scholarly journals Molecular Biomarkers for Weight Control in Obese Individuals Subjected to a Multiphase Dietary Intervention

2017 ◽  
Vol 102 (8) ◽  
pp. 2751-2761 ◽  
Author(s):  
Jennifer Bolton ◽  
Emilie Montastier ◽  
Jérôme Carayol ◽  
Sophie Bonnel ◽  
Lucile Mir ◽  
...  

Abstract Context Although calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals. Objective To identify biomarkers of successful weight control during a dietary intervention (DI). Design, Setting, and Participants Adipose tissue (AT) transcriptomes were compared between 21 obese individuals who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzyme-linked immunosorbent assay. Intervention Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet. Outcome Measure Weight changes at the end of the DI. Results We evaluated six genes that had altered expression during DI, encode secreted proteins, and have not previously been implicated in weight control (EGFL6, FSTL3, CRYAB, TNMD, SPARC, IGFBP3), as well as genes for which baseline expression differed between those with good and poor weight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored AT messenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified in which transforming growth factor β1 (TGF-β1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-β1 inhibitor. Conclusions We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.

2016 ◽  
Vol 36 (8) ◽  
pp. 802-812 ◽  
Author(s):  
XH Chang ◽  
A Zhu ◽  
FF Liu ◽  
LY Zou ◽  
L Su ◽  
...  

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200–240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.


2006 ◽  
Vol 76 (6) ◽  
pp. 367-376 ◽  
Author(s):  
Ortega ◽  
Rodríguez-Rodríguez ◽  
Aparicio ◽  
Marín-Arias ◽  
López-Sobaler

The fight against excess weight and obesity is a health priority. The aim of this study was to analyze the anthropometric changes induced by two weight control programs based on approximating the diet to the theoretical ideal (increasing the consumption of foods with the largest differences between the recommended and observed intakes: cereals and vegetables – for which a minimum of 6 and 3 servings/day are recommended, respectively). The study subjects were 57 Spanish women with a body-mass index (BMI) of 24–35 kg/m², all of whom were randomly assigned to one of two slightly hypocaloric diets for a six-week period: diet V, in which the consumption of greens and vegetables was increased, or diet C, in which the consumption of cereals was increased. Dietetic and anthropometric data were collected at the start of the study and again at two and six weeks. The dietary intervention approximated the subjects’ energy provision from proteins, fats, and carbohydrates to those recommended. The Healthy Eating Index (HEI) improved with both diets. Reductions in body weight, BMI, and the amount of body fat (kg) were also achieved with both diets. Weight loss was 1.56 ± 0.93 kg and 1.02 ± 0.55 kg at two weeks with diet C and V respectively, and 2.8 ± 1.4 kg and 2.0 ± 1.3 kg at six weeks (p < 0.05). Approximating the diet to the theoretical ideal by increasing the consumption of vegetables or cereals may therefore be of use in weight control. In terms of weight loss and the improvement of the diet quality (energy profile and HEI), diet C was significantly more effective than diet V.


Author(s):  
Sritharadol Rutthapol ◽  
Chunhachaichana Charisopon ◽  
Kumlungmak Sukanjana ◽  
Buatong Wilaiporn ◽  
Dechraksa Janwit ◽  
...  

ABSTRACT This study evaluated the effect of mupirocin topical spray on burn wound healing in a rat model. Fifteen male Sprague Dawley rats were used to create full-thickness burns on the rat dorsum using a cylindrical stainless steel rod. The rats were topically treated with normal saline solution (NSS), mupirocin spray, ointment, and solution. The wound size and morphological evaluation were investigated by photographs and clinical criterions for wound healing. The histology was observed by hematoxylin and eosin (HandE) staining assay. The immunohistochemical study was evaluated by detection of transforming growth factor-beta 1 (TGF-β1), and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of matrix metalloproteinase-1 (MMP-9/TIMP-1) was quantified using the enzyme-linked immunosorbent assay (ELISA) assay. A complete healing was observed at 28 days in all treatments. Mupirocin formulations accelerated the wound healing faster than NSS in size. However, the clinical criteria indicated a desirable skin appearance in the mupirocin spray and ointment treated groups. The histological evaluations showed no differences between the treatments while the immunohistochemical study revealed that all treatments reduced the level of TGF-β1 over time, particularly on day 28 in the mupirocin spray and ointment treated groups. The MMP-9/TIMP-1 ratio was significantly lower in the mupirocin spray and ointment treated groups than in the NSS and mupirocin solution groups. This study shows the safety and efficacy in the use of mupirocin topical spray. The topical mupirocin spray is an alternative suitable for development as a human topical anti-infective and wound protection spray.


