between miR-26b and the metabolism of human obese subjects. Levels of miR-26b are reduced in visceral adipose tissue (VAT) in obese rodent models, human obesity and insulin-resistant adipocytes. MiR-26b promotes insulin-stimulated glucose uptake and increases insulin-stimulated glucose transporter type 4 translocation to the plasma membrane in human mature adipocytes. MiR-26b modulates insulin-stimulated AKT activation via inhibition of its target gene, PTEN, and significantly increases insulin sensitivity via the PTEN/PI3K/AKT pathway. The expression level of miR-26b negatively correlates with increasing body mass index and homeostasis model assessment for IR in human obese subjects. Decreased miR-26b expression in VAT may be involved in obesity-related IR by interrupting the PTEN/PI3K/AKT pathway.

Visceral obesity is an independent risk factor for metabolic syndrome, and abnormal fat accumulation is linked to increases in the number and size of adipocytes. MiR-146b was a miRNA highly expressed in mature adipocytes while very lowly expressed in human mesenchymal stem cells (hMSCs) and human visceral preadipocytes (vHPA). In this paper, we mainly focused on the roles of miR-146b in adipogenesis. We found miR-146b could inhibit the proliferation of visceral preadipocytes and promote their differentiation. MiR-146b in human visceral adipocytes inhibited the expression of KLF7, a member of the Kruppel-like transcription factors, as demonstrated by a firefly luciferase reporter assay, indicating that KLF7 is a direct target of the endogenous miR-146b. MiR-146b expression was significantly altered in visceral and subcutaneous adipose tissues in human overweight and obese subjects, and in the epididymal fat tissues and brown fat tissues of diet-induced obese mice. Our data indicates that miR-146b may be a new therapeutic target against human visceral obesity and metabolic dysfunction.