The major pathological changes during Schistosoma J. infection are characterized by granulomatous inflammation in the liver, a cellular immune response to schistosomal egg antigens. The molecular mechanisms initiating or promoting this schistosomal granulomatous inflammation remain poorly understood. In the present study, we first demonstrated that in mice infected with Schistosoma J. for 6 weeks exhibited increased levels of IL-1β in liver, a major product of NLRP3 inflammasomes and collagen deposition around the eosinophilic granuloma with Schistosoma J. eggs, which was substantially attenuated by caspase-1 inhibitor, YVAD. This activation of the NLRP3 inflammasome occurred in hepatic stellate cells (HSCs), as shown by a marked increase in co-localization of IL-1β with HSCs marker, desmin. Using isolated, cultured mouse HSCs, we further explored the mechanisms by which soluble egg antigen (SEA) from Schistosoma J. activates NLRP3 inflammasomes. SEA induced the formation and activation of NLRP3 inflammasomes, which was associated with both redox regulation and lysosomal dysfunction, but not with potassium channel activation. These results suggest that NLRP3 inflammasome activation in HSCs may serve as an early mechanism to turn on the inflammatory response and thereby instigate liver fibrosis during Schistosoma J. infection.
Postoperative
adhesion is a common complication of abdominal surgery,
which always has many adverse effects in patients. At present, there
is still a lack of effective treatment measures and materials to prevent
adhesion in the clinics. Herein, we report the potential use of J-1-ADP
hydrogel formed by natural antimicrobial peptide jelleine-1 (J-1)
self-assembling in adenosine diphosphate (ADP) sodium solution to
prevent postsurgery adhesion formation. J-1-ADP hydrogel was found
to have good antimicrobial activity against the bacteria and fungi
tested and can be used to prevent tissue infection, which was thought
to be one of the incitements of adhesion. Due to ADP being a platelet-activating
factor, J-1-ADP hydrogel showed significant hemostatic activity in vitro verified by whole blood coagulation, plasma coagulation,
platelet activation, and platelet adhesion assays. Further, it showed
potent hemostatic activity in a mouse liver hemorrhage model. Bleeding
was believed to be a cause of the formation of postsurgery adhesion.
J-1-ADP hydrogel had a significant antiadhesion effect in a rat side
wall defect–cecum abrasion model. In addition, it had good
biocompatibility and degradation properties. So the present study
may provide an alternative strategy for designing antimicrobial peptide
hydrogel material to prevent postoperative adhesion formation in the
clinic.
Most
coalbed methane (CBM) reservoirs contain moisture that can
have an impact on adsorption and diffusion of CBM, so moisture content
is an important factor that affects CBM production. CO2 can be used to improve CBM production on site. Combined with these
two points, regulations of CH4 adsorption and diffusion
are sought under different conditions when CO2 is injected
into coal seams with moisture. Slit pores with different moisture
contents (1%, 2%, 4%, and 6%) and random models are established. Molecular
simulations are carried out, respectively, from 0 MPa to 10 MPa at
293.15, 303.15, and 313.15 K. Relative to CO2, the interaction
of CH4 and −C–C– is weaker, indicating
that CO2 can adsorb more steadily on the surface of coal.
Water molecules preferentially adsorb on the oxygen functional groups,
and then water molecules adsorb each other with hydrogen bonding to
form clusters that can interfere with the adsorption and diffusion
of CO2 and CH4. Because of the influence of
functional groups, hydrogen bonding, and micropore filling, the adsorption
capacity of H2O can increase steeply at very low pressure.
The phenomenon is not beneficial to the CBM exploitation.
Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S. japonicum infection. Furthermore, it is demonstrated that inhibition of NLRP3 inflammasome significantly alleviates the liver inflammation and collagen deposition that are induced by infection with S. japonicum. The mechanism of SEA-induced NLRP3 inflammasome activation is studied in isolated, cultured mouse HSCs and it is shown that SEA-induced NLRP3 inflammasome activation in HSCs is dependent upon the activities of spleen tyrosine kinase (Syk), an enzyme usually associated with a pathogen recognition receptor for fungal pathogens. Moreover, it is demonstrated that Dectin-1 and JNK signaling are also involved in SEA-induced NLRP3 inflammasome activation in HSCs. These data shed new light on the mechanisms of NLRP3 inflammasome activation during an infection with S. japonicum, and further characterize its role in schistosomiasis-associated liver fibrosis (SSLF).
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