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1.
Jing Zhou MD Pengfei Wu MM Hongyu Sun MM Hong Zhou BM Yaolei Zhang BM Zhenliang Xiao MD 《Journal of cellular physiology》2020,235(3):2377-2388
This study aimed to examine whether lung tissue extracellular matrix (ECM) hydrogels have protective effects on radiation-induced lung injury (RILI). The cytocompatibility and histocompatibility were tested for the obtained ECM-derived hydrogel. Sprague–Dawley rats were randomly divided into three groups (n = 18): control group (control); rats receiving irradiation and intratracheal injection of normal saline (IR + NS); and rats receiving irradiation and intratracheal injection of lung ECM-derived hydrogel (IR + ECM). The wet/dry weight ratio was used to evaluate the congestion and edema of the lungs. Histopathological analysis of lung tissues was performed using hemotoxylin and eosin staining and Masson's trichrome staining. Immunohistochemical staining and western blot analyses were carried out to determine the expression of epithelial–mesenchymal transition (EMT)-related proteins in lung tissues (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin). In addition, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6), hydroxyproline, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were also evaluated. The ECM-derived hydrogels had good cytocompatibility and histocompatibility. ECM-derived hydrogel treatment improved lung histopathology injury and pulmonary edema. Higher expression of E-cadherin and lower expression of vimentin and α-SMA were found in the IR + ECM group compared with those in the IR + NS group. Hydroxyproline levels were reduced by ECM-derived hydrogel treatment compared with those in the IR + NS group. Obvious increases of TNF-α, IL-6, and TGF-β1 were identified following irradiation. Marked reductions in MDA content and increases in SOD were induced by ECM-derived hydrogel treatment in rats after radiation. ECM-derived hydrogels were shown to protect against RILI, potentially by reducing EMT, inflammation, and oxidative damage. 相似文献
2.
A model for shear stress sensing and transmission in vascular endothelial cells 总被引:3,自引:0,他引:3 下载免费PDF全文
Arterial endothelial cell (EC) responsiveness to flow is essential for normal vascular function and plays a role in the development of atherosclerosis. EC flow responses may involve sensing of the mechanical stimulus at the cell surface with subsequent transmission via cytoskeleton to intracellular transduction sites. We had previously modeled flow-induced deformation of EC-surface flow sensors represented as viscoelastic materials with standard linear solid behavior (Kelvin bodies). In the present article, we extend the analysis to arbitrary networks of viscoelastic structures connected in series and/or parallel. Application of the model to a system of two Kelvin bodies in parallel reveals that flow induces an instantaneous deformation followed by creeping to the asymptotic response. The force divides equally between the two bodies when they have identical viscoelastic properties. When one body is stiffer than the other, a larger fraction of the applied force is directed to the stiffer body. We have also probed the impact of steady and oscillatory flow on simple sensor-cytoskeleton-nucleus networks. The results demonstrated that, consistent with the experimentally observed temporal chronology of EC flow responses, the flow sensor attains its peak deformation faster than intracellular structures and the nucleus deforms more rapidly than cytoskeletal elements. The results have also revealed that a 1-Hz oscillatory flow induces significantly smaller deformations than steady flow. These results may provide insight into the mechanisms behind the experimental observations that a number of EC responses induced by steady flow are not induced by oscillatory flow. 相似文献
3.
van Beers JJ Raijmakers R Alexander LE Stammen-Vogelzangs J Lokate AM Heck AJ Schasfoort RB Pruijn GJ 《Arthritis research & therapy》2010,12(6):R219
Introduction
Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. 相似文献4.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献5.
We analyze the phenomenon of spreading of a Myxococcus xanthus bacterial colony on plates coated with nutrient. The bacteria spread by gliding on the surface. In the first few hours, cell
growth is irrelevant to colony spread. In this case, bacteria spread through peninsular protrusions from the edge of the initial
colony. We analyze the diffusion through the narrowing reticulum of cells on the surface mathematically and derive formulae
for the spreading rates. On the time scale of tens of hours, effective diffusion of the bacteria, combined with cell division
and growth, causes a constant linear increase in the colony's radius. Mathematical analysis and numerical solution of reaction-diffusion
equations describing the bacterial and nutrient dynamics demonstrate that, in this regime, the spreading rate is proportional
to the square root of both the effective diffusion coefficient and the nutrient concentration. The model predictions agree
with the data on spreading rate dependence on the type of gliding motility. 相似文献
6.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88
Background
Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.Methods
We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.Results
Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.Conclusions
Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.7.
