Search

Several strategies are available for mitigating greenhouse gas (GHG) emissions associated with dairy manure management in barns, storage units, and fields. For instance, incorporation of manure into the soil, solid-liquid separation, composting, enclosed manure storage, and anaerobic digestion have been identified as good options. However, these strategies are not widely adopted in Canada because clear information on their effectiveness to abate the whole-farm GHG footprint is lacking. Better information on the most cost-effective options for reducing on-farm GHG emissions would assist decision making for dairy producers and foster adoption of the most promising approaches on Canadian dairies. In this context, whole-farm modeling provides a tool for evaluating different GHG abatement strategies. An Excel-based linear optimization model (N-CyCLES) was used to assess the economics and the nutrient and GHG footprints of two representative dairy farms in Québec, Canada. The farms were located in regions with contrasting climates (southwestern and eastern Québec). The model was developed to optimize feeding, cropping, and manure handling as a single unit of management, considering the aforementioned mitigation options. Greenhouse gas emissions from the different simulated milk production systems reached 1.27 to 1.85 kg CO2e kg-1 of corrected milk, allowing GHG reductions of up to 25% compared to the base system described in Part I. Solid-liquid separation had the greatest GHG mitigation potential, followed by the digester-like strategy involving a tight cover for gas burning. However, both options implied a decrease in farm net income. Manure incorporation into the soil and composting were associated with high investment relative to their GHG abatement potential. The most cost-effective option was using a loose cover on the manure storage unit. This approach lessened the manure volume and ammonia-N volatilization, thereby reducing fertilizer and manure spreading costs, increasing crop sales and profit, and enhancing the whole-farm N and GHG footprints. Consequently, covering the manure tanks appears to be an economically viable practice for Québec dairy farms. [ABSTRACT FROM AUTHOR]

Tie-stall housing (93%) and solid manure management (44%) are used on many dairy farms in the province of Québec, Canada. However, this could change in the near future because the rise in average herd size and the popularity of milking robots are such that the industry expects an increase in free-stall dairies managing manure with liquid systems. This shift could affect the carbon (C), nitrogen (N), and phosphorus (P) footprints of Québec's dairy production. In this context, whole-farm modeling (N-CyCLES), considering all the production cycle, provides a tool for evaluating the economics and environmental impacts of standard housing and manure management systems (Part I) in combination with different mitigation approaches (Part II). Two representative dairy farms in southwestern Québec (SWQ; 45.3° N, 73.2° W) and eastern Québec (EQ; 48.45° N, 68.1° W) were simulated considering four scenarios involving combinations of tie-stall or free-stall housing and solid or liquid manure management. Maximum farm net income (FNI) was $0.33 and $0.18 kg-1 of fat- and protein-corrected milk (FPCM) for the SWQ and EQ farms, respectively, with N and P footprints of 12.22 to 16.99 g N kg-1 and 0.52 to 0.79 g P kg-1 of FPCM in SWQ, and 11.48 to 15.39 g N kg-1 and 1.41 to 1.88 g P kg-1 of FPCM in EQ. Greenhouse gas (GHG) emissions reached 1.78 to 1.87 kg CO2e kg-1 and 1.67 to 1.71 kg CO2e kg-1 of FPCM in SWQ and EQ, respectively. The SWQ farm was associated with greater production of cash crops but also greater imports of fertilizers and purchased feeds, which negatively affected the N footprint and GHG emissions. Housing and manure management types did not influence FNI. Free-stall dairies were associated with greater N surpluses. Nevertheless, they emitted slightly less GHG than tie-stall dairies. Dairy farms under liquid manure management imported less fertilizers and produced less GHG despite greater CH4 emissions. As a result, the current transition toward free-stall barns and liquid manure systems in Québec seems advantageous from an environmental standpoint without compromising economic profitability. [ABSTRACT FROM AUTHOR]

