A bioactive substance carrier includes a bioactive substance and porous silica particles supporting the bioactive substance and having a plurality of pores with a diameter of 5 nm to 100 nm. The porous silica particles have particular physical properties, can deliver all various drugs by a supported amount in a sustained manner, and can be parenterally administered.

A method of treating cancer in a subject, including: providing a subject having a plurality of cancer cells; and administering to the subject, a therapeutically effective amount of a composition including: an HDM-2 binding component; and a membrane resident component, the membrane resident component bound to the HDM-2 binding component. Also provided are a method of selectively necrosing cancer cells, a method of causing membranolysis in cancer cells, and a cancer treatment composition.

Compositions, systems and methods of improving the health of the microbiome of an individual's skin relate to the provision of skin contacting formulations containing beneficial bacteria and other microbe components to foster the growth and maintenance of a healthy skin microbiome. Embodiments include methods for treating an individual suffering from acne vulgaris by topically administering a composition that includes live bacteria selected from the group consisting of L. reuteri, L. johnsonii, L. crispatus, C. acnes, and Nitrosomonas eutropha, that have been modified by using a using a clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR associated protein (Cas) system or a CRISPR from Prevotella and Francisella 1(Cpf1) system to reduce the production of a virulence factor of the bacteria.

A method for treating an individual suffering from a chronic infectious disease and who has cancer employs a CRISPR system to selectively kill or reduce the numbers of pathogenic bacteria within the individual and the individual is then administered an immune checkpoint inhibitor. In particular embodiments, the pathogenic bacteria is one of E. coli, Pseudomonas aeruginosa and Klebsiella bacteria, and the checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. Further embodiments include enhancing the growth of a second bacteria in the individual, such bacteria including Akkermansia, Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Fusobacterium, Coprococcus, LactoBacillus, Propionibacterium, Ruminococcus, Veillonella, Prevotella, Escherichia and Streptococcus. The CRISPR system may include Cas9, Cpf1 and Cas3, and may be delivered using a bacteriophage.

A method for treating an individual suffering from one of bladder cancer and colorectal cancer employs a CRISPR system to selectively kill or reduce the numbers of pathogenic bacteria within the individual and the individual is then administered an immune checkpoint inhibitor. In particular embodiments, the pathogenic bacteria is one of E. coli, Pseudomonas aeruginosa and Klebsiella bacteria, and the checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. Further embodiments include enhancing the growth of a second bacteria in the individual, such bacteria including Akkermansia, Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Fusobacterium, Lactobacillus, Propionibacterium, Ruminococcus, Veillonella, Prevotella, Escherichia and Streptococcus. Still other embodiments include increasing the levels of Roseburia and/or Faecalibacterium prausnitzii, in the individual's gut microbiome.

A person's intestinal (gut), oral or skin microbiota is modified using specific combinations of pre-biotics, pro-biotics and/or anti-biotics to establish a defined microbiota that can treat and/or reduce the likelihood that individuals will experience various diseases, including cancer. The employment of various bacteria, whether in particular combinations or after being modified using CRISPR-type systems, leads to improved outcomes when checkpoint inhibitors are used to treat various forms of cancer. One embodiment is directed to a method for reducing the likelihood of developing cancer by providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of Lactobacillus species. The level of Roseburia and Faecalibacterium prausnitzii, and/or Akkermansia muciniphila bacteria are increased in the individual's gut microbiome such that when an individual is administered an immune checkpoint inhibitor, its function is enhanced due to the presence of the bacterial population.

A method for treating an individual suffering from one of bladder cancer and colorectal cancer employs a CRISPR system to selectively kill or reduce the numbers of pathogenic bacteria within the individual and the individual is then administered an immune checkpoint inhibitor. In particular embodiments, the pathogenic bacteria is one of E. coli, Pseudomonas aeruginosa and Klebsiella bacteria, and the checkpoint inhibitor is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. Further embodiments include enhancing the growth of a second bacteria in the individual, such bacteria including Akkermansia, Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Fusobacterium, Lactobacillus, Propionibacterium, Ruminococcus, Veillonella, Prevotella, Escherichia and Streptococcus. Still other embodiments include increasing the levels of Roseburia and/or Faecalibacterium prausnitzii, in the individual's gut microbiome.

Various embodiments of the present invention are directed to the field of treating and preventing osteoporosis, with particular embodiments directed to a method of ameliorating, treating, or preventing osteoporosis in a human subject employing tomatidine, xylitol, rapamycin, etc., as well as modifying an individual's microbiome to reduce the likelihood of osteoporosis.

A method for reducing the likelihood of developing depression in an individual involves providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of bacterial species able to make small chain fatty acids, and preferably butyrate, and administering fiber to the individual to maintain a therapeutically effective amount of the beneficial bacteria in the gut of the individual. The individual's gut microbiome is modified to reduce the number of undesired bacteria and to increase the number of beneficial bacteria. Bacteria are preferably modified to remove one or more virulence facts or alternatively to produce increased amounts of SCFA's, such as butyrate. Beneficial bacteria may be encapsulated in a frangible enclosure to ensure they arrive in an individual's body while still viable, e.g. such as being first released in the lower gut rather than being exposed to the harsh conditions of an individual's stomach. In other embodiments, a therapeutically effective amount of a bacterial formulation comprising Faecalibacterium prausnitzii is administered. Other embodiments include the administration of a bacterial formulation comprising at least one of Coprococcus, Roseburia, Bifidobacterium, Faecalibacterium prausnitzii and L. casei to treat depression.

The present disclosure is directed to methods and compositions for inhibiting a cancer cell using nucleic acid sequences encoding elephant p53 or elephant p53 amino acid sequences.