Abstract: The present invention provides for compounds of Formula I-I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R1, R2, R3, X1, X2, A and Cy variable in Formula I-I all have the meaning as defined herein.

Abstract: Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K?) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3K? plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K?, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K? activity, including compounds that selectively inhibit PI3K? activity. Methods of using PI3K? inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K? inhibitory compounds to inhibit PI3K?-mediated processes in vitro and in vivo.

Abstract: The invention relates to spiro deriviatives, to the use of said derivatives in treating diseases and conditions mediated by modulation of voltage-gated sodium channels, to compositions containing said derivatives and processes for their preparation.

Abstract: A combination of a CDK4/6 inhibitor and a P3Kinase inhibitor for the treatment of cancer.

Abstract: The present invention relates to a new use of phosphodiesterase 1 (PDE1) inhibitors for the treatment of psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder, delusional disorder, mania, or bipolar disorder.

Abstract: Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

Abstract: Provided herein are Aminopurine compounds of Formula I: or pharmaceutically acceptable salts, tautomers, isotopologues, or stereoisomers thereof, wherein R1, R2, and R3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing animal and human protozoal infections.

Abstract: The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

Abstract: The use of cobalt porphyrins for the manufacture of an agent for mobilizing bone marrow cells to peripheral blood, preferably used to treat congenital neutropenia, for the treatment and prevention of neutropenia caused by chemotherapy, radiotherapy and pharmacologically-induced neutropenia, for the treatment of acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, and to increase the amount of circulating hematopoietic stem cells in peripheral blood for subsequent isolation in the process of apheresis and allogeneic or autologous transplantation.

Abstract: In one aspect, this disclosure describes a pharmaceutical composition that generally includes frankiamicin A and a pharmaceutically acceptable carrier. In another aspect, this disclosure describes a method of treating a subject having, or at risk of having, a condition caused by a microbial infection treatable with frankiamicin A. Generally, the method includes administering to the subject an amount of frankiamicin A effective to ameliorate at least one symptom or clinical sign of the condition.

Abstract: Use of a derivative containing C—O—P bonds in a controlled release form to treat patients with kidney failure. Moreover, it comprises the use of said derivatives together with other active substances, which particularly may be selected from a list comprising a calcimimetic, vitamin, phosphate binder, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent.

Abstract: In an effort to discover therapies for treating HSP70 related diseases, a previously unidentified hydrophobic pocket was found in the C-terminal domain of DnaK and of human HSP70. A novel chemical scaffold was also discovered for identifying compounds that treat diseases related to this hydrophobic pocket. The compounds have the structure of the formula (I), wherein L, M, and R1-R5 are defined herein and are, therefore, in these therapies, optionally with other pharmaceutical agents such as genotoxic agents. Accordingly these compounds are useful in inhibiting HSP70 or DnaK, reducing HSP70 in mitochondria of a cancer cell, treating malignant neoplastic disease, or inhibiting or reducing bacterial growth. These compounds also resulted in novel methods of screening for a HSP70 inhibitor or DnaK inhibitor by using the three-dimensional structure of the hydrophobic pocket in DnaK or HSP70.

Abstract: The present disclosure relates to a method of treating cancer using a composition including a target-specific self-illuminative nanocomplex which includes a self-illuminative nanocomplex including a quantum dot and a modified self-illuminative protein (m-Rluc8), a targeted cancer-specific molecule and a hydrophilic polymer, and a method of preparing the composition. Since the high efficiency self-illuminative nanocomplex may have high target specificity by chemically binding to a target-specific molecule, it can be effectively used in cancer treatment using a nanometer-scale laser light source, and therefore it is expected to propose a new paradigm of nanoptic therapeutics.

Abstract: Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

Abstract: The present invention is a sterile peritoneal dialysis fluid, including an acidic first liquid containing 60.0 to 94.0 g/L of icodextrin and 0 to 2.34 g/L of sodium chloride, and an alkaline second liquid containing an alkaline pH regulator, in which the first liquid after sterilization has a pH of 5.0 to 5.5, the second liquid after sterilization has a pH of 6.5 to 7.5, and a mixture of the first liquid and the second liquid after sterilization has a pH of 6.0 to 7.5. The present invention can provide a peritoneal dialysis fluid containing icodextrin, in which the stability of icodextrin during the heat sterilization and the subsequent storage can be improved to the maximum, and the pH of the peritoneal dialysis fluid is close to the physiological range.

Abstract: The present invention relates to a novel pharmaceutical composition with milk of immunized camelid, particularly Camelus dromedarius as the main component (i.e. active ingredient) and a method for the treatment or prevention of skin or mucus membrane infections, particularly Acne vulgaris. The present invention also discloses a process of preparing said composition.

Abstract: Methods are provided for stimulating ovarian preantral and antral follicles in a mammal.

Abstract: The invention provides methods and compositions useful for ameliorating age related maladies, enhancing and maintaining immune function, enhancing and maintaining cognitive function, enhancing and maintaining muscle strength, enhancing and maintaining balance, and reducing and mitigating oxidative stress in an animal. The compositions comprise a combination of at least two of one or more unsaturated fatty acids (UFA); one or more nitric oxide releasing compounds (NORC); one or more anti-glycation agents; and colostrum, and the methods comprise administering to an animal a therapeutically effective amount of the compositions.

