Lung tissue extracellular matrix-derived hydrogels protect against radiation-induced lung injury by suppressing epithelial–mesenchymal transition

This study aimed to examine whether lung tissue extracellular matrix (ECM) hydrogels have protective effects on radiation-induced lung injury (RILI). The cytocompatibility and histocompatibility were tested for the obtained ECM-derived hydrogel. Sprague–Dawley rats were randomly divided into three groups (n = 18): control group (control); rats receiving irradiation and intratracheal injection of normal saline (IR + NS); and rats receiving irradiation and intratracheal injection of lung ECM-derived hydrogel (IR + ECM). The wet/dry weight ratio was used to evaluate the congestion and edema of the lungs. Histopathological analysis of lung tissues was performed using hemotoxylin and eosin staining and Masson's trichrome staining. Immunohistochemical staining and western blot analyses were carried out to determine the expression of epithelial–mesenchymal transition (EMT)-related proteins in lung tissues (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin). In addition, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6), hydroxyproline, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were also evaluated. The ECM-derived hydrogels had good cytocompatibility and histocompatibility. ECM-derived hydrogel treatment improved lung histopathology injury and pulmonary edema. Higher expression of E-cadherin and lower expression of vimentin and α-SMA were found in the IR + ECM group compared with those in the IR + NS group. Hydroxyproline levels were reduced by ECM-derived hydrogel treatment compared with those in the IR + NS group. Obvious increases of TNF-α, IL-6, and TGF-β1 were identified following irradiation. Marked reductions in MDA content and increases in SOD were induced by ECM-derived hydrogel treatment in rats after radiation. ECM-derived hydrogels were shown to protect against RILI, potentially by reducing EMT, inflammation, and oxidative damage.     

Biocides formulation of essential oils having antimicrobial activity

Essential oils of fennel, peppermint, caraway, eucalyptus, geranium and lemon were tested for their antimicrobial activities against some plant pathogenic micro-organisms (Fusarium oxysporum, Alternaria alternate, Penicilium italicum Penicilium digitatum and Botyritus cinerea). Essential oils of fennel, peppermint, caraway were selected as an active ingredient for the formulation of biocides due to their efficiency in controlling the tested micro-organisms. Successful emulsifiable concentrates (biocides) were prepared from these oils using different emulsifiers (Emulgator B.L.M. Tween20 and Tween80) and different fixed oils (sesame, olive, cotton and soybean oils). Physico-chemical properties of the formulated biocide (spontaneous emulsification, emulsion stability test, cold stability and heat stability tests as well as viscosity, surface tension and pH) were measured. The prepared biocides were ready to be tested for application in a future work as a safe pesticide against different pathogens.     

Molecular characterization and antigenic properties of a novel Babesia gibsoni glutamic acid-rich protein (BgGARP)

Identification and molecular characterization of Babesia gibsoni proteins with potential antigenic properties are crucial for the development and validation of the serodiagnostic method. In this study, we isolated a cDNA clone encoding a novel B. gibsoni 76-kDa protein by immunoscreening of the parasite cDNA library. Computer analysis revealed that the protein presents a glutamic acid-rich region in the C-terminal. Therefore, the protein was designated as B. gibsoni glutamic acid-rich protein (BgGARP). A BLASTp analysis of a translated BgGARP polypeptide demonstrated that the peptide shared a significant homology with a 200-kDa protein of Babesia bigemina and Babesia bovis. A truncated BgGARP cDNA (BgGARPt) encoding a predicted 13-kDa peptide was expressed in Escherichia coli (E. coli), and mouse antisera against the recombinant protein were used to characterize a corresponding native protein. The antiserum against recombinant BgGARPt (rBgGARPt) recognized a 140-kDa protein in the lysate of infected erythrocytes, which was detectable in the cytoplasm of the parasites by confocal microscopic observation. In addition, the specificity and sensitivity of enzyme-linked immunosorbent assay (ELISA) with rBgGARPt were evaluated using B. gibsoni-infected dog sera and specific pathogen-free (SPF) dog sera. Moreover, 107 serum samples from dogs clinically diagnosed with babesiosis were examined using ELISA with rBgGARPt. The results showed that 86 (80.4%) samples were positive by rBgGARPt-ELISA, which was comparable to IFAT and PCR as reference test. Taken together, these results demonstrate that BgGARP is a suitable serodiagnostic antigen for detecting antibodies against B. gibsoni in dogs.     

Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via Nanostructured Lipid Carrier (NLC) Formulation

Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but unfortunately with poor bioavailability. Aiming to improve its poor oral bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by high-speed homogenization followed by ultrasonication and evaluated in vitro. Bioavailability and pharmacodynamic studies were also performed. The resultant NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system which consequently produced larger particle size and polydispersity index, smaller zeta potential values, and lower short-term (30 days) physical stability than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6?±?5% and 96.2?±?1.6%. TQ AUC_0–t values were higher in animals treated with NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12, respectively) higher than TQ suspension, indicating bioavailability enhancement by NLC formulation. Hepatoprotective effects of F12 showed significant (P?<?0.05) decrease in both serum alanine amino transferase and aspartate amino transferase to reach 305.0?±?24.88 and 304.7?±?23.55 U/ml, respectively, when compared with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P?<?0.05) decline of malondialdehyde and elevation of reduced glutatione. This improvement was also confirmed histopathologically.     

Speeding up Monte Carlo molecular simulation by a non-conservative early rejection scheme

Monte Carlo (MC) molecular simulation describes fluid systems with rich information, and it is capable of predicting many fluid properties of engineering interest. In general, it is more accurate and representative than equations of state. On the other hand, it requires much more computational effort and simulation time. For that purpose, several techniques have been developed in order to speed up MC molecular simulations while preserving their precision. In particular, early rejection schemes are capable of reducing computational cost by reaching the rejection decision for the undesired MC trials at an earlier stage in comparison to the conventional scheme. In a recent work, we have introduced a ‘conservative’ early rejection scheme as a method to accelerate MC simulations while producing exactly the same results as the conventional algorithm. In this paper, we introduce a ‘non-conservative’ early rejection scheme, which is much faster than the conservative scheme, yet it preserves the precision of the method. The proposed scheme is tested for systems of structureless Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. Numerical experiments were conducted at several thermodynamic conditions for different number of particles. Results show that at certain thermodynamic conditions, the non-conservative method is capable of doubling the speed of the MC molecular simulations in both canonical and NVT-Gibbs ensembles.     

Using phylogeographic approaches to analyse the dispersal history,velocity and direction of viral lineages — Application to rabies virus spread in Iran

Recent years have seen the extensive use of phylogeographic approaches to unveil the dispersal history of virus epidemics. Spatially explicit reconstructions of viral spread represent valuable sources of lineage movement data that can be exploited to investigate the impact of underlying environmental layers on the dispersal of pathogens. Here, we performed phylogeographic inference and applied different post hoc approaches to analyse a new and comprehensive data set of viral genomes to elucidate the dispersal history and dynamics of rabies virus (RABV) in Iran, which have remained largely unknown. We first analysed the association between environmental factors and variations in dispersal velocity among lineages. Second, we present, test and apply a new approach to study the link between environmental conditions and the dispersal direction of lineages. The statistical performance (power of detection, false‐positive rate) of this new method was assessed using simulations. We performed phylogeographic analyses of RABV genomes, allowing us to describe the large diversity of RABV in Iran and to confirm the cocirculation of several clades in the country. Overall, we estimate a relatively high lineage dispersal velocity, similar to previous estimates for dog rabies virus spread in northern Africa. Finally, we highlight a tendency for RABV lineages to spread in accessible areas associated with high human population density. Our analytical workflow illustrates how phylogeographic approaches can be used to investigate the impact of environmental factors on several aspects of viral dispersal dynamics.     