The present survey, based on a multiple-choice questionnaire, was undertaken to assess the gastrointestinal tolerance of four commercial diets from the Veterinary HPMTM diet range. The four diets were tested in 284 adult dogs over a 28-day period and compared to their usual diets. Online evaluations were performed at the beginning of the study, at the end of the 4-day diet transition, and at 7, 14 and 28 days. Digestive sensitivity with the dog's usual food was reported in 28% of the enrolled dogs. At least 94% of the pet owners declared they were satisfied with the transition to the tested diets. Average stool consistency scores with the tested diets remained steady at the optimal value of 2.2. Globally acceptable stool odour and small or normal stool volume were reported in over 70% of the dogs. Unchanged or decreased faeces odour and volume were described in more than 70% of the dogs and unchanged or increased stool consistency was reported in more than 77% of the dogs in comparison to their previous diet. Faecal consistency and stool volume were not significantly different between the different time points. The number of dogs showing flatulence was significantly lower on days 7, 14 and 28 than on day 0. In conclusion, a safe diet transition and a high digestive tolerance was reported after feeding various-sized adult dogs of different breeds with the tested Veterinary HPMTM diets. [ABSTRACT FROM AUTHOR]

The digestive tolerance of three commercial diets (Baby Dog Small & Toy, Baby Dog Large & Medium, and Junior Dog Special Large) issued from a new high proteinlow carbohydrate diet range, Veterinary HPMTM, was assessed in growing dogs through an online survey administered to 129 pet owners over a 28-day testing period, and was compared to that of the dogs' usual diets. Multiple-choice questionnaires had to be filled out at the beginning of the study, at the end of a 4-day diet transition, and after 7, 14, and 28 days. About 30% of the enrolled dogs had previously shown a digestive sensitivity with their usual food, mainly manifested as diarrhoea. In the present study, more than 94% of the pet owners were satisfied with the way the transition to the tested diets had taken place. Volume, consistency, and odour of the stools showed little change when switching diets, and were not significantly different between the different time points for each tested diet. The percentage of dogs with flatulence on days 7, 14, and 28 (except for one diet) significantly decreased compared to day 0. In conclusion, the three tested Veterinary HPMTM diets enabled a safe diet transition from numerous kinds of canine foods. The tested diets have all shown a high digestive tolerance in various-sized puppies and growing dogs of different breeds. [ABSTRACT FROM AUTHOR]

Background: Like innate cells, B cells also express Pattern Recognition Receptors (PRRs) to detect danger signal such as tissue damage or pathogen intrusion. Production of specific antibodies by plasma cells results from the activation and differentiation of B cells following three signals: (i) antigen recognition by B Cell Receptors, (ii) recognition of danger and (iii) T-cell help. However, it is unclear whether T-cell help is dispensable for B cell activation and differentiation or not. Few studies have investigated the role of cytosolic PRRs such as NOD1 in B cell differentiation., Methods: We used splenic C57BL6J B cells to evaluate NOD1 expression and then assessed the effect of stimulation with C12-iE-DAP, a NOD1 ligand, with or without CD40L as a T-cell help signal on B-cell responses globally or according to their CD23 expression level., Results: We showed that murine B cells express NOD1 and that the presence of C12-iE-DAP induces activation, proliferation and initiates differentiation in plasma cells even in the absence of a T-dependent signal. Surprisingly, CD23 high B cells are more sensitive than CD23 low B cells to stimulation., Conclusion: Our results suggest that the NLR pathway could induce antibody development during infections and be exploited to develop more effective vaccination.

The recently developed mRNA-based coronavirus SARS-CoV-2 vaccines highlighted the great therapeutic potential of the mRNA technology. Although the lipid nanoparticles used for the delivery of the mRNA are very efficient, they showed, in some cases, the induction of side effects as well as the production of antibodies directed against particle components. Thus, the development of alternative delivery systems is of great interest in the pursuit of more effective mRNA treatments. In the present work, we evaluated the mRNA transfection capacities of a series of cationic histidine-rich amphipathic peptides derived from LAH4. We found that while the LAH4-A1 peptide was an efficient carrier for mRNA, its activity was highly serum sensitive. Interestingly, modification of this cell penetrating peptide at the N-terminus with two tyrosines or with salicylic acid allowed to confer serum resistance to the carrier., (© 2024 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

