Novel proteins and compounds conjugated with polysialic acid (PSA) are provided herein. Also provided are methods of using these compounds and methods of treatment of various diseases and disorders. The novel compounds provided herein have improved pharmacodynamic and/or pharmacokinetic properties, improved effectiveness, and other desirable properties.

The present disclosure provides biomarker panels for evaluating subjects at risk of sinusoidal obstruction syndrome (SOS) early after hematopoietic stem cell transplantation (HSCT). In particular, the present disclosure relates to the use of ST2. L-Ficolin, and HA for prognosing, diagnosing, and/or treating SOS.

Invention; is about the kit that enables three-dimensional healing with the platelet-rich fibrin framework support used in hard and soft tissue healing.

Acute kidney injury (AKI) is often associated with damage to remote organs, such as lungs or heart. AKI induces kidney tubular necrosis as well as NETosis, programmed neutrophil death leading to neutrophil extracellular traps (NETs). Histones released during NETosis induces further formation of NETs, which is damaging to renal tissues and remote organs. Circulating trap-forming neutrophils directly injured the lung, while other dead tissue releases contributed to injury in other organs. Suppressing renal necroinflammation using inhibitors of NET formation, tubular cell necrosis or extracellular histones prevented kidney as well as remote organ injuries. Dual inhibition of neutrophil trap formation together with tubular cell necrosis had an additive protective effect. Preferably, damage to remote organs induced by AKI may be treated and/or prevented using anti-histone agents such as anti-histone IgG, recombinant activated protein C, or heparin, alone or in combination with other therapeutic agents, such as PAD inhibitors.

Acute kidney injury (AKI) is often associated with damage to remote organs, such as lungs or heart. AKI induces kidney tubular necrosis as well as NETosis, programmed neutrophil death leading to neutrophil extracellular traps (NETs). Histones released during NETosis induces further formation of NETs, which is damaging to renal tissues and remote organs. Circulating trap-forming neutrophils directly injured the lung, while other dead tissue releases contributed to injury in other organs. Suppressing renal necroinflammation using inhibitors of NET formation, tubular cell necrosis or extracellular histones prevented kidney as well as remote organ injuries. Dual inhibition of neutrophil trap formation together with tubular cell necrosis had an additive protective effect. Preferably, damage to remote organs induced by AKI may be treated and/or prevented using anti-histone agents such as anti-histone IgG, recombinant activated protein C, or heparin, alone or in combination with other therapeutic agents, such as PAD inhibitors.

The present invention relates to a method for treating a bone loss disease, condition, or disorder in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a composition comprising thrombomodulin lectin-like domain (TMD1).

A method for blocking, inhibiting and/or decreasing cluster of differentiation 14 (CD14) function, CD14-mediated cellular response and/or treating CD14-mediated pathological conditions is disclosed. The method comprises administering to a subject in need thereof a pharmaceutical composition comprising: (a) a therapeutically effective amount of a recombinant protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 1, wherein the recombinant protein does not comprises a lectin-like domain 1 of a human thrombomodulin; and (b) a pharmaceutically acceptable vehicle, carrier, diluent, excipients, and/or salt.

Severe glomerulonephritis involves cell necrosis as well as NETosis, programmed neutrophil death leading to expulsion of nuclear chromatin and neutrophil extracellular traps (NETs). Histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells. This was prevented by histone-neutralizing agents anti-histone IgG, activated protein C and heparin. Histone toxicity on glomeruli was TLR2/4-dependent. Anti-GBM glomerulonephritis involved NET formation and vascular necrosis. Pre-emptive anti-histone IgG administration significantly reduced all aspects of glomerulonephritis, including vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment and activation of glomerular leukocytes and glomerular crescent formation. Subjects with established glomerulonephritis treated with anti-histone IgG, recombinant activated protein C, or heparin all abrogated severe glomerulonephritis suggesting that histone-mediated glomerular pathology is a subsequent, not initial event in necrotizing glomerulonephritis. Neutralizing extracellular histones is therapeutic in severe experimental glomerulonephritis.

Severe glomerulonephritis involves cell necrosis as well as NETosis, programmed neutrophil death leading to expulsion of nuclear chromatin and neutrophil extracellular traps (NETs). Histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells. This was prevented by histone-neutralizing agents anti-histone IgG, activated protein C and heparin. Histone toxicity on glomeruli was TLR2/4-dependent. Anti-GBM glomerulonephritis involved NET formation and vascular necrosis. Pre-emptive anti-histone IgG administration significantly reduced all aspects of glomerulonephritis, including vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment and activation of glomerular leukocytes and glomerular crescent formation. Subjects with established glomerulonephritis treated with anti-histone IgG, recombinant activated protein C, or heparin all abrogated severe glomerulonephritis suggesting that histone-mediated glomerular pathology is a subsequent, not initial event in necrotizing glomerulonephritis. Neutralizing extracellular histones is therapeutic in severe experimental glomerulonephritis.

A method for blocking, inhibiting and/or decreasing cluster of differentiation 14 (CD14) function, CD14-mediated cellular response and/or treating CD14-mediated pathological conditions is disclosed. The method comprises administering to a subject in need thereof a pharmaceutical composition comprising: (a) a therapeutically effective amount of a recombinant protein comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 1, wherein the recombinant protein does not comprises a lectin-like domain 1 of a human thrombomodulin; and (b) a pharmaceutically acceptable vehicle, carrier, diluent, excipients, and/or salt.