The present invention relates to the seminal discovery that P-selectin glycoprotein ligand-1 (PSGL-1) modulates the immune system and immune responses. Specifically, the present invention provides PSGL-1 agonists and antagonists which increase the survival of multifunctional T cells and viral clearance. The present invention further provides methods of treating infectious diseases, cancer and immune and inflammatory diseases and disorders using a PSGL-1 modulator.

Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.

The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

The present invention discloses a preparation method for a disubstituted PEGylated interleukin 2, which comprises the steps of: (1) PEGylating IL-2 to obtain a crude product of a PEGylated interleukin; (2) performing gel chromatography filtration to remove free interleukin 2 from the crude product; (3) performing affinity chromatography on the product in the step (2) by means of an α receptor column, and collecting a flow-through peak component and an elution peak component; (4) performing ion exchange separation on the flow-through peak component and the elution peak component in the step (3); and (5) collecting components of the disubstituted PEGylated interleukin 2.

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

Provided is a DNT cell population with IL-17 secretory cells removed and a preparation method therefor and the use thereof. The DNT cell population has the effects of inhibiting T cell proliferation and inducing apoptosis, can inhibit the inflammation of adipose tissue, improve insulin resistance, alleviate diabetes, and relieve steatohepatitis, and can also be used for preventing and treating antigen-specific allergic asthma.

The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

Disclosed are compounds having the formula:

##STR00001## wherein q, r, s, A, B, C, R.sup.A1, R.sup.A2, R.sup.B1, R.sup.B2, R.sup.C1, R.sup.C2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.14, R.sup.15, R.sup.16, and R.sup.17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.