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141.
Introduction
Osteoarthritis (OA) is associated with chronic inflammation, and mesenchymal stromal cells (MSCs) have been shown to provide pain relief and reparative effects in clinical investigations. MSCs are often delivered with hyaluronic acid (HA), although the combined mechanism of action is not fully understood; we thus investigated the immunomodulatory effects of combining MSCs with different molecular weights (MW) of HA.Methods
HAs with MWs of 1.6 MDa (hHA), 150 kDa or 7.5 kDa, were added to MSCs alone or MSC-immune cell co-cultures. Gene expression analyses, flow cytometry and cytokine measurements were assessed to determine the effect of HAs on the MSC interactions with immune cells.Results
MSCs in the presence of HAs, in both normal and lymphocyte-conditioned medium, showed negligible changes in gene expression. While addition of hHA resulted in increased proliferation of activated lymphocytes, both in the presence and absence of MSCs, the overall combined effect was a more regulated, homeostatic one; this was supported by higher ratios of secreted IL10/IFNγ and IL10/IL2, in lymphocyte cultures, than with lower MW HAs or no HA, both in the presence and absence of MSCs. In addition, examination of monocyte-derived macrophages showed an increased M2 macrophage frequency (CD14+CD163+CD206+) in the presence of hHA, both with and without MSCs.Conclusions
hHA produces a less pro-inflammatory environment than lower MW HAs. Moreover, combining hHA with MSCs has an additive effect on the MSC-mediated immunomodulation, suggestive of a more potent combination treatment modality for OA. 相似文献142.
143.
Sowmya Vanguru Lavanya Jilla Yasodakrishna Sajja Rajashaker Bantu Lingaiah Nagarapu Jagadeesh Babu Nanubolu Bala Bhaskar Nishant Jain Sreekanth Sivan Vijjulatha Manga 《Bioorganic & medicinal chemistry letters》2017,27(4):792-796
A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, 1H NMR, 13C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI50 values ranging from 0.010 to 0.097 μM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of β-tubulin. 相似文献
144.
Genes essential for the production of a linear, bacterial (1-->3)-beta-
glucan, curdlan, have been cloned for the first time from Agrobacterium sp.
ATCC31749. The genes occurred in two, nonoverlapping, genomic fragments
that complemented different sets of curdlan( crd )-deficient
transposon-insertion mutations. These were detected as colonies that failed
to stain with aniline blue, a (1-->3)-beta-glucan specific dye. One
fragment carried a biosynthetic gene cluster (locus I) containing the
putative curdlan synthase gene, crdS, and at least two other crd genes. The
second fragment may contain only a single crd gene (locus II).
Determination of the DNA sequence adjacent to several locus I mutations
revealed homology to known sequences only in the cases of crdS mutations.
Complete sequencing of the 1623 bp crdS gene revealed highest similarities
between the predicted CrdS protein (540 amino acids) and glycosyl
transferases with repetitive action patterns. These include bacterial
cellulose synthases (and their homologs), which form
(1-->4)-beta-glucans. No similarity was detected with putative
(1-->3)- beta-glucan synthases from yeasts and filamentous fungi.
Whatever the determinants of the linkage specificity of these beta-glucan
synthases might be, these results raise the possibility that
(1-->3)-beta-glucans and (1-->4)-beta-glucans are formed by related
catalytic polypeptides.
相似文献
145.
Un Seng Chio Yumeng Liu SangYoon Chung Woo Jun Shim Sowmya Chandrasekar Shimon Weiss Shu-ou Shan 《The Journal of cell biology》2021,220(11)
The guided entry of tail-anchored protein (GET) pathway, in which the Get3 ATPase delivers an essential class of tail-anchored membrane proteins (TAs) to the Get1/2 receptor at the endoplasmic reticulum, provides a conserved mechanism for TA biogenesis in eukaryotic cells. The membrane-associated events of this pathway remain poorly understood. Here we show that complex assembly between the cytosolic domains (CDs) of Get1 and Get2 strongly enhances the affinity of the individual subunits for Get3•TA, thus enabling efficient capture of the targeting complex. In addition to the known role of Get1CD in remodeling Get3 conformation, two molecular recognition features (MoRFs) in Get2CD induce Get3 opening, and both subunits are required for optimal TA release from Get3. Mutation of the MoRFs attenuates TA insertion into the ER in vivo. Our results demonstrate extensive cooperation between the Get1/2 receptor subunits in the capture and remodeling of the targeting complex, and emphasize the role of MoRFs in receptor function during membrane protein biogenesis. 相似文献
146.
