Provided are bispecific proteins that comprise a binding domain binding cell surface protein and a vascular endothelial growth factor (VEGF) inhibiting domain. Provided also is an antibody-drug conjugate that comprises a therapeutic agent and an antibody or an antigen-binding fragment binding PD-L1 and/or a VEGF inhibiting domain, wherein the therapeutic agent is covalently conjugated to the antibody or the antigen-binding fragment by a linker.

The present invention is intended to identify a modulatory substance of the tumor immune microenvironment, and to provide a therapeutic utilization method of the modulatory substance. Specifically, the present invention relates to an inhibitor of the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TIME), wherein the inhibitor comprises, an active ingredient, a substance that suppresses or inhibits the function of an immunomodulator released from dead tumor cells. More specifically, the present invention relates to the aforementioned inhibitor comprising a substance that suppresses or inhibits the function of, for example, TCTP (translationally controlled tumor protein).

Methods of treating patients having inflammatory bowel disease (IBD) or primary sclerosing cholangitis (PSC) are provided herein.

This invention teaches a targeted apheresis method of treating a pregnant woman with preeclampsia, or who is predisposed to developing preeclampsia, utilizing immobilized binding agents contained within an apheresis device to remove sVEGFR-1 and sVEGFR-2, and one or more other harmful factors associated with preeclampsia selected from a list that includes: sEndoglin, Endothelin-1, TNF, IL-1, IL-6, IL-12, IL-18, digitalis-like factor, ouabain-like factor, marinobufagenin, .marinobufotoxenin, and telocinobufagin. The binding agents used are antibodies or aptamers or binding peptides. Reducing the concentration of sVEGFR-1, sVEGFR-2 and other harmful factors in the pregnant woman's blood using targeted apheresis will alleviate or delay the symptoms of preeclampsia, and thus postpone premature delivery of the baby so that the baby is born at term or as close to term as possible.

An exemplary embodiment of the present disclosure provides a composition comprising two or more cytokines, and one or more of keratan sulfate, chondroitin sulfate, or hyaluronic acid. The composition can simulate a fluid from a patient. The simulated fluid has a viscosity, a storage modulus, and a loss modulus similar to that of patient-derived synovial fluid. A method for making a composition for simulating a fluid from a patient is also disclosed. The method includes creating a mixture comprising two or more cytokines, and one or more of keratan sulfate, chondroitin sulfate, or human serum albumin. The method also includes adding a low molecular weight hyaluronic acid to the mixture, adding a high molecular weight hyaluronic acid to the mixture, and incubating the mixture for a predetermined time at a temperature ranging from approximately 0° C. to approximately 10° C.

Provided are systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an angiogenic and anti-angiogenic imbalance. Also provided are methods of treating an angiogenic and anti-angiogenic imbalance with water-soluble statins, such as pravastatin.

The present invention corresponds to the field of cancer and is related to predicting cancer detection, diagnosis, monitoring and prediction of response to treatment, in particular platelet derived-endothelial cell growth factor (PD-ECGF) levels for their use as a potential value in monitoring disease evolution and predicting response to anti-angiogenic treatment.

The present application relates to the fields of tumor treatment and molecular immunology, and specifically, to an anti-VEGFA/PD-1 bifunctional antibody, a pharmaceutical composition thereof and use thereof. Specifically, the anti-VEGFA/PD-1 bifunctional antibody comprises a first protein functional region targeting VEGFA and a second protein functional region targeting PD-1. The bifunctional antibody can specifically bind to VEGFA and PD-1, specifically relieve immunosuppression of VEGFA and PD-1 in an organism, and inhibit tumor-induced angiogenesis, thus having good application prospect.

Markers of an intense scarring process in the early phase post-myocardial infarction (MI) are still undetermined, and the identification of patients at higher risk of developing large adverse fibrotic remodeling and heart failure remains challenging. Here, the inventors demonstrate the modulation in the paracrine behavior of resident PW1+ cells in scarring cardiac tissue post-MI and the differential abundance of 12 candidate markers in their secretome. Of these, growth differentiation factor 3 (GDF3), a member of transforming growth factor-β family, upregulates proliferation of cardiac fibroblasts, which are instrumental in fibrosis. GDF3 is upregulated in the scarred tissue and plasma of mice and humans post-MI, with the highest plasma levels predicting higher fibrotic cardiac remodeling and cardiac dilation. The inventors thus reveal the previously unidentified function of GDF3 in predicting adverse fibrotic cardiac remodeling post-MF Thus the present invention relates to the use of GDF3 as biomarker and biotarget in post-ischemic cardiac remodeling.

Methods for diagnosing or monitoring endometriosis in a mammal are provided. The methods include the steps of determining the expression levels of BDNF, glycodelin and optionally ZAG, in a biological sample from the mammal, and determining that the mammal has endometriosis when the biomarker expression levels in the sample are elevated.