Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins

Objective—We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Approach and Results—Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Conclusions—Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction

Advances in Understanding the Role Mechanism of Dietary Fiber in Mitigating Colitis

Colitis is an inflammatory intestinal disease that lasts for a long time, has an unknown cause, and occurs repeatedly. It is usually accompanied by symptoms such as intestinal cell damage, intestinal immunity, and abnormal intestinal flora. Numerous studies have shown that dietary fiber, as a prebiotic, its metabolites can selectively improve the composition of the intestinal flora, which in turn improves the level of intestinal short-chain fatty acids, reduces the expression of inflammatory factors, and enhances the function of the intestinal immune barrier, thereby improving the inflammatory response of the organism. This anti-inflammatory effect of dietary fiber through its metabolites provides new research ideas to assist in the treatment of colitis. This paper outlines the pathogenesis of colitis, and the mechanism of interaction between dietary fiber and its metabolites with intestinal flora, inflammatory factors and immune cells, aiming to provide theoretical basis for the alleviation of colitis by dietary fiber and the development of functional foods

Weight change during chemotherapy changes the prognosis in non metastatic breast cancer for the worse

<p>Abstract</p> <p>Background</p> <p>Weight change during chemotherapy is reported to be associated with a worse prognosis in breast cancer patients, both with weight gain and weight loss. However, most studies were conducted prior to the common use of anthracycline-base chemotherapy and on North American populations with a mean BMI classified as overweight. Our study was aimed to evaluate the prognostic value of weight change during anthracycline-based chemotherapy on non metastatic breast cancer (European population) with a long term follow-up.</p> <p>Methods</p> <p>Patients included 111 women diagnosed with early stage breast cancer and locally advanced breast cancer who have been treated by anthracycline-based chemotherapy regimen between 1976 and 1989. The relative percent weight variation (WV) between baseline and postchemotherapy treatment was calculated and categorized into either weight change (WV > 5%) or stable (WV < 5%). The median follow-up was 20.4 years [19.4 - 27.6]. Cox proportional hazard models were used to evaluate any potential association of weight change and known prognostic factors with the time to recurrence and overall survival.</p> <p>Results</p> <p>Baseline BMI was 24.4 kg/m2 [17.1 - 40.5]. During chemotherapy treatment, 31% of patients presented a notable weight variation which was greater than 5% of their initial weight.</p> <p>In multivariate analyses, weight change (> 5%) was positively associated with an increased risk of both recurrence (RR 2.28; 95% CI: 1.29-4.03) and death (RR 2.11; 95% CI: 1.21-3.66).</p> <p>Conclusions</p> <p>Our results suggest that weight change during breast-cancer chemotherapy treatment may be related to poorer prognosis with higher reccurence and higher mortality in comparison to women who maintained their weight.</p

Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators

BACKGROUND: The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. METHOD: A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. RESULTS: A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D(1 )overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. CONCLUSION: Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D(1 )and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results

Substrate effects in the supramolecular assembly of 1,3,5-benzene tricarboxylic acid on graphite and graphene

The behavior of small molecules on a surface depends critically on both molecule–substrate and intermolecular interactions. We present here a detailed comparative investigation of 1,3,5-benzene tricarboxylic acid (trimesic acid, TMA) on two different surfaces: highly oriented pyrolytic graphite (HOPG) and single-layer graphene (SLG) grown on a polycrystalline Cu foil. On the basis of high-resolution scanning tunnelling microscopy (STM) images, we show that the epitaxy matrix for the hexagonal TMA chicken wire phase is identical on these two surfaces, and, using density functional theory (DFT) with a non-local van der Waals correlation contribution, we identify the most energetically favorable adsorption geometries. Simulated STM images based on these calculations suggest that the TMA lattice can stably adsorb on sites other than those identified to maximize binding interactions with the substrate. This is consistent with our net energy calculations that suggest that intermolecular interactions (TMA–TMA dimer bonding) are dominant over TMA–substrate interactions in stabilizing the system. STM images demonstrate the robustness of the TMA films on SLG, where the molecular network extends across the variable topography of the SLG substrates and remains intact after rinsing and drying the films. These results help to elucidate molecular behavior on SLG and suggest significant similarities between adsorption on HOPG and SLG

Planar Anchoring of C 70

The surface‐induced anchoring effect is a well‐developed technique to control the growth of liquid crystals (LCs). Nevertheless, a defined nanometer‐scale template has never been used to induce the anchored growth of LCs with molecular building units. Scanning tunneling microscopy results at the solid/liquid interface reveal that a 2D covalent organic framework (COF‐1) can offer an anchoring effect to template C70 molecules into forming several LC mesophases, which cannot be obtained under other conditions. Through comparison with the C60 system, a stepwise breakdown in ordering of C70 LC is observed. The process is described in terms of the effects of molecular anisotropy on the epitaxial growth of molecular crystals. The results suggest that using a surface‐confined template to anchor the initial layer of LC molecules can be a modular and potentially broadly applicable approach for organizing molecular mesogens into LCs

Self-assembly of indole-2-carboxylic acid at graphite and gold surfaces

Model systems are critical to our understanding of self-assembly processes. As such, we have studied the surface self-assembly of a small and simple molecule, indole-2-carboxylic acid (I2CA). We combine density functional theory gas-phase (DFT) calculations with scanning tunneling microscopy to reveal details of I2CA assembly in two different solvents at the solution/solid interface, and on Au(111) in ultrahigh vacuum (UHV). In UHV and at the trichlorobenzene/highly oriented pyrolytic graphite (HOPG) interface, I2CA forms epitaxial lamellar structures based on cyclic OH⋯O carboxylic dimers. The structure formed at the heptanoic acid/HOPG interface is different and can be interpreted in a model where heptanoic acid molecules co-adsorb on the substrate with the I2CA, forming a bicomponent commensurate unit cell. DFT calculations of dimer energetics elucidate the basic building blocks of these structures, whereas calculations of periodic two-dimensional assemblies reveal the epitaxial effects introduced by the different substrates

Template-driven dense packing of pentagonal molecules in monolayer films

The integration of molecules with irregular shape into a long-range, dense and periodic lattice represents a unique challenge for the fabrication of engineered molecular scale architectures. The tiling of pentagonal molecules on a two-dimensional (2D) plane can be used as a proof-of-principle investigation to overcome this problem because basic geometry dictates that a 2D surface cannot be filled with a periodic arrangement of pentagons, a fundamental limitation that suggests that pentagonal molecules may not be suitable as building blocks for dense films. However, here we show that the 2D covalent organic framework (COF) known as COF-1 can direct the growth of pentagonal guest molecules as dense crystalline films at the solution/solid interface. We find that the pentagonal molecule corannulene adsorbs at two different sites on the COF-1 lattice, and that multiple molecules can adsorb into well-defined clusters patterned by the COF. Two types of these dense periodic packing motifs lead to a five-fold symmetry reduction compatible with translational symmetry, one of which gives an unprecedented high molecular density of 2.12 molecules/nm2