Sowmya Ramesh Karthikeyan Rajagopal Dhanesh Vaikkath Prabha D. Nair Vrisha Madhuri 《Biotechnology letters》2014,36(5):1107-1111
Two encapsulation techniques for rabbit chondrocytes in chitosan/hyaluronic acid gel have been compared. The standard technique involves the cross-linking of chitosan and hyaluronic acid at 2:1 (w/w). In the modified technique, cells were initially added to 33 % of hyaluronic acid dialdehyde and the gelation process was completed with the remaining 67 %. This minimised the cell loss and improved the encapsulation of the cells. By the third week, the modified technique showed better seeding density, with matrix synthesis (per scaffold) of 11 μg as compared to 1.1 μg in the current technique. Relative expression of collagen II with the current technique and the modified technique were 6.4 % and ~1,600 % respectively. The modified technique was superior for matrix synthesis and maintenance of phenotype. 相似文献
147.
M Kale R Ramsey-Goldman S Bernatsky MB Urowitz D Gladman PR Fortin M Petri E Yelin S Manzi S Edworthy O Nived S-C Bae D Isenberg A Rahman JG Hanly C Gordon S Jacobsen E Ginzler DJ Wallace GS Alarcón MA Dooley L Gottesman K Steinsson A Zoma J-L Senécal S Barr G Sturfelt L Dreyer L Criswell J Sibley JL Lee AE Clarke 《Arthritis research & therapy》2012,14(Z3):A15
148.
Isozyme electrophoresis was used to assess possible cospeciation of
parasites (cestodes of the Progamotaenia festiva complex) and their hosts
(Australian diprotodont marsupials) and to compare the extent of
interspecific genetic diversity of the parasites and their hosts. On the
basis of morphology, there are three species in the complex, although
electrophoresis revealed 14 distinct genetic types, most of which were host
specific, although there were three cases of apparent host switching. The
evolutionary relationships among the parasites were only partially
concordant with those among the hosts. Moreover, the extent of
electrophoretic diversity among the parasites was much higher than that
among hosts.
相似文献
149.
Collagenase-3 (matrix metalloproteinase-13) is a metalloproteinase (MMP) that is associated with bone lesions and exhibits variable expression patterns in odontogenic cysts; it may play a role in regulating focal proliferation and maturation of jaw cyst epithelium. We studied the localization, staining intensity and distribution of collagenase-3 in 13 periapical granulomas with epithelium, 16 periapical granulomas without epithelium and 10 radicular cysts using archived formalin fixed, paraffin embedded tissues. A monoclonal antibody against human collagenase-3 was used to evaluate its expression. Immunohistochemical staining intensities of collagenase-3 in all periapical lesions were (?), 4 (10%); (+), 1 (3%); (++), 22 (56%) and (+++), 12 (31%); differences were not statistically significant. Immunohistochemical distribution of collagenase-3 in epithelial cells was (?), 17 (44%); (+), 17 (44%); (++), 5 (13%); in fibroblasts it was (?), 8 (20%); (+), 23 (59%); (++), 8 (21%); in plasma cells it was (?), 7 (18%); (+), 22 (56%); (++), 10 (26%); in macrophages it was (?), 7 (18%); (+), and 15 (38%); and (++), 17 (44%). Statistically significant differences were found in epithelial cells (p = 0.00) and fibroblasts (p = 0.02), whereas differences were not statistically significant for plasma cells and macrophages. Collagenase-3 may play a role in the conversion of a periapical granuloma with epithelium to radicular cyst. MMP's influence not only epithelial rest cell migration, but also invasion of various stromal cells into granulomatous tissue. 相似文献
150.
Sowmya Pattabhi Jacqueline Whittle Raodoh Mohamath Sayda El-Safi Garner G. Moulton Jeffrey A. Guderian Danny Colombara Asem O. Abdoon Maowia M. Mukhtar Dinesh Mondal Javan Esfandiari Shailendra Kumar Peter Chun Steven G. Reed Ajay Bhatia 《PLoS neglected tropical diseases》2010,4(9)