Extracellular hemoglobin combined with an O2-generating material overcomes O2 limitation in the bioartificial pancreas

The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O₂ supply after transplantation remains a major challenge. In this study, we address the O₂ limitation by combining silicone-encapsulated CaO₂ (silicone-CaO₂) to generate O₂ with an extracellular hemoglobin O₂-carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O₂-diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O₂ species produced by silicone-CaO₂. While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO₂ alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO₂ alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O₂ provider with hemoglobin as an effective strategy to overcome O₂ limitations in tissue engineering.     

Biogas manufacture from co-digestion of untreated primary sludge with raw chicken manure under anaerobic mesophilic environmental conditions

This work aimed to co-digest various wastes to assess the best combination of all mixing ratio, also at choosing the best ratio between untreated primary sludge (UPS) singly from two sources, (South valley University (SUPS) and Abu tesht wastewater station (AUPS) and raw chicken manure (RCM) and comparing the results in either case. The co-digestions of untreated primary sludge from Abu tesht wastewater treatment stations with different levels of raw chicken manure (0:100, 10:90, 30:70, 50:50, 90:10, and 100:0) to obtain the best mixtures. Also, co-digestion of untreated primary sludge from south valley university with different levels of raw chicken manure at the same ratios, to obtain the best mixtures. Batch digestion tests were applied in 2.5 L digester with a working volume of 2.0 L. The samples in triplicates were separately loaded into the digesters locally fabricated and kept for 20 days as a retention period and diluted with the same amount of water. Mesophilic under 35 °C was adopted for untreated primary sludge as well as mixtures with raw chicken manure based on total solids (TS) and volatile solid (VS) proportions. The average biogas yields from AUPS/RCM mixture obtained ranged from 8570 to 5600 ml, by the following descending order, 10: 90 > 90:10 and so on >100:0, and the average biogas yields from SUPS/RCM obtained ranged from 6330 to 5635 ml, in the order of 90: 10 > 10:90 and so on >100:0. The results showed highest biogas yield from AUPS/RCM and SUPS/RCM mixtures with mixing ratio of 10:90 and 90:10, respectively, however, the lowest biogas production detected in separate digestion of AUPS and SUPS. The results indicated that co-digestion between the sludge and raw chicken manure could increase total biogas production volume, enhance sludge treatment process, and produce eco-friendly sludge because of co-digestion process than separate processing of each feedstock.     

The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo

The CD134-CD134 ligand (CD134L) costimulatory pathway has been shown to be critical for both T and B cell activation; however, its role in regulating the alloimmune response remains unexplored. Furthermore, its interactions with other costimulatory pathways and immunosuppressive agents are unclear. We investigated the effect of CD134-CD134L pathway blockade on allograft rejection in fully MHC-mismatched rat cardiac and skin transplantation models. CD134L blockade alone did not prolong graft survival compared with that of untreated recipients, and in combination with donor-specific transfusion, cyclosporine, or rapamycin, was less effective than B7 blockade in prolonging allograft survival. However, in combination with B7 blockade, long-term allograft survival was achieved in all recipients (>200 days). Moreover, this was synergistic in reducing the frequency of IFN-gamma-producing alloreactive lymphocytes and inhibiting the generation of activated/effector lymphocytes. Most impressively, this combination prevented rejection in a presensitized model using adoptive transfer of primed lymphocytes into athymic heart transplant recipients. In comparison to untreated recipients (mean survival time (MST): 5.3 +/- 0.5 days), anti-CD134L mAb alone modestly prolonged allograft survival (MST: 14 +/- 2.8 days) as did CTLA4Ig (MST: 21.5 +/- 1.7 days), but all grafts were rejected within 24 days. Importantly, combined blockade further and significantly prolonged allograft survival (MST: 75.3 +/- 12.7 days) and prevented the expansion and/or persistence of primed/effector alloreactive T cells. Our data suggest that CD134-CD134L is a critical pathway in alloimmune responses, especially recall/primed responses, and is synergistic with CD28-B7 in mediating T cell effector responses during allograft rejection. Understanding the mechanisms of collaboration between these different pathways is important for the development of novel strategies to promote long-term allograft survival.