Disclosed herein are synthetic hydrogels suitable for delivering antimicrobial proteins, optionally in combination with bone regenerating agents to injured tissues. The hydrogels can include lysostaphin and one or more bone morphogenic proteins. The hydrogels are composed of a network of crosslinked hydrophilic polymers and adhesion peptides.

Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S(HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency. In particular, the inventors showed that TREM-1 inhibition is particular suitable for limiting the severity of vaso-occlusions. The results obtained by the inventors also suggest that plasmatic concentration of sTREM-1 could be a reliable biomarker for predicting vaso-occlusions and/or SCD-associated organ dysfunction and end-organ damage.

Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S(HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency. In particular, the inventors showed that TREM-1 inhibition is particular suitable for limiting the severity of vaso-occlusions. The results obtained by the inventors also suggest that plasmatic concentration of sTREM-1 could be a reliable biomarker for predicting vaso-occlusions and/or SCD-associated organ dysfunction and end-organ damage.

The present invention relates to diagnostic methods to assess the presence of quorum sensing molecules (QSM), preferably peptides (QSPs), that influence muscle wasting in humans. The present invention furthermore relates to the use of the knowledge obtained by the diagnostic method in order to influence muscle wasting diseases in animals and human, by for example providing bacteria that produce beneficial QSMs or non-harmful QSMs, providing antagonists for harmful QSMs and the like.

The present invention relates to diagnostic methods to assess the presence of quorum sensing molecules (QSM), preferably peptides (QSPs), that influence muscle wasting in humans. The present invention furthermore relates to the use of the knowledge obtained by the diagnostic method in order to influence muscle wasting diseases in animals and human, by for example providing bacteria that produce beneficial QSMs or non-harmful QSMs, providing antagonists for harmful QSMs and the like.

Described herein are pharmaceutical compositions containing peptoids of general formula (I), (II), or (III) capable of reducing proliferation of cancer stem cells in a subject and methods of treatment or prophylactic administration of these pharmaceutical compositions to treat cancer. Also provided herein are method of detecting and treating cancerous cell masses by use of peptoids of general formula (I), (II), or (III).

The present invention provides a vaccine against a coronavirus. According to the present invention, there is provided a peptide consisting of the amino acid sequence set forth in SEQ ID NO: 1 or a partial peptide of a coronavirus spike protein consisting of the amino acid sequence corresponding to the amino acid sequence of SEQ ID NO: 1 and a multiple antigen peptide containing a plurality of any of these peptides.

The present disclosure provides binding agents that modulate the interaction between liver-expressed antimicrobial peptide 2 (LEAP2) and growth hormone secretagogue receptor (GHSR). Specifically, the present disclosure provides binding agents, such as LEAP2 peptides that bind GHSR and methods of their use to treat or ameliorate a neuroendocrine and/or metabolic disease or disorder such as obesity, diabetes, acromegaly, gigantism and/or Prader-Willi syndrome. The present disclosure also provides binding agents, such as antibodies, that bind LEAP2, and methods of their use to, e.g., treat or ameliorate a neuroendocrine and/or metabolic disease or disorder such as cachexia, anorexia, or other wasting syndromes, increase growth hormone levels, or increase GHSR activity.

Disclosed are methods, systems, components, and compositions for cell-free synthesis of glycosylated proteins. The glycosylated proteins may be utilized in vaccines, including anti-bacterial vaccines. The glycosylated proteins may include a bacterial polysaccharide conjugated to a carrier, which may be utilized to generate an immune response in an immunized host against the polysaccharide conjugated to the carrier. The glycosylated proteins may be synthesized in cell-free glycoprotein synthesis (CFGpS) systems using prokaryote cell lysates that are enriched in components for glycoprotein synthesis such as oligosaccharyltransferases (OSTs) and lipid-linked oligosaccharides (LLOs) including OSTs and LLOs associated with synthesis of bacterial O antigens.

Disclosed are methods, systems, components, and compositions for cell-free synthesis of glycosylated proteins. The glycosylated proteins may be utilized in vaccines, including anti-bacterial vaccines. The glycosylated proteins may include a bacterial polysaccharide conjugated to a carrier, which may be utilized to generate an immune response in an immunized host against the polysaccharide conjugated to the carrier. The glycosylated proteins may be synthesized in cell-free glycoprotein synthesis (CFGpS) systems using prokaryote cell lysates that are enriched in components for glycoprotein synthesis such as oligosaccharyltransferases (OSTs) and lipid-linked oligosaccharides (LLOs) including OSTs and LLOs associated with synthesis of bacterial O antigens.