The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.

The present invention provides compounds, compositions thereof, and methods of using the same.

The present invention relates to a method for detecting malignant kidney cancer in an individual, said method conducted in vitro comprising the steps of providing a body fluid sample, in particular a urine sample, obtained from the individual, and determining one or more biomarker levels selected from the group consisting of the Mxi-2 level, the Vim3 level, the MAPKp38 level and the Atg7 level in the sample. Further, the present invention refers to a kit and a dipstick for use in such method.

A codon optimization method based on an immune algorithm is characterized in that an immune algorithm and a genetic algorithm are successively used to respectively perform local multi-objective optimization and global multi-objective optimization on a protein coding sequence, and then an exhaustive method is used to perform fine adjustment and optimization on the sequence, so as to search the optimal expression sequence to the greatest extent. The present invention not only retains the characteristic of random global parallel search of the genetic algorithm, but also avoids premature convergence to a comparatively great extent to ensure rapid convergence to the global optimal solution. The present invention is the first to combine the advantages of the immune algorithm and the genetic algorithm in accuracy and efficiency to carry out codon optimization through a step-by-step process (local optimization, global optimization, and fine adjustment and optimization respectively in sequence), and proves the high efficiency of the algorithm in codon optimization through example tests.

Provided herein, inter alia, are p38 mitogen-activated protein kinase inhibitors and methods of treating cancer using p38 mitogen-activated protein kinase inhibitors

The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, orZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.

The invention relates to inhibitors of MAPK3 (ERK1 MAP kinase), in particular to polypeptides having the ability to stimulate the global ERK signalling pathway in the brain and their use as neuroprotective and/or cognitive enhancing agents. The invention also concerns related polynucleotides, vectors, host cells and pharmaceutical compositions able to inhibit MAPK3, causing the stimulation of the global ERK signalling pathway. Additionally, use of the afore inhibitors or stimulators in the treatment of neurodegenerative or neuropsychiatric disorders and cognitive impairment is also disclosed.

The present invention relates to compositions and methods of inhibiting p38 kinase to reduce gene and protein expression of DUX4 and downstream genes regulated by DUX4. The present invention further relates to methods for treating patients suffering from diseases associated with increased expression of DUX4 or expression of an aberrant form of DUX4, such as Facioscapulohumeral muscular dystrophy (FSHD).

The instant disclosure provides methods and compositions for the diagnosis, treatment and prevention of Marfan syndrome and related diseases, disorders and conditions. The disclosure further provides pharmaceutical compositions and kits for the diagnosis, treatment and prevention of Marfan syndrome and related diseases, disorders and conditions.

The present invention provides compounds, compositions thereof, and methods of using the same.