The physiological problem of chronic inflammation and its associated pathologies attract ongoing attention with regard to methods for their control. Current systemic pharmacological treatments present problematic side effects. Thus, the possibility of new anti-inflammatory compounds with differing mechanisms of action or biophysical properties is enticing. Cationic polymers, with their ability to act as carriers for other molecules or to form bio-compatible materials, present one such possibility. Although not well described, several polycations such as chitosan and polyarginine, have displayed anti-inflammatory properties. The present work shows the ubiquitous laboratory transfection reagent, polyethylenimine (PEI) and more specifically low molecular weight branched PEI (B-PEI) as also possessing such properties. Using a RAW264.7 murine cell line macrophage as an inflammation model, it is found the B-PEI 700 Da as being capable of reducing the production of several pro-inflammatory molecules induced by the endotoxin lipopolysaccharide. Although further studies are required for elucidation of its mechanisms, the revelation that such a common lab reagent may present these effects has wide-ranging implications, as well as an abundance of possibilities., (© 2024 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Woodchips in stand-off pads for wintering cows have been applied in countries like Ireland and New Zealand. Their primary role is to protect soils by effectively filtering nutrients during wet conditions, while ensuring a healthy and comfortable environment for the cows. The stand-off pad concept has the potential to be adopted in Canada to provide year-long outdoor access to tie-stall dairy cows. The objective of this study was to evaluate the effect of alternative filtering materials and bed aeration under controlled laboratory conditions. Twelve biofilter columns (0.3 m in diameter and 1-m high) were installed in 12 environmentally-controlled chambers (1.2-m wide by 2.4-m long), and divided into four treatments: a bed of conventional woodchips or an alternative mix of organic materials (sphagnum peat moss, woodchips and biochar) with and without aeration (flux rate set at 0.6 m 3 /min/m 2 ). Approximately 0.6 L of semi-synthetic dairy manure and 1 L of tap water were poured on the biofilters during two experimental periods of 4 weeks, simulating the effect of either winter or summer conditions (room temperature below or over 10 °C) on the retention of nutrients and fecal bacteria. Results showed that the alternative biofilters under both summer and winter conditions were more efficient in removing COD, SS, TN, and NO 3 -N than conventional biofilters (maximum efficiencies of 97.6%, 99.7%, 96.4%, and 98.4%, respectively). Similarly for E. coli, they achieved a minimum concentration of 1.8 Log 10  CFU/100 ml. Conventional biofilters were more efficient for PO 4 -P removal with a maximum efficiency of 88.2%. Aeration did not have any significant effect under the tested temperature conditions. Additional factors such as media adaptation time as well as aeration flow during this period should be considered., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Elizabeth Alvarez Chavez reports financial support was provided by Laval University. Elizabeth Alvarez Chavez reports financial support was provided by Research and Development Institute for the Agri-Environment. Elizabeth Alvarez Chavez reports financial support was provided by Quebec Ministry of Agriculture Fisheries and Food., (Copyright © 2023. Published by Elsevier Ltd.)

A growing body of experimental and clinical evidence suggests that rare cell populations, known as cancer stem cells (CSCs), play an important role in the development and therapeutic resistance of several cancers, including glioblastoma. Elimination of these cells is therefore of paramount importance. Interestingly, recent results have shown that the use of drugs that specifically disrupt mitochondria or induce mitochondria-dependent apoptosis can efficiently kill cancer stem cells. In this context, a novel series of platinum(II) complexes bearing N-heterocyclic carbene (NHC) of the type [(NHC)PtI 2 (L)] modified with the mitochondria targeting group triphenylphosphonium were synthesized. After a complete characterization of the platinum complexes, the cytotoxicity against two different cancer cell lines, including a cancer stem cell line, was investigated. The best compound reduced the cell viability of both cell lines by 50% in the low μM range, with an approximately 300-fold higher anticancer activity on the CSC line compared to oxaliplatin. Finally, mechanistic studies showed that the triphenylphosphonium functionalized platinum complexes significantly altered mitochondrial function and also induced atypical cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC's sensitivity to such compounds is thus described.

