Necroptosis refers to a regulated form of cell death induced by a variety of stimuli. Although it has been implicated in the pathogenesis of many diseases, there is evidence to support that ...necroptosis is not purely a detrimental process. We propose that necroptosis is a "double-edged sword" in terms of physiology and pathology. On the one hand, necroptosis can trigger an uncontrolled inflammatory cascade response, resulting in severe tissue injury, disease chronicity, and even tumor progression. On the other hand, necroptosis functions as a host defense mechanism, exerting antipathogenic and antitumor effects through its powerful pro-inflammatory properties. Moreover, necroptosis plays an important role during both development and regeneration. Misestimation of the multifaceted features of necroptosis may influence the development of therapeutic approaches targeting necroptosis. In this review, we summarize current knowledge of the pathways involved in necroptosis as well as five important steps that determine its occurrence. The dual role of necroptosis in a variety of physiological and pathological conditions is also highlighted. Future studies and the development of therapeutic strategies targeting necroptosis should fully consider the complicated properties of this type of regulated cell death.
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The ...NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes. Diacylglycerol (DAG) at the Golgi rapidly increases, recruiting protein kinase D (PKD), a key effector of DAG. Upon PKD inactivation, self-oligomerized NLRP3 is retained at MAMs adjacent to Golgi, blocking assembly of the active inflammasome. Importantly, phosphorylation of NLRP3 by PKD at the Golgi is sufficient to release NLRP3 from MAMs, resulting in assembly of the active inflammasome. Moreover, PKD inhibition prevents inflammasome autoactivation in peripheral blood mononuclear cells from patients carrying NLRP3 mutations. Hence, Golgi-mediated PKD signaling is required and sufficient for NLRP3 inflammasome activation.
In this study, the effect of packing density, oil type and temperature on the sorption kinetics behavior of cattail fiber was investigated based on Washburn theory by capillary rise test. It was ...found that higher packing density resulted in lower oil sorption capacity due to the less available space among fibers. The sorption coefficient to different oils which represented the sorption rate exhibited large difference with various packing densities. The results illustrated that when the packing density was 0.04 g/cm
3
, the cattail fiber showed higher oil sorption capacity and faster oil sorption rate. With regards to the temperature, results revealed that at the packing density of 0.06 g/cm
3
, the oil sorption capacity of cattail fiber showed little difference when the temperature ranged from 20 to 80 °C. However, the sorption coefficient depicted almost linear enhancement when higher temperature was applied. Moreover, the wetting characteristics of single cattail fiber to three test oils were performed by drop-on-fiber test. It was concluded that three test oils all displayed barrel-shaped droplets on single fiber with the smallest size for diesel oil and the largest for engine oil. Oil drops of vegetable oil and engine oil on single cattail fiber presented a dynamic flow process where smaller droplets converge into large ones. The unique wetting characteristic of cattail fiber was supposed to result from the open-cavity surface structure of cattail fiber.
Sepsis is a systemic inflammatory disease causing life-threatening multi-organ dysfunction. Accumulating evidences suggest that two forms of programmed necrosis, necroptosis and pyroptosis triggered ...by the pathogen component lipopolysaccharide (LPS) and inflammatory cytokines, play important roles in the development of bacterial sepsis-induced shock and tissue injury. Sepsis-induced shock and tissue injury required receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) phosphorylation, caspase11 activation and gasdermin D (GSDMD) cleavage. However, the synergistic effect of necroptosis and pyroptosis in the pathological progress of sepsis remains elusive. In this study, we found that blockage of both necroptosis and pyroptosis (double deletion of Ripk3/Gsdmd or Mlkl/Gsdmd) resulted in accumulative protection against septic shock, systemic blood clotting and multi-organ injury in mice. Bone marrow transplantation confirmed that necroptosis and pyroptosis in both myeloid and nonmyeloid cells are indispensable in the progression of sepsis-induced multi-organ injury. Both RIPK3 and GSDMD signaling collaborated to amplify necroinflammation and tissue factor release in macrophages and endothelial cells, which led to tissue injury. Furthermore, cell death induced by inflammatory cytokines and high-mobility group box 1 could be prevented by double ablation of Ripk3/Gsdmd or Mlkl/Gsdmd, suggesting that a positive feedback loop interconnecting RIPK3/MLKL and GSDMD machinery and inflammation facilitated sepsis progression. Collectively, our findings demonstrated that RIPK3-mediated necroptosis and GSDMD-mediated pyroptosis collaborated to amply inflammatory signaling and enhance tissue injury in the process of sepsis, which may shed new light on two potential targets of combined therapeutic interventions for this highly lethal disorder.