Abstract: This disclosure discloses new krill oil compositions characterized by having high amounts of phospholipids, astaxanthin esters and/or omega-3 contents. The krill oils are obtained from krill meal using supercritical fluid extraction in a two stage process. Stage 1 removes the neutral lipid by extracting with neat supercritical CO2 or CO2 plus approximately 5% of a co-solvent. Stage 2 extracts the actual krill oils by using supercritical CO2 in combination with approximately 20% ethanol. The krill oil materials obtained are compared with commercially available krill oil and found to be more bioeffective in a number of areas such as anti-inflammation, anti-oxidant effects, improving insulin resistances and improving blood lipid profile.

Abstract: A method and system of reducing the likelihood of an inflammatory disease developing by providing a mucosal adhesive strip to a subject, with the strip provided with at least one of a plurality of agents effective to hinder the growth of spirochetes bacteria in a subject's oral cavity. In certain embodiments, an effective amount of Prevotella intermedia is provided to decrease the incidence of periodontitis and to reduce the progression of Alzheimer's disease. In still other embodiments, the likelihood that a subject will suffer from Alzheimer's disease is reduced by administering via local gingival application to a subject that has been diagnosed with periodontitis an effective amount of an antibiotic effective to kill spirochetes bacteria residing on the subgingival tooth area of the subject.

Abstract: The instant invention relates to seaweed extract compositions, processes for isolation, isolated active agents, and methods of treating disease, disorders and conditions in a subject, including, reactive oxygen species (ROS)-mediated diseases and diseases mediated through the activation of the Nrf2-ARE (antioxidant response element) pathway, including proliferative diseases and disorders, Alzheimer's disease, stroke, and certain diseases and disorders of aging and associated with aging and exposure, by use of the extracts, compounds, and compositions thereof.

Abstract: Preparation process for dietary supplements, comprising at least two steps, the first step of which is to obtain a basic composition comprising liquid vegetable extracts (that contain alcohol), essential oils, water and optionally powdered vegetable extracts, mineral elements, vitamins, vegetable oils, marine plasma, organic silica, etc., and the second step of which is used to solidify the mixture by adding a solidifying premix comprising alginates, a vegetable gum and optionally solidification retarders such as dry hydrophilic plants, water chelators or other substances, even chemicals. The advantage of the process is that it enables dietary supplements to be obtained in a dry solid state that can be stored at ambient temperature or in a refrigerator, and is stable over time, without losing the nutritional and therapeutic value of the vegetable or natural substances contained therein.

Abstract: The present invention includes a method of activating irisin by administering to an individual in need of such treatment a composition comprising irisin-activating ingredients, thus increasing the conversion of white fat to BAT, and consequently, increasing metabolic rate and promoting weight loss. In an embodiment, the composition includes a Gynostemma pentaphyllum extract, a Polygonum cuspidatum root extract, capsaicinoids, and grains of paradise or constituents thereof. The composition may optionally comprise additional ingredients to activate the increased BAT, thus further increasing metabolic rate and furthering weight loss.

Abstract: Described herein are compositions and methods of treatment for musculoskeletal pain.

Abstract: The present invention relates to a functional engineered rice having alcoholism relief and liver protection functions for those drinking alcohol over an extended period of time or drinking alcohol excessively, and preparation method thereof. The engineered rice comprises six starting materials: coarse rice powder, isolated soy protein, kudzu root extract, corn oligopeptide, purple sweet potato powder, and hawthorn extract, and is prepared by: premixing the starting materials; employing a double screw extruder to conduct texturized processing and forming under high temperature and high pressure; and then drying, dedusting and packaging.

Abstract: A silk peptide having neuroprotective and neurofunctional activities and its preparation method are discussed. One method relates to preparing silk protein preferably having neuroprotective activity with weight average molecular weight of 200-100,000 by hydrolysis of silk fibroin; also discussed are a composition for preventing or treating brain disease comprising silk peptide and pharmaceutically acceptable carrier, and a composition for improving brain function.

Abstract: Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

Abstract: The present disclosure relates to the control of fungal infection of horn-like envelopes covering dorsal and terminal phalanges in humans and animals and related cerebral protrusions in animals as well as keratin comprising material on surfaces of humans and animals. Agents and natural and synthetic formulations and extracts useful for the control of fungal infection of these envelopes and related protrusions and keratin comprising material are also encompassed by the subject disclosure. In an embodiment, the present disclosure teaches the treatment of fungal infection of nails and in particular onychomycosis in humans.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Abstract: The invention provides for peptides from syndecan 1 and methods of use therefor. These peptides can inhibit ?4?6 interaction with HER2, thereby preventing tumor cell growth and tissue invasion. The peptides can further be used to inhibit scarring and/or to inhibit pathologic neovascularization in a subject.

Abstract: The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.

Abstract: The described invention provides methods for treating an inflammatory brain disease, disorder or condition and for treating a traumatic brain injury having an inflammatory component in a subject in need thereof using isolated erythropoietin (EPO)-derived oligopeptides.