Our multicentric, masked, controlled and randomised study aimed to assess the efficacy and safety of Suprelorin® 4.7 mg (Virbac, Carros, France) regarding oestrus prevention in prepubertal intact bitches. Twelve- to eighteen-week-old females (n = 83) were allocated either a deslorelin implant (n = 62) or 0.9% sodium chloride (n = 21) group. Clinical assessment (heat signs), 17β oestradiol and progesterone assays, and vaginal cytology were performed at day (D)0, D7, D21, month (M)3 and M6 after product administration, and were then performed every other month until reaching puberty. Trained owners assessed heat signs between each veterinary visit. All bitches (n = 83) reached puberty before M30. Deslorelin significantly extended the median time to sexual maturity when compared to the control group (377 days versus 217 days after D0, p < 0.0001). Three females, implanted between 16 and 18 weeks of age, expressed an induced oestrus. Additional descriptive data, collected over a 24 month-period, showed functional reproductive abilities in both deslorelin (n = 52) and control (n = 21) groups once puberty was achieved. In conclusion, Suprelorin® 4.7 mg seems to be an effective and safe option for postponing the onset of oestrus when administered to prepubertal female dogs aged from 12 to 16 weeks.

Cancer stem cells (CSCs) represent a difficult to treat cellular niche within tumours due to their unique characteristics, which give them a high propensity for resistance to classical anti-cancer treatments and the ability to repopulate the tumour mass. An attribute that may be implicated in the high rates of recurrence of certain tumours. However, other characteristics specific to these cells, such as their high dependence on mitochondria, may be exploited for the development of new therapeutic agents that are effective against the niche. As such, a previously described phosphorescent N-heterocyclic carbene iridium(III) compound which showed a high level of cytotoxicity against classical tumour cell lines with mitochondria-specific effects was studied for its potential against CSCs. The results showed a significantly higher level of activity against several CSC lines compared to non-CSCs. Mitochondrial localisation and superoxide production were confirmed. Although the cell death involved caspase activation, their role in cell death was not definitive, with a potential implication of other, non-apoptotic pathways shown. A cytostatic effect of the compound was also displayed at low mortality doses. This study thus provides important insights into the mechanisms and the potential for this class of molecule in the domain of anti-CSC therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The difficulty involved in the treatment of many tumours due to their recurrence and resistance to chemotherapy is tightly linked to the presence of cancer stem cells (CSCs). This CSC sub-population is distinct from the majority of cancer cells of the tumour bulk. Indeed, CSCs have increased mitochondrial mass that has been linked to increased sensitivity to mitochondrial targeting compounds. Thus, a platinum-based polyethylenimine (PEI) polymer-drug conjugate (PDC) was assessed as a potential anti-CSC therapeutic since it has previously displayed mitochondrial accumulation. Our results show that CSCs have increased specific sensitivity to the PEI carrier and to the PDC. The mechanism of cell death seems to be necrotic in nature, with an absence of apoptotic markers. Cell death is accompanied by the induction of a protective autophagy. The interference in the balance of this pathway, which is highly important for CSCs, may be responsible for a partial reversion of the stem-like phenotype observed with prolonged PEI and PDC treatment. Several markers also indicate the cell death mode to be capable of inducing an anti-cancer immune response. This study thus indicates the potential therapeutic perspectives of polycations against CSCs.

Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial, yeast, and/or fungal infections. In this context, new implant materials and coatings that deal with medical device-associated complications are required. Antibacterial and anti-inflammatory materials are also required for wound healing applications, especially in diabetic patients with chronic wounds. In this work, hyaluronic acid (HA) hydrogels with triple activity: antimicrobial, immunomodulatory, and miRNA delivery agent, are presented. It is demonstrated that polyarginine with a degree of polymerization of 30 (PAR30), which is previously shown to have a prolonged antibacterial activity, decreases inflammatory response of lipopolysaccharide-stimulated macrophages. In addition, PAR30 accelerates fibroblast migration in macrophage/fibroblast coculture system, suggesting a positive effect on wound healing. Furthermore, PAR30 allows to load miRNA into HA hydrogels, and then to deliver them into the cells. To the authors knowledge, this study is the first describing miRNA-loaded hydrogels with antibacterial effect and anti-inflammatory features. Such system can become a tool for the treatment of infected wounds, e.g., diabetic ulcers, as well as for foreign body response modulation., (© 2022 Wiley-VCH GmbH.)

