WR BIOTECH, LLC - Florida Company Profile

813-442-3341

wrbiotech@outlook.com

RUISHENG LIU

Self-Certified Small Disadvantaged Business

P2479908

HLVEXZFJKCF2

8MVD8

2025-10-25

2024-10-31

2020-06-23

2023-09-07

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Department of Health and Human Services

PROTECTION OF TRANSPLANTED HEART FUNCTION BY REGULATION OF NA/K PUMP ACTIVITY - THE OBJECTIVE OF THIS PROPOSAL IS TO EXAMINE A NOVEL TECHNIQUE CALLED IMPROVED SYNCHRONIZATION MODULATION ELECTRIC FIELD (I-SMEF) IN THE PROTECTION OF DONOR HEARTS AND IMPROVEMENT OF TRANSPLANTED GRAFT FUNCTIONS. WE WILL APPLY THE I-SMEF ON DONOR HEARTS DURING STATIC COLD STORAGE AND EVALUATE THE TRANSPLANTED GRAFT FUNCTION FOLLOWING HEART TRANSPLANTATION IN MICE. HEART TRANSPLANTATION (HTX) REMAINS THE BEST THERAPEUTIC OPTION FOR ADVANCED-STAGE HEART FAILURE, AS WELL AS FOR COMPLEX CONGENITAL HEART DISEASE, RESTRICTIVE CARDIOMYOPATHY, AND SOME INFECTIOUS DISEASES. HOWEVER, THE LONG-TERM SURVIVAL RATE OF THE HEART GRAFT HAS ONLY SHOWN A SMALL IMPROVEMENT DURING THE PAST DECADES, WITH A MEDIAN SURVIVAL ABOUT 12.5 YEARS. IN ADDITION, THE MAXIMAL TIME FOR STATIC COLD STORAGE IS USUALLY ABOUT 5 HOURS. LONGER STORAGE TIME IS ASSOCIATED WITH HIGHER RATES OF BOTH EARLY AND LATE GRAFT FAILURE. THE DEVELOPMENT OF NEW STRATEGY FOR EXTENSION OF STORAGE TIME THEREBY INCREASING THE DONOR POOL AND IMPROVEMENT OF THE TRANSPLANTED GRAFT FUNCTION ARE UNMET NEEDS. ONE OF THE PROMINENT CHALLENGES IN HTX IS ISCHEMIA REPERFUSION INJURY (IRI) TO THE GRAFT. IRI IS A MAJOR FACTOR FOR BOTH EARLY AND LATE GRAFT FAILURE AND MORTALITY. FOLLOWING HYPOXIA, DUE TO POOR ATP SUPPLY, ACTIVITY OF THE NA+/K+-ATPASE (NA/K PUMP) SLOWS DOWN OR STOPS, WHICH IS ONE OF THE EARLIEST AND CRITICAL IMPAIRMENTS FOLLOWING ISCHEMIA. REDUCTION IN THE NA/K PUMP FUNCTION DISRUPTS THE EQUILIBRIUM OF CELLULAR ION CONCENTRATIONS, CELL VOLUME AND MEMBRANE POTENTIAL, WHICH CAN CAUSE DAMAGE TO ALL CELLULAR COMPONENTS (E.G., MITOCHONDRIA), APOPTOSIS AND NECROSIS. THEREFORE, MAINTAINING THE NA/K PUMP FUNCTION FOLLOWING ISCHEMIA COULD BE A VITAL INITIAL STRATEGY FOR THE PROTECTION OR PREVENTION OF THE ISCHEMIC INJURY. WE HAVE DEVELOPED A NOVEL TECHNIQUE, NAMED THE I-SMEF (PATENT PENDING, CHEN AND LIU), WHICH CAN NOT ONLY MAINTAIN THE PUMP FUNCTIONS, BUT ALSO GENERATE ATP MOLECULES. BASED ON STRONG PRELIMINARY FINDINGS, WE PROPOSE TO TEST THIS TECHNIQUE IN A MOUSE HTX MODEL. WE WILL TEST OUR HYPOTHESIS THAT APPLICATION OF THE I-SMEF ON DONOR HEARTS DURING COLD STORAGE PROTECTS AGAINST ISCHEMIC INJURY AND IMPROVES THE TRANSPLANTED GRAFT FUNCTIONS.

275739.00

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0.00

2022-09-16

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Department of Health and Human Services