Abstract: The invention provides for the use of carbonic anhydrase activators; protein kinase C activators and FGF-18 to treat depressive disorders. The invention also relates to improved animal models and methods for screening and identifying compounds to treat depressive disorders.

Abstract: Methods to reduce the proliferation of vestibular schwannoma (VS) cells and/or provide neuroprotection to reduce the risk of sensorineural hearing loss (SNHL), vestibular dysfunction and facial nerve paralysis in subjects with VS. The methods can include one or more of decreasing TNF-? activity or expression; decreasing NF-?B expression or activity; decreasing COX-2 expression or activity; administering FGF2; decreasing HGF expression or activity; or decreasing c-Met expression or activity.

Abstract: Nerve Growth Factor (NGF), in the form of a preparation to be administered over ocular surface, is suggested as being suitable for therapy and/or prophylaxis of intraocular tissue pathologies, with particular reference to sclera, ciliary body, crystalline lens, retina, optic nerve, vitreous body and choroidea affections. When administered in the form of external ophthlamic preparation, for example as collyrium or ointment, NGF is capable to go through ocular tissues and it has been found out that it shows a therapeutic activity not only against retina and optic nerve pathologies but also against affections involving the above reported internal structures of the eye.

Abstract: The invention relates to (among other things) method of administering to a patient suffering from a cancer, the method comprising the steps of: (a) an IL-2R?-activating amount of a long acting, IL-2R?-selective agonist; and (b) a CTLA-4 pathway-inhibiting amount of an anti-CTLA-4 antibody or a PD-1 pathway-inhibiting amount of an anti-PD-1 antibody.

Abstract: Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided, More particularly, the present disclosure relates to optimized dosing parameters to achieve and maintain efficacy in the treatment and/or prevention of metabolic diseases, disorders and conditions in a subject, while minimizing the adverse effects associated therewith. Particular embodiments are directed to the treatment and/or prevention of abnormally high levels of cholesterol and/or manifestation(s) of hypercholesterolemia in as subject.

Abstract: Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

Abstract: Pharmaceutical compositions and kits including a tyrosine hydroxylase inhibitor; melanin, a melanin promoter, or a combination thereof; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor are provided. Also provided are methods of treating cancer in a subject, comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof. Also provided are methods of reducing cell proliferation in a subject comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof.

Abstract: The present invention relates to the use of a nucleic acid that comprises a sequence encoding an APOBEC3A protein, in preventing or treating a tumor in a patient.

Abstract: The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a tumor antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of cancer or tumor diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a tumor antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

Abstract: The present invention provides methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated oropharyngeal tumor or cancer, comprising the step of administering to a subject a recombinant Listeria strain expressing a human papillomavirus antigen.

Abstract: Compositions are provided comprising a replication-competent herpesvirus vector system and/or a herpesvirus vector particle comprising a heterologous recombinant transgene of interest encoding an antigen of interest (e.g., a tumor-associated antigen, a microbial antigen, etc.), wherein the recombinant transgene has been modified to comprise a codon usage signature of a herpesvirus late gene operably linked to an active promoter. Such compositions find use in a variety of methods including, for example, methods of generating an immune response against an antigen of interest in a subject in need thereof, as well as methods for treating or preventing cancer or a microbial infection.

Abstract: Embodiments of the invention comprise an improved vaccine for generating an immune response and preventing or treating mycobacterial diseases such as tuberculosis in humans and animals. Embodiments of the invention also comprise a method for using the vaccine against such mycobacterial diseases.

Abstract: Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Abstract: Recombinant strains of Mycobacterium bovis bacille Calmette-Guerin (M. bovis BCG) comprising a heterologous nucleic acid sequence of Mycobacterium marinum (M. marinum) are provided. In some embodiments the heterologous nucleic acid sequence of M. marinum comprises a plurality of open reading frames, wherein the plurality of open reading frames comprise open reading frames that encode proteins each at least 95% homologous to the Mycobacterium marinum (M. marinum) proteins MMAR5445, MMAR5446, MMAR5447, MMAR5448, MMAR5449, MMAR5450, MMAR5451, MMAR5452, MMAR5453, and MMAR5455. In some embodiments the plurality of open reading frames further comprise an open reading frame that encodes a protein at least 95% homologous to the M. marinum proteins MMAR5443, MMAR5444, and MMAR5457. In some embodiments the plurality of open reading frames further comprise open reading frames that encode proteins at least 95% homologous to the M.

Abstract: The present invention relates to protecting against, treating, and detecting Fusobacteria infections. Compositions and methods derived from nucleic acid and protein sequences of a 40 kDa Adhesin protein are provided to protect against, treat, and detect Fusobacteria infections in a subject. In one aspect, vaccines capable of inducing an immune response to a 40 kDa Adhesin protein are used to protect against Fusobacteria infection. Also, nucleic acid molecules, proteins, immunogens, antibodies, and antisense molecules derived from the sequences of the 40 kDa Adhesin protein may be used to protect against, treat, and detect Fusobacteria infections in a subject.