Background: Metals are trace elements, vital in some instances or toxic in others. Due to this toxicity, they have been used since ancient time as antimicrobials, and prescribed when plant-only remedies were not efficient enough. These remedies could still contain secrets that may lead to the discovery of new therapeutically interesting combinations. The objective of this study was to give a proof of concept that such remedies combining metals and plants are worth studying again., Methods: We exploited 4 medical formularies (aqrābādhīn), from three Arab authors from the 9-12th century. We reproduced a remedy, and analyzed the role of each ingredient. We further looked for the minimum inhibitory concentration against three pathogenic bacteria, and we analyzed toxic and inflammatory effects of this remedy on macrophages., Results: Even if plants were extensively used (almost 80 % of all ingredients), more than 36 different minerals have been found in these 4 aqrābādhīn. When it came to remedies against infections that could be applied externally, the use of metals grew to 70 %. We focused on a remedy, containing mainly metals. We have been able to attribute a role for each ingredient, to show that this skin remedy helped to combat the infection and to resorb the wound, and to highlight the mastering of metal transformation by these physicians., Conclusions: With a very simple recipe, mainly composed of metals, these past physicians designed a complete and synergistic remedy to combat abscesses, while restricting the toxic effect of metals to the site of infection. It is a first example showing that different metal manufactures were evolved to improve their therapeutic potentials. The knowledge acquired by these physician should deserve more attention, and unexpected features, original organo-metallic compounds or therapeutic synergy could still be found from such research., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

The main objectives of this work were to formulate liposomes encapsulating highly mineralized thermal waters (TWs) and to study anti-inflammatory effect of free and encapsulated thermal waters on RAW 264.7 macrophage cells stimulated with lipopolysaccharide (LPS). TWs-loaded conventional and deformable liposomes (TWs-Lip and TWs-DLip) were prepared by sonication and extrusion, respectively. They were considered for their vesicle size, zeta potential, entrapment efficiency, physical stability and in vitro anti-inflammatory effect. Formulated liposome suspensions have a low polydispersity and nanometric size range with zeta potential values close to zero. The vesicle size was stable for 30 days. Entrapment efficiency of TWs was above 90% in conventional liposomes and 70% in deformable liposomes. Pretreatment of LPS-stimulated murine macrophages, with free and liposome-encapsulated TWs, resulted in a significant reduction in nitric oxide (NO) production and modulated tumor necrosis factor-α (TNF-α) production suggesting an anti-inflammatory effect which was even more striking with TWs-Lip and TWs-DLip. Liposome formulations may offer a suitable approach for transdermal delivery of TWs, indicated in inflammatory skin diseases., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recycled manure solids (RMS) produced in dairy farms from fresh manure need to be sanitized before using them as bedding material. However, the impact on air quality of composting RMS remains unknown. Four RMS composting methods were tested during a 10-day aging of piles in experimental chambers: static windrow (SW), turned windrow (TW), SW following drum composting for 24 h (DC24) or SW following drum composting for 72 h (DC72). Air samples were collected using a SASS®3100 Dry Air Sampler on days 0 (pilling of the RMS), 5, and 10. Bacteria (16S rRNA genes), Penicillium/Aspergillus, A fumigatus , and 11 human pathogenic bacteria (e.g. Klebsiella pneumonia ) were quantified by qPCR while endotoxins and dust particles were, respectively, measured by LAL assays and with a DustTrak TM DRX Aerosol Monitor. On day 0, RMS produced by SW and TW yielded the lowest concentrations of airborne bacteria, while DC24 resulted in the lowest levels of Penicillium/Aspergillus and dust particles. SW method led on day 5 to the lowest concentration of bacteria and Penicillium/Aspergillus , and DC24 and DC72 to the lowest concentration of airborne dust. On day 10, SW and TW piles were associated with the lowest levels of Penicillium/Aspergillus and dust particles. A significant difference was observed between concentration of airborne bacteria, Penicillium/Aspergillus and endotoxins before and during the turnover of TW piles. None of the studied human pathogens was detected in the air samples. Results of the present study suggest that SW and TW are the most promising methods for the production of composted RMS with respect to microbial air quality. However, the experimental chambers do not accurately represent commercial dairy barns and further research on these composting methods is necessary. Finally, the study highlights that bedding material and its management may be determinant factors for air quality in dairy barns. Implications : The research evaluated the impact on microbial air quality of composting recycled manure solids (RMS) produced from fresh cow manure. RMS need to be composted or sanitized before using them as bedding material for animals. The impact on animal health of RMS still needs to be confirmed, while the effect on air quality and the health of dairy farmers is unknown. In the present study, microbial air quality associated with four RMS composting methods was investigated. Data revealed that two methods resulted in lower aerosolization of dust particles, endotoxins, molds, and bacteria.