2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hong-Xing Liao ◽  
Zhi-Hui Zhang ◽  
Hui-Lin Chen ◽  
Ying-Mei Huang ◽  
Zhan-Liang Liu ◽  
...  

Abstract Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.


Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


2011 ◽  
Vol 301 (4) ◽  
pp. F793-F801 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Shanzhong Yang ◽  
Edward Abraham ◽  
Anupam Agarwal ◽  
Gang Liu

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.


2016 ◽  
Vol 29 (4) ◽  
pp. 696-706 ◽  
Author(s):  
Jun Shi ◽  
Yu Liu ◽  
Shihai Yan ◽  
Daonan Yan

Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided into six groups (normal control, model control, YWF at low dose, YWF at median dose, YWF at high dose, and loratadine). Rats were injected with antigen for sensitization. Then, rats in the YWF groups were treated with different dose of YWF for 28 days. Loratadine was used as a positive control. Number of sneezes, degree of runny nose, nasal rubbing movements, and tissue damage were scored. The protein and mRNA expression of Foxp3 were determined by western blot and real time-PCR analysis, respectively. Flow cytometry was used to detect the number of CD4+CD25+Foxp3+ Treg cells. The content of interleukin (IL)-10, transforming growth factor β1 (TGF-β1), IL-13, and IL-4 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Scores of symptoms were significantly reduced and nasal mucosa damage was alleviated after YWF administration. YWF increased the expression of Foxp3, IL-10, TGF-β1, and number of CD4+CD25+Foxp3+ Treg cells which were reduced by antigen injection. The expression levels of IL-13 and IL-4 were increased after antigen administration while decreased after YWF treatment. YWF may ameliorate AR through inhibiting inflammatory response and promoting Foxp3 expression.


2018 ◽  
Vol 3 (2) ◽  
pp. 200-212 ◽  
Author(s):  
Brendan M Giles ◽  
Timothy T Underwood ◽  
Karim A Benhadji ◽  
Diana K S Nelson ◽  
Lisa M Grobeck ◽  
...  

Abstract Background The transforming growth factor β (TGF-β)–signaling pathway has emerged as a promising therapeutic target for many disease states including hepatocellular carcinoma (HCC). Because of the pleiotropic effects of this pathway, patient selection and monitoring may be important. TGF-β1 is the most prevalent isoform, and an assay to measure plasma levels of TGF-β1 would provide a rational biomarker to assist with patient selection. Therefore, the objective of this study was to analytically validate a colorimetric ELISA for the quantification of TGF-β1 in human plasma. Methods A colorimetric sandwich ELISA for TGF-β1 was analytically validated per Clinical and Laboratory Standards Institute protocols by assessment of precision, linearity, interfering substances, and stability. A reference range for plasma TGF-β1 was established for apparently healthy individuals and potential applicability was demonstrated in HCC patients. Results Precision was assessed for samples ranging from 633 to 10822 pg/mL, with total variance ranging from 28.4% to 7.2%. The assay was linear across the entire measuring range, and no interference of common blood components or similar molecules was observed. For apparently healthy individuals, the average TGF-β1 level was 1985 ± 1488 pg/mL compared to 4243 ± 2003 pg/mL for HCC patients. Additionally, the TGF-β1 level in plasma samples was demonstrated to be stable across all conditions tested, including multiple freeze–thaw cycles. Conclusions The ELISA described in this report is suitable for the quantification of TGF-β1 in human plasma and for investigational use in an approved clinical study.


2016 ◽  
Vol 45 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Matthias Kieb ◽  
Frank Sander ◽  
Cornelia Prinz ◽  
Stefanie Adam ◽  
Anett Mau-Möller ◽  
...  

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.


2018 ◽  
Vol 46 (5) ◽  
pp. 2056-2071 ◽  
Author(s):  
Long Zheng ◽  
Long Li ◽  
Guisheng Qi ◽  
Mushuang Hu ◽  
Chao Hu ◽  
...  

Background/Aims: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. Methods: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-β1 and various growth factors. Results: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-β1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. Conclusion: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.


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