PROTECTION OF DONOR KIDNEYS WITH SYNCHRONIZATION MODULATION ELECTRIC FIELD (SMEF) - THE GOALS OF THIS PHASE II APPLICATION: 1) DETERMINE THE TRANSLATIONAL SIGNIFICANCE OF THE I-SMEF (IMPROVED SYNCHRONIZATION MODULATION ELECTRIC FIELD) IN A PRECLINICAL ANIMAL MODEL USING ADULT YORKSHIRE PIGS WITH KIDNEY AUTOTRANSPLANTATION; AND 2) DETERMINE THE OPTIMAL PARAMETERS OF THE I-SMEF IN PROTECTION AGAINST ISCHEMIC INJURY OF THE DONOR KIDNEYS DURING COLD STORAGE AND IMPROVEMENT OF THE TRANSPLANTED GRAFT FUNCTION. IN THE PHASE I PROPOSAL, WE HAVE DEVELOPED A NOVEL TECHNIQUE, NAMED I-SMEF (PATENT PENDING). THE I-SMEF NOT ONLY CONTROLS THE NA/K PUMP ACTIVITY, BUT ALSO GENERATES ATP MOLECULES. BRIEFLY, BY UTILIZING THE INTRINSIC DUAL ENERGY TRANSFORM FUNCTIONS OF THE NA/K PUMPS, WE SPECIALLY DESIGNED THE I-SMEF TO CONTROL NA/K PUMP ACTIVITY. MEANWHILE, THE ELECTRIC FIELD PROVIDES ADEQUATE ENERGY TO THE PUMP MOLECULES SO THAT THEY CAN SYNTHESIZE ONE ATP MOLECULE FOR EACH PUMPING CYCLE. CONSEQUENTLY, THE I-SMEF CAN MAINTAIN THE NA/K PUMPING ACTIVITY IN SITUATIONS WITH AN INSUFFICIENT OR LACK OF ATP SUPPLY, SUCH AS IN HYPOXIA. THEN, WE DEMONSTRATED THAT THE APPLICATION OF THE I-SMEF ON THE DONOR KIDNEYS EFFECTIVELY PROTECTED TRANSPLANTED GRAFT FUNCTIONS IN A MOUSE KIDNEY TRANSPLANTATION MODEL. THESE DATA HAVE JUST BEEN PUBLISHED IN SCIENCE TRANSLATIONAL MEDICINE. IN THIS PHASE II PROPOSAL, WE WILL EXAMINE THE TRANSLATIONAL SIGNIFICANCE OF THE I-SMEF BY USING A PRECLINICAL PORCINE MODEL IN ADULT YORKSHIRE PIGS. TO MINIMIZE THE IMMUNORESPONSE AND FOCUS ON THE ISCHEMIA REPERFUSION INJURY, WE WILL USE KIDNEY AUTOTRANSPLANTATION MODEL. THEN, WE WILL DETERMINE THE OPTIMAL PARAMETERS, INCLUDING THE NUMBERS OF ELECTRODE PAIRS, FREQUENCY, AND VOLTAGE. CONSIDERING THE HIGH SIMILARITIES IN SIZE, ANATOMY AND PHYSIOLOGY BETWEEN HUMAN AND ADULT PIG KIDNEYS, WE BELIEVE THAT THE OPTIMAL PARAMETERS OBTAINED FROM PIGS ARE READILY APPLICABLE TO HUMANS IN THE PHASE III PROPOSAL.

1681073.90

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0.00

2021-09-23

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Department of Health and Human Services

PROTECTION OF DONOR KIDNEYS WITH SYNCHRONIZATION MODULATION ELECTRIC FIELD (SMEF) - THE OBJECTIVE OF THIS PROPOSAL IS TO EXAMINE A NOVEL TECHNIQUE CALLED IMPROVED SYNCHRONIZATION MODULATION ELECTRIC FIELD (I-SMEF) IN PROTECTION OF DONOR KIDNEYS AND IMPROVEMENT OF TRANSPLANTED GRAFT FUNCTIONS. WE WILL APPLY THE I-SMEF ON DONOR KIDNEYS DURING COLD STORAGE AND EVALUATE THE TRANSPLANTED GRAFT FUNCTION FOLLOWING KIDNEY TRANSPLANTATION IN MICE. WE HAVE DEVELOPED A NOVEL TECHNIQUE, NAMED I-SMEF, WHICH COULD NOT ONLY MAINTAIN THE PUMP FUNCTIONS, BUT ALSO GENERATE ATP MOLECULES. BRIEFLY, ON THE ONE HAND, I-SMEF MAINTAINS NA/K PUMP ACTIVITY TO ACTIVELY TRANSPORT THREE NA+ OUT AND TWO K+ IONS IN BY CONSUMING ONE ATP MOLECULE, ON THE OTHER HAND, THE ELECTRIC FIELD PROVIDES ENERGY TO THE PUMP MOLECULES SO THAT THEY CAN SYNTHESIZE ONE ATP IN EACH PUMPING CYCLE. CONSEQUENTLY, THE ATP NET-CONSUMPTION FOR THE I-SMEF-CONTROLLED NA/K PUMPS IS THEORETICALLY ZERO AT ANY PUMPING RATE, IN OTHER WORDS, THE PUMP MOLECULES CAN EFFECTIVELY BUILD UP PHYSIOLOGICAL IONIC CONCENTRATION GRADIENTS IN THE SITUATIONS WITH A LIMITED OR LACK OF ATP SUPPLY, SUCH AS IN HYPOXIA. BASED ON THE STRONG PRELIMINARY FINDINGS, WE PROPOSE TO TEST THIS TECHNIQUE IN A MOUSE KIDNEY TRANSPLANTATION MODEL. WE WILL TEST OUR HYPOTHESIS THAT APPLICATION OF THE I-SMEF ON DONOR KIDNEYS DURING COLD STORAGE PROTECTS AGAINST ISCHEMIC INJURY AND IMPROVES THE TRANSPLANTED GRAFT FUNCTIONS.

177663.10

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