Implants and prostheses are widely used to replace damaged tissues or to treat various diseases. However, besides the risk of bacterial or fungal infection, an inflammatory response usually occurs. Here, recent progress in the field of anti-inflammatory biomaterials is described. Different materials and approaches are used to decrease the inflammatory response, including hydrogels, nanoparticles, implant surface coating by polymers, and a variety of systems for anti-inflammatory drug delivery. Complex multifunctional systems dealing with inflammation, microbial infection, bone regeneration, or angiogenesis are also described. New promising stimuli-responsive systems, such as pH- and temperature-responsive materials, are also being developed that would enable an "intelligent" antiinflammatory response when the inflammation occurs. Together, different approaches hold promise for creation of novel multifunctional smart materials allowing better implant integration and tissue regeneration., (© 2020 Wiley-VCH GmbH.)

Animal welfare concerns have been a challenging issue for producers and international marketing. In laying hen production, cage-free systems (CFS) have been identified as an alternative to ensure the laying hens' well-being. Nevertheless, in CFS, important environmental issues have been reported, decreasing indoor air quality. Environmental control strategies (ECS) have been designed to enhance indoor air quality in CFSs. However, little information exists about the effect of these ECSs on natural animal behaviors. Four strategies and one control were tested in an experimental CFS, previously designed to track behavioral variables using video recordings over seven time-lapses of 1 hour per day. Spatial occupancy (SO) and laying hen behaviors (LHB) were registered. One statistical analysis was applied to evaluate the effect of ECS on SO and LHB using a multinomial response model. Results show lower chances to use litter area within the reduction of litter allowance treatment (T17) ( p < 0.05). Neither the four ECSs nor the control implemented in this experiment affected the natural behaviors of the hens. However, stress patterns and high activity were reported in the T17 treatment. This study shows that it is possible to use these ECSs without disrupting laying hens' natural behaviors.

Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which leads to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8 + T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Founded in 1919, the Society of Biology of Strasbourg (SBS) is a learned society whose purpose is the dissemination and promotion of scientific knowledge in biology. Subsidiary of the Society of Biology, the SBS celebrated its Centenary on Wednesday, the 16th of October 2019 on the Strasbourg University campus and at the Strasbourg City Hall. This day allowed retracing the various milestones of the SBS, through its main strengths, its difficulties and its permanent goal to meet scientific and societal challenges. The common thread of this day was the transmission of knowledge related to the past, the present, but also the future. At the start of the 21st century, the SBS must continue to reinvent itself to pursue its objective of transmitting scientific knowledge in biology and beyond. Scientific talks performed by senior scientists and former SBS thesis prizes awardees, a round table, and informal discussions reflected the history and the dynamism of the SBS association. All SBS Centennial participants have set the first milestone for the SBS Bicentennial., (© Société de Biologie, 2020.)

Therapeutic cancer vaccines need thoughtful design to efficiently deliver appropriate antigens and adjuvants to the immune system. In the current study, we took advantage of the versatility of a liposomal platform to conceive and customize vaccines containing three elements needed for the induction of efficient antitumor immunity: i) a CD4 epitope peptide able to activate CD4 + T helper cells, ii) a CD8 tumor-specific epitope peptide recognized by CD8 + T cytotoxic cells and iii) Pattern Recognition Receptor (PRR) agonists which stand as adjuvants. Each type of component, conjugated to liposomes, was evaluated individually by comparing their vaccine efficacy after immunization of naïve mice. These screening steps resulted in the optimization of three liposomal constructs bearing a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant, which displayed antitumor efficiency against a mouse model of disseminated tumors transformed by HPV16. Our results validated the interest of our customizable liposomal platform as delivery system for cancer vaccination. We also demonstrated its interest as tool for vaccine design allowing the strategical selection of components, and the evaluation of epitope-adjuvant association., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.