Zachary Cooper Michael Greenwood Borbala Mazzag 《Bulletin of mathematical biology》2009,71(7):1543-1579
We investigate the role of heterogeneous expression of IP3R and RyR in generating diverse elementary Ca2+ signals. It has been shown empirically (Wojcikiewicz and Luo in Mol. Pharmacol. 53(4):656–662, 1998; Newton et al. in J. Biol. Chem. 269(46):28613–28619, 1994; Smedt et al. in Biochem. J. 322(Pt. 2):575–583, 1997) that tissues express various proportions of IP3 and RyR isoforms and this expression is dynamically regulated (Parrington et al. in Dev. Biol. 203(2):451–461, 1998; Fissore et al. in Biol. Reprod. 60(1):49–57, 1999; Tovey et al. in J. Cell Sci. 114(Pt. 22):3979–3989, 2001). Although many previous theoretical studies have investigated the dynamics of localized calcium release sites (Swillens
et al. in Proc. Natl. Acad. Sci. U.S.A. 96(24):13750–13755, 1999; Shuai and Jung in Proc. Natl. Acad. Sci. U.S.A. 100(2):506–510, 2003a; Shuai and Jung in Phys. Rev. E, Stat. Nonlinear Soft Matter Phys. 67(3 Pt. 1):031905, 2003b; Thul and Falcke in Biophys. J. 86(5):2660–2673, 2004; DeRemigio and Smith in Cell Calcium 38(2):73–86, 2005; Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005), so far all such studies focused on release sites consisting of identical channel types. We have extended an existing mathematical
model (Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005) to release sites with two (or more) receptor types, each with its distinct channel kinetics. Mathematically, the release
site is represented by a transition probability matrix for a collection of nonidentical stochastically gating channels coupled
through a shared Ca2+ domain. We demonstrate that under certain conditions a previously defined mean-field approximation of the coupling strength
does not accurately reproduce the release site dynamics. We develop a novel approximation and establish that its performance
in these instances is superior. We use this mathematical framework to study the effect of heterogeneity in the Ca2+-regulation of two colocalized channel types on the release site dynamics. We consider release sites consisting of channels
with both Ca2+-activation and inactivation (“four-state channels”) and channels with Ca2+-activation only (“two-state channels”) and show that for the appropriate parameter values, synchronous channel openings within
a release site with any proportion of two-state to four-state channels are possible, however, the larger the proportion of
two-state channels, the more sensitive the dynamics are to the exact spatial positioning of the channels and the distance
between channels. Specifically, the clustering of even a small number of two-state channels interferes with puff/spark termination
and increases puff durations or leads to a tonic response. 相似文献
8.
Goedkoop AY Kraan MC Picavet DI de Rie MA Teunissen MB Bos JD Tak PP 《Arthritis research & therapy》2004,6(4):R326-R334
Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To
evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic
lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable
methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab
(3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable
methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity
Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies
from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4.
Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and
the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI
was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 (P ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady
decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction
in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of αvβ3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant
reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend
toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab
treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration
and clinical improvement in psoriasis and psoriatic arthritis. 相似文献
9.
Background and aims
Legume species in the fynbos vegetation of the Cape Floristic Region, that fix N2 in soils with low P, may have evolved for enhanced acquisition and efficient use of P. It was hypothesized that N2-fixing and combined-N supplied (N-supplied) A. linearis, P. calyptrata and C. genistoides are adapted to low P and would be relatively unresponsive to increased P of 100 μM.Methods
18 legume species were evaluated for their nodulation response to low P availability. The N X P interaction was then examined in A. linearis, P. calyptrata and C. genistoides reliant on either N2-fixation or 300 μM N (NH4NO3), and receiving 0.1, 1.0, 10 and 100 μM P (NaH2PO4).Results
In the species selection experiment, A. linearis, P. calyptrata and C. genistoides, with the greatest nodule fresh weight (FW) and nodule FW to root FW ratio, were the most prolific nodulating species. In the N X P experiment, with low P supply, the biomass of N2-fixing P. calyptrata and C. genistoides was consistently greater than that of N-supplied plants. In contrast, with high P supply of 100 μM P, all N-supplied plants accumulated more biomass than the corresponding N2-fixing plants. High P-use efficiency, poor down-regulation of P uptake and P storage was evident in A. linearis and P. calyptrata.Conclusion
The growth response to P and the significant N X P interactions indicate that N2-fixing and N-supplied plants were not adapted to low P, but rather colimited by both N and P. 相似文献10.