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The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs’ potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects. The present study reports successful manifestation of LHON-like symptoms in rats and demonstrates the potential of the NDI1 gene therapy on mitochondrial optic neuropathies. Our results indicate a window of opportunity for the gene therapy to be applied successfully after the onset of the disease symptoms.

Failure of central nervous system (CNS) axons to regenerate after injury results in permanent disability. Several molecular neuro-protective and neuro-regenerative strategies have been proposed as potential treatments but do not provide the directional cues needed to direct target-specific axon regeneration. Here, we demonstrate that applying an external guidance cue in the form of electric field stimulation to adult rats after optic nerve crush injury was effective at directing long-distance, target-specific retinal ganglion cell (RGC) axon regeneration to native targets in the diencephalon. Stimulation was performed with asymmetric charged-balanced (ACB) waveforms that are safer than direct current and more effective than traditional, symmetric biphasic waveforms. In addition to partial anatomical restoration, ACB waveforms conferred partial restoration of visual function as measured by pattern electroretinogram recordings and local field potential recordings in the superior colliculus—and did so without the need for genetic manipulation. Our work suggests that exogenous electric field application can override cell-intrinsic and cell-extrinsic barriers to axon regeneration, and that electrical stimulation performed with specific ACB waveforms may be an effective strategy for directing anatomical and functional restoration after CNS injury.

The GFDL hurricane modeling system, initiated in the 1970s, has progressed from a research tool to an operational system over four decades. This system is still in use today in research and operations, and its evolution will be briefly described. This study used an idealized version of the 2014 GFDL model to test its sensitivity across a wide range of three environmental factors that are often identified as key factors in tropical cyclone (TC) evolution: SST, atmospheric stability (upper-air thermal anomalies), and vertical wind shear (westerly through easterly). A wide range of minimum central pressure intensities resulted (905–980 hPa). The results confirm that a scenario (e.g., global warming) in which the upper troposphere warms relative to the surface will have less TC intensification than one with a uniform warming with height. The TC rainfall is also investigated for the SST–stability parameter space. Rainfall increases for combinations of SST increase and increasing stability similar to global warming scenarios, consistent with climate change TC downscaling studies with the GFDL model. The forecast system’s sensitivity to vertical shear was also investigated. The idealized model simulations showed weak disturbances dissipating under strong easterly and westerly shear of 10 m s−1. A small bias for greater intensity under easterly sheared versus westerly sheared environments was found at lower values of SST. The impact of vertical shear on intensity was different when a strong vortex was used in the simulations. In this case, none of the initial disturbances weakened, and most intensified to some extent.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain’s visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases. Researchers have developed a noninvasive retina prosthesis based on ultrasound for treating blindness. This device uses ultrasound waves to stimulate the retina, creating artificial vision confirmed through behavior tests, offering a safer alternative to invasive treatments.

End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a “total retina patch” consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch’s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina.

Stem cell therapy offers significant promise for tissue regeneration and repair. Traditionally, bone marrow- and adipose-derived stem cells have served as primary sources, but their clinical use is limited by invasiveness and low cell yield. This review focuses on body fluid-derived stem cells as an emerging, non-invasive, and readily accessible alternative. We examine stem cells isolated from amniotic fluid, peripheral blood, cord blood, menstrual fluid, urine, synovial fluid, breast milk, and cerebrospinal fluid, highlighting their unique biological properties and therapeutic potential. By comparing their characteristics and barriers to clinical translation, we propose body fluid-derived stem cells as a promising source for regenerative applications, with continued research needed to fully achieve their clinical utility.

The Princeton Ocean Model for Tropical Cyclones (POM-TC), a version of the three-dimensional primitive equation numerical ocean model known as the Princeton Ocean Model, was the ocean component of NOAA’s operational Hurricane Weather Research and Forecast Model (HWRF) from 2007 to 2013. The coupled HWRF–POM-TC system facilitates accurate tropical cyclone intensity forecasts through proper simulation of the evolving SST field under simulated tropical cyclones. In this study, the 2013 operational version of HWRF is used to analyze the POM-TC ocean temperature response in retrospective HWRF–POM-TC forecasts of Atlantic Hurricanes Earl (2010), Igor (2010), Irene (2011), Isaac (2012), and Leslie (2012) against remotely sensed and in situ SST and subsurface ocean temperature observations. The model generally underestimates the hurricane-induced upper-ocean cooling, particularly far from the storm track, as well as the upwelling and downwelling oscillation in the cold wake, compared with observations. Nonetheless, the timing of the model SST cooling is generally accurate (after accounting for along-track timing errors), and the ocean model’s vertical temperature structure is generally in good agreement with observed temperature profiles from airborne expendable bathythermographs.

Tropical cyclones are fueled by the air–sea heat flux, which is reduced when the ocean surface cools due to mixed layer deepening and upwelling. Wave-driven Langmuir turbulence can significantly modify these processes. This study investigates the impact of sea-state-dependent Langmuir turbulence on the three-dimensional ocean response to a tropical cyclone in coupled wave–ocean simulations. The Stokes drift is computed from the simulated wave spectrum using the WAVEWATCH III wave model and passed to the three-dimensional Princeton Ocean Model. The Langmuir turbulence impact is included in the vertical mixing of the ocean model by adding the Stokes drift to the shear of the vertical mean current and by including Langmuir turbulence enhancements to the K -profile parameterization (KPP) scheme. Results are assessed by comparing simulations with explicit (sea-state dependent) and implicit (independent of sea state) Langmuir turbulence parameterizations, as well as with turbulence driven by shear alone. The results demonstrate that the sea-state-dependent Langmuir turbulence parameterization significantly modifies the three-dimensional ocean response to a tropical cyclone. This is due to the reduction of upwelling and horizontal advection where the near-surface currents are reduced by Langmuir turbulence. The implicit scheme not only misses the impact of sea-state dependence on the surface cooling, but it also misrepresents the impact of the Langmuir turbulence on the Eulerian advection. This suggests that explicitly resolving the sea-state-dependent Langmuir turbulence will lead to increased accuracy in predicting the ocean response in coupled tropical cyclone–ocean models.