The high interest in N -Heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed on 8 different types of cells that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. Using HCT116 cells, the conjugates displayed an effective activity after only 45 min of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

Nowadays, the need for therapeutic biomaterials displaying anti-inflammatory properties to fight against inflammation-related diseases is continuously increasing. Compact polyelectrolyte complexes (CoPECs) represent a new class of materials obtained by ultracentrifugation of a polyanion/polycation complex suspension in the presence of salt. Here, a noncytotoxic β-cyclodextrin-functionalized chitosan/alginate CoPEC was formulated, characterized, and described as a promising drug carrier displaying an intrinsic anti-inflammatory property. This new material was successfully formed, and due to the presence of cyclodextrins, it was able to trap and release hydrophobic drugs such as piroxicam used as a model drug. The intrinsic anti-inflammatory activity of this CoPEC was analyzed in vitro using murine macrophages in the presence of lipopolysaccharide (LPS) endotoxin. In this model, it was shown that CoPEC inhibited LPS-induced TNF-α and NO release and moderated the differentiation of LPS-activated macrophages. Over time, this kind of bioactive biomaterial could constitute a new family of delivery systems and expand the list of therapeutic tools available to target inflammatory chronic diseases such as arthritis or Crohn's disease.

Tumor Necrosis Factor Receptor Apoptosis Inducing Ligand (TRAIL) appears as an interesting candidate for targeted cancer therapy as it induces apoptosis in cancer cells without toxicity to normal cells. TRAIL elicits apoptosis through agonist death receptor TRAIL-R1 and TRAIL-R2 engagement. Nevertheless, recombinant soluble TRAIL and monoclonal antibodies against these receptors demonstrated insufficient efficacy in clinical trials. This may be explained by the cell-type dependency of the apoptotic response, itself influenced by the effect on ligand binding mode of factors such as the level of receptor oligomerization or glycosylation. To investigate the relation between binding mode and signaling, we used previously described synthetic divalent and monovalent peptides specific for TRAIL-R2. We measured their pro-apoptotic activity on three cancer cell lines sensitive to rhTRAIL induced-apoptosis and monitored their cell-surface binding kinetics. The two divalent peptides bound with strong affinity to TRAIL-R2 expressed on B lymphoma BJAB cells and induced a high degree of apoptosis. By contrast, the same peptides bound weakly to TRAIL-R2 expressed at the surface of the human colon cancer HCT116 or T lymphoma Jurkat cell lines and did not induce their apoptosis. Cross-linking experiments suggest that these differences could be afforded by variations in the TRAIL-R2 oligomerization state at cell surface before ligand addition. Moreover divalent peptides showed a different efficiency in BJAB apoptosis induction, and kinetic distribution analysis of the BJAB binding curves suggested subtle differences in binding mechanisms. Thus our data support a relation between the cell-surface binding mode of the peptides and their pro-apoptotic activity. In this case the precise characterization of ligand binding to the surface of living cells would be predictive of the therapeutic potential of TRAIL-R2 synthetic ligands prior to clinical trials., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Physical oncology is an emerging paradigm which recognizes tissue mechanics, per se, as an active modulator of tumorigenesis, treatment resistance and clinical outcome, mediated by mechanosignaling pathways, matrix remodeling and physical barriers to drugs. The tumor microenvironment displays abnormal physical properties in comparison to healthy tissue which contribute to cancer progression and resistance to current treatments. Physical aberrancies comprise the chaotic organization of tumor vasculature, an increased interstitial pressure, an increased solid stress, hypoxia, an abundant extracellular matrix and a progressive stiffening of solid tumors. The physical barriers in tumors are of critical importance, as tissue mechanics compromises drug delivery, reduces immune cell infiltration and promotes disease aggressiveness. All these physical hallmarks of cancer, although not fully understood, are inspiring new anticancer strategies aiming to target and normalize the physical anomalies of solid tumors, particularly in the field of nanomedicine. Here we summarize the recent paradigm shift of physical oncology and review some of the proposed strategies using nanomaterials to tackle the tumor microenvironment and its aberrant physical properties. Nanomedicine might harness the features of the tumor microenvironment in order to improve nanoparticle and drug delivery, or propose nano-agents that can be activated on demand to achieve a tailored spatio-temporal modulation of the tumor microenvironment, reduce tumor pressure and stiffness and alleviate the resistance to current treatments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)