Renal tubular cell (RTC) death and inflammation contribute to the progression of obstructive nephropathy, but its underlying mechanisms have not been fully elucidated. Here, we showed that Gasdermin ...E (GSDME) expression level and GSDME-N domain generation determined the RTC fate response to TNFα under the condition of oxygen-glucose-serum deprivation. Deletion of Caspase-3 (Casp3) or Gsdme alleviated renal tubule damage and inflammation and finally prevented the development of hydronephrosis and kidney fibrosis after ureteral obstruction. Using bone marrow transplantation and cell type-specific Casp3 knockout mice, we demonstrated that Casp3/GSDME-mediated pyroptosis in renal parenchymal cells, but not in hematopoietic cells, played predominant roles in this process. We further showed that HMGB1 released from pyroptotic RTCs amplified inflammatory responses, which critically contributed to renal fibrogenesis. Specific deletion of Hmgb1 in RTCs alleviated caspase11 and IL-1β activation in macrophages. Collectively, our results uncovered that TNFα/Casp3/GSDME-mediated pyroptosis is responsible for the initiation of ureteral obstruction-induced renal tubule injury, which subsequentially contributes to the late-stage progression of hydronephrosis, inflammation, and fibrosis. This novel mechanism will provide valuable therapeutic insights for the treatment of obstructive nephropathy.
A continuous fixed bed study was carried out by using rice husk as a biosorbent for the removal of congo red (CR) from aqueous solution. The effects of important factors, such as the value of initial ...pH, existing salt, the flow rate, the influent concentration of CR and bed depth, were studied. Data confirmed that the breakthrough curves were dependent on flow rate, initial dye concentration and bed depth. Thomas, Adams–Bohart, and Yoon–Nelson models were applied to experimental data to predict the breakthrough curves using non-linear regression and to determine the characteristic parameters of the column useful for process design, while bed depth/service time analysis (BDST) model was used to express the effect of bed depth on breakthrough curves. The results showed that Thomas model was found suitable for the normal description of breakthrough curve at the experimental condition, while Adams–Bohart model was only for a initial part of dynamic behavior of the rice husk column. The data were in good agreement with BDST model. It was concluded that the rice husk column can remove CR from solution.
