THE IMMUNOTHERAPEUTIC EFFECT OF IL-22 VERSUS PRAZIQUANTEL TREATMENT AGAINST S.MANSONI –INDUCED LIVER FIBROSIS IN MICE

Background/Aim:Praziquantel (PZQ), the primary medication for schistosomiasis treatment, exhibits a potential resistance by the parasite. Therefore, the development of a new effective treatment is obligated. Interleukin-22 (IL-22) has been reported to have a hepatoprotective effect. The current study aimed to compare the effectiveness of IL-22 treatment versus PZQ against S. mansoni - induced liver fibrosis in mice. Materials and Methods: Forty male albino mice were divided into control, infected, IL-22 (0.36 µg/kg),  and PZQ (a single dose of 600 mg/kg) groups. PZQ was administered alone or in combination with IL-22. Inflammatory indicators [tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-22, and immunoglobulin E (IgE)], hepatic expressions of signal transducer and activator of transcription 3 (STAT3), β-catenin, and miR let-7a gene expressions, and liver granuloma index (GI) were estimated. Results:The present result revealed a significant (P <0.05) reduction in liver GI and the pro-inflammatory cytokine, TNF-α, after the treatment with IL-22. Moreover, the treatment enhanced significantly (P <0.05) let-7a miRNA and STAT3 gene expressions as well as downregulated (P <0.05) β-catenin mRNA, which in turn could reduce fibrosis resulting from S. mansoni infection. On the other hand, PZQ treatment alone or in combination with IL-22 reduced significantly (P <0.05) proinflammatory cytokines and IgE but failed to decrease GI or β-catenin gene expression, which might cause a negative impact on liver fibrosis.  Conclusion:IL-22 could be a potential immunotherapeutic agent for S.mansoni-induced liver fibrosis, compared to PZQ, through activating STAT3 and let-7a downstream signalling pathways and inhibiting β-catenin pathway

Optimization methodology for high COD nutrient-limited wastewaters treatment using BAS process

Optimization of biofilm activated sludge (BAS) process via mathematical modelling is an entangle activity since economic, environmental objective and technical decision must be considered. This paper presents a methodology to optimize the operational conditions of BAS process in four steps by combining dynamic simulation techniques with non-linear optimization methods and with operative decision-making criteria. Two set of variables are separately prioritized in the methodology: essential variables related to physical operation to enforce established process performance, and refinement variables related to biological processes that can generate risks of bulking, pin-point floc and rising sludge. The proposed optimization strategy is applied for the treatment of high COD wastewater under nutrient limitation using an integrated mathematical model for COD removal that include predation, hydrolysis and a simplified approach to the limiting solids flux theory in the secondary clarifier in order to facilitate the convergence of the optimization solver. The methodology is implemented in a full-scale wastewater treatment plant for a cellulose and viscose fibre mill obtaining (i) improvement of the effluent quality index (Kg pollution/m3) up to 62% and, (ii) decrease the operating cost index (€/m3) of the process up to 30% respect the regular working operational conditions of the plant. The proposed procedure can be also applied to other biological treatments treating high COD nutrient-limited industrial wastewater such as from textile and winery production among others

Effect of the Material Parameters on Layered Viscoelastic Frictional Contact Systems

In the design process, one of the main targets is to reduce the peak values of the contact stresses. This can be attained by layering the contacting bodies by layers of different material characteristics. Viscoelastic materials are characterized by either a stress relaxation or a creep deformation; therefore, the contacting bodies can be layered with such materials to attain this target. This paper discusses effects of the material characteristics of viscoelastic layers upon the unbounded contact configuration. Three material parameters are considered: the layer/contact solids stiffness ratio, the delayed/instantaneous elasticity ratio, and the material relaxation time. The results are obtained by using a two-dimensional time-dependent nonlinear computational model, developed by the authors, capable of analyzing quasistatic viscoelastic frictional contact problems

Targeting Autophagy, Apoptosis, and SIRT1/Nrf2 Axis with Topiramate Underlies Its Neuroprotective Effect against Cadmium-Evoked Cognitive Deficits in Rats

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington’s disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aβ42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3β and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits