High-throughput sequencing was applied to compare the intestinal microbiota in largemouth bronze gudgeon either healthy or affected by furunculosis. Proteobacteria, Actinobacteria, Tenericutes, Firmicutes and Bacteroidetes were detected as the predominant bacterial phyla in the gut of both diseased and healthy fish. The abundance of Proteobacteria differed significantly between the two groups of fish, mainly due to the overwhelming prevalence of Aeromonas in the diseased fish (81% ± 17%), while the genus was unevenly spread among the apparently healthy fish (33% ± 33%). The bacterial diversity in the intestine of diseased fish was markedly lower than in healthy fish. Analysis revealed the significant dissimilarity between the gut microbiota of diseased and healthy fish. The bacterial profiles in the gut were further characterized with the 28 phylotypes that were shared by the two groups. In diseased fish, two shared OTUs (OTU0001 and OTU0013) were closely related to Aeromonas salmonicida, their total proportion exceeding 70% of the sequences in diseased fish, while averaging 5.2% ± 4.6% in the healthy fish. This result suggested the presence of healthy carriers of pathogenic A. salmonicida among the farmed fish, and the gut appeared as a probable infection source for furunculosis in largemouth bronze gudgeon.
IntroductionImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4.MethodsClinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed.ResultsThe first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased.ConclusionsProminent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.
Regulation of integrin activation occurs by specific interactions among cytoplasmic proteins and integrin ␣ and  cytoplasmic tails. We report that the catalytic subunit of protein phosphatase 1 (PP1c) constitutively associates with the prototypic integrin ␣ IIb  3 in platelets and in cell lines overexpressing the integrin. PP1c binds directly to the cytoplasmic domain of integrin ␣ IIb subunit containing a conserved PP1c binding motif 989 KVGF 992 . Anchored PP1c is inactive, while thrombininduced platelet aggregation or fibrinogen-␣ IIb  3 engagement caused PP1c dissociation and concomitant activation as revealed by dephosphorylation of PP1c substrate, myosin light chain. Inhibition of ligand binding to activated ␣ IIb  3 blocks PP1c dissociation and represses PP1c activation. These studies reveal a previously unrecognized role for integrins whereby the ␣ subunit cytoplasmic tail localizes the machinery for initiating and temporally maintaining the regulatory signaling activity of a phosphatase.Integrin signaling mediated by reversible phosphorylation of proteins controls fundamental cellular processes like adhesion and migration. The prototypic integrin, platelet ␣ IIb  3 , undergoes affinity/avidity modulation for its ligands through the process of inside-out signaling, resulting in firm adhesion and platelet aggregation upon vascular injury. Subsequent binding of fibrinogen to integrin ␣ IIb  3 generates outside-in signaling (1). Both ␣ IIb  3 inside-out and outside-in signaling result in tyrosine or serine/threonine phosphorylation of multiple signaling proteins, serving to initiate and amplify signaling cascades that support the formation of stable platelet-platelet and platelet-extracellular matrix interactions. Cytoskeletal proteins like talin (2), and non-receptor tyrosine and serine/threonine kinases, including Src, Csk, Syk (3), protein kinase C (4), integrin-linked kinase (5), and calcium-and integrin-binding protein (6), associate with integrin  and ␣ cytoplasmic tails and mediate these integrin-dependent signaling events.The net tyrosine or serine/threonine phosphorylation of a protein substrate is regulated by the activities of both protein kinases and phosphatases. While kinases and phosphorylation events during integrin mediated signaling have been clearly demonstrated, the role for phosphatases is poorly understood. Phosphatases play an essential role in dampening platelet phosphorylation events, and serine/threonine dephosphorylation of cytoskeletal proteins like cofilin, talin, and vasodilatorstimulated phosphoprotein correlates with platelet activation (7-9). Unlike the situation with kinases, only serine/threonine protein phosphatase PP2A has been reported to associate with integrin  1 (10), while only tyrosine phosphatase SHP-2 is known to associate with  3 (11). We are unaware of any reports of a phosphatase associating with an integrin ␣ subunit.PP1 is the best characterized and major serine/threonine protein phosphatase. The catalytic subunit of PP1 1 (PP1c) does not exist f...
Background: Osteoporosis is a chronic bone metabolism disorder affecting millions of the world population. The RANKL/RANK/OPG signaling pathway has been confirmed to be the main regulator of osteoporosis. It is of great interest to identify appropriate therapeutic agents that can regulate the RANKL/RANK/OPG pathway. Baicalin (BA) is a well-known traditional Chinese medicine formula against various inflammatory diseases with a proven role of the RANKL/RANK/OPG pathway regulation. However, the potential effect of BA on osteoporosis and the mechanisms underlying this remain unclear. In the present study, we aimed to evaluate the efficacy of BA in the prevention of dexamethasone (DEX)-induced osteoporosis in zebrafish. Methods: In this study, growth and development changes of zebrafish and calcein staining were assessed with a micrograph. The expression levels of RANKL and OPG and transcription factors in response to DEX induction and BA administration were evaluated by Western blotting and qRT-PCR. In addition, the intermolecular interactions of BA and RANKL were investigated by molecular docking. Results: Results show that BA enhances the growth and development of dexamethasone (DEX)-induced osteoporosis in zebrafish larvae. Calcein staining and calcium and phosphorus determination revealed that BA ameliorates mineralization of DEX-induced osteoporosis zebrafish larvae. BA also regulates the expression of RANKL and OPG and hampers the changes in gene expression related to bone formation and resorption under the induction of DEX in zebrafish. It can be inferred by molecular docking that BA may interact directly with the extracellular domain of RANKL. Conclusion: The findings, herein, reveal that BA ameliorates DEX-induced osteoporosis by regulation of the RANK/RANKL/OPG signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.