OBJECTIVEA two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal impact of celiac disease on the risk of chronic kidney disease (CKD).METHODSThe study comprised data ...from three genome-wide association studies involving individuals of European ancestry. The study groups included participants with celiac disease (n = 24,269), CKD (n = 117,165), and estimated glomerular filtration rate levels based on serum creatinine (eGFRcrea, n = 133,413). We employed four widely recognized causal inference algorithms: MR-Egger, inverse variance weighted (IVW), weighted median, and weighted mode. To address potential issues related to pleiotropy and overall effects, MR-Egger regression and the MR-PRESSO global test were performed. Heterogeneity was assessed using Cochran's Q test.RESULTSWe identified 14 genetic variants with genome-wide significance. The MR analysis provided consistent evidence across the various methodologies, supporting a causal relationship between celiac disease and an elevated risk of CKD (odds ratio (OR)IVW = 1.027, p = 0.025; ORweighted median = 1.028, P = 0.049; ORweighted mode = 1.030, p = 0.044). Furthermore, we observed a causal link between celiac disease and a decreased eGFRcrea (ORIVW = 0.997, P = 2.94E-06; ORweighted median = 0.996, P = 1.68E-05; ORweighted mode = 0.996, P = 3.11E-04; ORMR Egger = 0.996, P = 5.00E-03). We found no significant evidence of horizontal pleiotropy, heterogeneity, or bias based on MR-Egger regression, MR-PRESSO, and Cochran's Q test.CONCLUSIONThe results of this study indicate a causal relationship between celiac disease and an increased risk of CKD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this study, kapok fiber powder (KFP) was evaluated as a wicking material for the application of mechanical lubricants. KFP had lengths ranging from several microns to 2 mm, with part of the hollow ...lumen being compressed. Experiments showed that the oil sorption capacity of KFP for mineral oil and PAO4 was 21.9 g/g, and 19.9 g/g, respectively. The oil release behavior of oil-impregnated KFP was quantitatively evaluated by a device proposed in the present study to simulate the usage of lubricant in bearings. The results indicated a two-step oil release process including a rapid release phase and a slow release phase. The cumulative oil release increased with an increasing oil/fiber ratio and temperature. The release mechanism of oil-impregnated KFP was further investigated by release kinetics models which demonstrated that the oil release followed Fickian diffusion and could be described by the Rigter–Peppas model. These results are proposed to provide a reference for the evaluation of the oil release performance of oil-impregnated wicking materials when they are applied in mechanical bearing field.
A new composite adsorbent, iron oxide coated zeolite (IOCZ), was characterized and employed for the removal of Cu(II) from aqueous solution using fixed bed column. Scanning electron microscope (SEM), ...FTIR, X-ray diffraction spectrum (XRD) and BET analyses were used to study the surface properties of the coated layer. The effects of various experimental conditions, such as the flow rate, initial metal concentration and bed depth, were studied. The dynamics of the adsorption process were fitted by Adams–Bohart model and Thomas model. The Thomas model was found suitable for the description of breakthrough curve at all experimental conditions, while Adams–Bohart model was only for an initial part of dynamic behavior of the IOCZ column. The bed depth service time (BDST) model was applied to predict the service times with other flow rate and initial concentration. The theoretical breakthrough curve was compared with experimental breakthrough curve profile in the dynamic process. The saturated column was regenerated by 1
mol
l
−1 hydrogen chloride solution and IOCZ could be reused in Cu(II) removal.
Oil spills have become a global concern due to their environmental and economic impact. Various methods, including the use of fibers as sorbents, have been developed for oil spill concern. Poplar ...seed fiber is a plant biomass that has the potential of being used as low-cost sorbent. In this study, the physicochemical and sorption characteristics of poplar seed fiber as an oil sorbent was evaluated. Fourier transform infrared and scanning electron microscopy analyses showed that poplar seed fiber was a lignocellulosic material with smooth surface and hollow lumen. Oil sorption tests showed that loose poplar seed fibers could absorb 53.74 g/g of diesel oil, 65.85 g/g of motor oil and 67.97 g/g of vegetable oil, which were higher than that of kapok and cotton fiber. The availability of void fraction inside the fiber assembly coupled with hollow fiber structure and hydrophobicity/oleophilicity of poplar seed fiber were the main contributing factors. Moreover, the oil sorption kinetics of poplar seed fiber, including the effect of packing density of fiber assembly, oil types on sorption capacity and rate, was analyzed by a wicking method. Results illustrated that the oil sorption capacity was closely related to the packing density of fiber assembly, with an apparent decrease when the packing density changed from 0.05 g/cm3 to 0.09 g/cm3. For sorption rate, the highest oil sorption coefficients were observed for diesel oil, of 0.36 g2/s, 0.32 g2/s and 0.30 g2/s at the packing densities of 0.05 g/cm3, 0.07 g/cm3 and 0.09 g/cm3, respectively, which were about 10 times higher than that of vegetable oil and 70 times higher than that of motor oil.
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