Myxoma virus expressing LIGHT (TNFSF14) pre-loaded into adipose-derived mesenchymal stem cells is effective treatment for murine pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a weakly immunogenic fatal neoplasm. Oncolytic viruses with dual anti-cancer properties—oncolytic and immune response-boosting effects—have great potential for PDAC management. Adipose-derived stem cells (ADSCs) of mesenchymal origin were infected ex vivo with recombinant myxoma virus (MYXV), which encodes murine LIGHT, also called tumor necrosis factor ligand superfamily member 14 (TNFSF14). The viability and proliferation of ADSCs were not remarkably decreased (1–2 days) following MYXV infection, in sharp contrast to cells of pancreatic carcinoma lines studied, which were rapidly killed by the infection. Comparison of the intraperitoneal (IP) vs. the intravenous (IV) route of ADSC/MYXV administration revealed more pancreas-targeted distribution of the virus when ADSCs were delivered IP to mice bearing orthotopically injected PDAC. The biodistribution, tumor burden reduction and anti-tumor adaptive immune response were examined. Bioluminescence data, used to assess the presence of the luciferase-tagged virus after IP injection, indicated enhanced trafficking into the pancreata of mice bearing orthotopically-induced PDAC, as compared to tumor-free animals, resulting in extended survival of the treated PDAC-seeded animals and in the boosted expression of key adaptive immune response markers. We conclude that ADSCs pre-loaded with transgene-armed MYXV and administered IP allow for the effective ferrying of the oncolytic virus to sites of PDAC and mediate improved tumor regression

Ozone as a Catalyst of Surplus Activated Sludge Hydrolysis for the Biogas Production Enhancement

The biogas produced in the methane fermentation is valuable due to its use as a renewable energy source. A promising method of biogas production intensification is sludge flocs disintegration via ozonation. The aim of this study was to check the impact of the ozonation on the efficiency and kinetics of biogas production from surplus activated sludge (SAS). Processes were carried out batchwise at 37 °C. The following analyses were performed: pH, alkalinity, dry matter, dry organic matter, chemical oxygen demand, total organic carbon, total nitrogen, elemental analysis (CHNS), the biochemical potential of methane by NIR spectroscopy, and the amount and composition of biogas. The results showed that the ozonation process had no effect on the elemental composition and chemical structure of SAS. The chemical formula of SAS (C2.97H4.68O1.20N0.3) and a simplified equation describing the methane fermentation process were determined. Ozonation caused the hydrolysis of some organic compounds from sludge flocs and increased the efficiency of biogas production. The methane content in biogas was higher by about 2.5%, while the amount of produced biogas rose by up to 21% for the ozonized sludge. The kinetic constants of first-order reaction were between 0.219 and 0.323 d−1, with an upward trend due to ozonation

Ozone as a Catalyst of Surplus Activated Sludge Hydrolysis for the Biogas Production Enhancement

The biogas produced in the methane fermentation is valuable due to its use as a renewable energy source. A promising method of biogas production intensification is sludge flocs disintegration via ozonation. The aim of this study was to check the impact of the ozonation on the efficiency and kinetics of biogas production from surplus activated sludge (SAS). Processes were carried out batchwise at 37 °C. The following analyses were performed: pH, alkalinity, dry matter, dry organic matter, chemical oxygen demand, total organic carbon, total nitrogen, elemental analysis (CHNS), the biochemical potential of methane by NIR spectroscopy, and the amount and composition of biogas. The results showed that the ozonation process had no effect on the elemental composition and chemical structure of SAS. The chemical formula of SAS (C2.97H4.68O1.20N0.3) and a simplified equation describing the methane fermentation process were determined. Ozonation caused the hydrolysis of some organic compounds from sludge flocs and increased the efficiency of biogas production. The methane content in biogas was higher by about 2.5%, while the amount of produced biogas rose by up to 21% for the ozonized sludge. The kinetic constants of first-order reaction were between 0.219 and 0.323 d−1, with an upward trend due to ozonation

Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment

Influence of Inoculum Thermal Pretreatment Time on Hydrogen Production in Dark Fermentation

Dark fermentation (DF) of kitchen waste (KW) is a promising technology for the production of renewable biohydrogen. It can be both a method of obtaining clean energy and a sustainable waste management. Despite its potential, this process requires further research to improve efficiency. The aim of the research was to test the effect of thermal pretreatment of the inoculum on H2 and volatile fatty acids (VFAs) production in the DF process. The process was carried out at 37 °C, in batch mode. The digested sludge from the Group Wastewater Treatment Plant in Lodz was used as inoculum. KW from households was used as substrate. The inoculum was pre-treated at 70 °C for 15 and 30 min. Two control reference experiments were also used. The first without the inoculum, and the second without heating the inoculum. The thermal pretreatment inhibited methane production and increased hydrogen production. After the thermal pretreatment, the amount of CO2 produced during the process decreased compared to the bioreactor without inoculum pretreatment. Additionally, the main VFAs in the samples with pretreated inoculum were acetic and butyric acids, which are associated with hydrogen production in the biochemical pathways of the DF process. However, the time of thermal pretreatment had no significant effect on H2 production

Emission and neutralization of methane from a municipal landfill-parametric analysis

An attempt was made to estimate the annual production ofCH4 at a municipal waste landfill site in Poland. As a matter of fact, the extent of the unorganized emission of CH4 from the landfill surface was approached based on the adopted mathematical model. TheWard agglomeration method for cluster analysis and the Pearson coeffcient were employed to evaluate the distance-based similarity measure and to optimize methods for estimating methane emissions from a landfill as well as to verify the input parameters for the model. In order to calculate the content of biodegradable organic parts in the waste, morphological tests of the landfilled waste were performed. Physical quantities, measurements and the actual amount of the landfilled waste as well as the volume of CH4 neutralized in a collective flare were implemented in the model, respectively. The model-based findings and experimental outcome demonstrated stable gas production in the landfill with a high CH4 content. On the other hand, a rather low effciency of the landfill passive degassing installation indicated the necessity to design and develop its active counterpart with the prospective application of the generated biogas for energy production in a cogeneration system