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31.
KB Cullberg T Christiansen SK Paulsen JM Bruun SB Pedersen B Richelsen 《Obesity (Silver Spring, Md.)》2013,21(3):454-460
Background:
Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).Methods:
In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.Results:
Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.Conclusions:
Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation. 相似文献32.
Natalia J. Martinez Ganesha Rai Adam Yasgar Wendy A. Lea Hongmao Sun Yuhong Wang Diane K. Luci Shyh-Ming Yang Kana Nishihara Shunichi Takeda Mohiuddin Irina Earnshaw Tetsuya Okada Kazutoshi Mori Kelli Wilson Gregory J. Riggins Menghang Xia Maurizio Grimaldi Ajit Jadhav David J. Maloney Anton Simeonov 《PloS one》2016,11(11)
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34.
During the recent field visits to Saurashtra regions of Western India, one of the interesting fungi i.e. Trichaleurina javanica (Rehm) M. Carbone, Agnello & P. Alvarado (Chorioactidaceae, order Pezizales) was collected from Sarkhadiya Hanuman and Sasan (Gir Forest, India). Further confirmation of the identity was carried out by using molecular methods with its DNA barcoding. Review of literature showed that this species was previously reported from India under a different name; the collection here studied is the first one molecularly confirmed. Nucleotide sequence obtained during molecular analysis is submitted into NCBI and is the first record at BOLD data system for its DNA barcode (BOLD ID KSRF-0019). 相似文献
35.
Shyh-Ming Yang Makoto Yoshioka Jeffrey W. Strovel Daniel J. Urban Xin Hu Matthew D. Hall Ajit Jadhav David J. Maloney 《Bioorganic & medicinal chemistry letters》2019,29(10):1220-1226
Extensive optimization of quinazoline-based lead 8 is described. The structure-activity relationship studies indicate the S-configuration is preferred for the phenylmorpholine substitution. Together with incorporation of a (2-hydroxyl-2-methylpropyl)pyrazole moiety at the 2-position leads to analogs with comparable potency and marked improvement in the pharmacokinetic profile over our previously reported lead compounds. Further in vivo efficacy studies in Kasumi-1 xenograft mouse model demonstrates that the selected inhibitors are well tolerated and highly efficacious in the inhibition of tumor growth. Additionally, the representative analog 19 also demonstrated significant improvement of arthritis severity in a collagen-induced arthritis (CIA) mouse model. These results indicate potential use of these quinazoline-based BET inhibitors for treatment of cancer and inflammatory diseases. A brief discussion of the co-crystallized structure of 19 with BRD4 (BD1) is also highlighted. 相似文献
36.
Visceral leishmaniasis (VL) caused by Leishmania donovani is a major parasitic disease prevalent in endemic regions of Bihar in India. In the absence of good chemotherapeutic options, there is a need to develop an effective vaccine against VL which should be dependent on the generation of a T helper type 1 (Th1) immune response. We have shown that soluble proteins from promastigote of a new clinical isolate of L. donovani (2001) ranging from 68 to 97.4 kDa (F2 fraction), induce Th1 responses in the peripheral blood mononuclear cells of cured Leishmania patients and hamsters and also showed significant prophylactic potential. To understand the nature of F2 proteins, it was further characterized using 2-DE, MALDI-TOF and MALDI-TOF/TOF-MS. In all, 63 spots were cut from a CBB stained gel for analysis and data was retrieved for 52 spots. A total of 33 proteins were identified including six hypothetical/unknown proteins. Major immunostimulatory proteins were identified as elongation factor-2, p45, heat shock protein (HSP)70, HSP83, aldolase, enolase, triosephosphate isomerase, protein disulfideisomerase and calreticulin. This study substantiates the usefulness of proteomics in characterizing a complex protein fraction (F2) map of soluble L. donovani promastigote antigen identified as Th1 stimulatory for its potential as vaccine targets against VL. 相似文献
37.
A fractal analysis is used to analyze the influence of: (a) electrostatic interactions on binding and dissociation rate coefficients for antibodies HH8, HH10, and HH26 in solution to hen egg-white lysozyme (HEL) immobilized on a sensor chip surface [Biophys. J. 83 (2002) 2946]; and (b) the binding and dissociation of recombinant Fab in solution to random NHS-coupled Cys-HEL and oriented thiol-coupled Cys-HEL immobilized on a sensor chip surface [Methods 20 (2000) 310]. Single- and dual-fractal models were employed to fit the data. Values of the binding and the dissociation rate coefficient(s) and the fractal dimensions were obtained from a regression analysis provided by Corel Quattro Pro 8.0 (Corel Corporation Limited, Ottawa, Canada. 1997). The binding rate coefficients are quite sensitive to the degree of heterogeneity on the sensor chip surface. It is of interest to compare the results obtained by the fractal analysis with that of the original analysis [Biophys. J. 83 (2002) 2946]. For example, as one goes from the binding of 21 nM HH10/HEL to the binding of 640 nM HH10/HEL(K97A), Sinha et al. [Biophys. J. 83 (2002) 29461 indicate that the enhancement of diffusional encounter rates may be due to 'electrostatic steering' (a long-range interaction). Our analysis indicates that there is an increase in the value of the fractal dimension, Df1 by a factor of 1.12 from a value of 2.133-2.385. This increase in the degree of heterogeneity on the surface leads to an increase in the binding rate coefficient, k1 by a factor of 1.59 from 12.92 to 20.57. The fractal analysis of binding and dissociation of recombinant Fab in solution to random NHS-coupled Cys-HEL and oriented thiol-coupled Cys-HEL immobilized on a sensor chip [Methods 20 (2000) 310] surface are consistent with the degree of heterogeneity present on the sensor chip surface for the random and the oriented case. As expected, the random case will exhibit a higher degree of heterogeneity than the oriented case, leading to subsequently a higher binding rate coefficient. 相似文献
38.
Kamal A Ramu R Khanna GB Saxena AK Shanmugavel M Pandita RM 《Bioorganic & medicinal chemistry letters》2004,14(19):4907-4909
New pyrrolobenzodiazepine-anthraquinone hybrids have been designed and synthesized, found to effectively bind to DNA and also exhibit cytotoxicity against many cancer cell lines 相似文献
39.
The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, yet the mechanisms underlying these effects have remained elusive. Since Nef likely functions as an adaptor protein, we exploited a proteomic approach to directly identify molecules that Nef targets to subvert the signaling machinery in T cells. We purified to near homogeneity a major Nef-associated protein complex from T cells and identified by mass spectroscopy its subunits as DOCK2–ELMO1, a key activator of Rac in antigen- and chemokine-initiated signaling pathways, and Rac. We show that Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2–ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Our data indicate that Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses. 相似文献
40.