The Renoprotective and Anti-Inflammatory Effects of Human Urine-Derived Stem Cells on Acute Kidney Injury Animals.

BACKGROUND: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. METHODS: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. RESULTS: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. CONCLUSION: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI.

Mathematical modeling and application of IL-1ß/TNF signaling pathway in regulating chondrocyte apoptosis.

Introduction: Mathematical model can be used to model complex biological processes, and have shown potential in describing apoptosis in chondrocytes. Method: In order to investigate the regulatory mechanisms of TNF signaling pathway in regulating chondrocyte apoptosis, a fractional-order differential equation model is proposed to describe the dynamic behavior and mutual interaction of apoptosis-related genes under the activation of TNF signaling pathway. Compared with the traditional molecular biology techniques, the proposed mathematical modeling has advantages to providing a more comprehensive understanding of the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis. Result: In this paper, differentially expressed genes induced by IL-1ß in human chondrocyte apoptosis are screened using high-throughput sequencing. It is found that they were significantly enriched in the TNF signaling pathway. Therefore, a mathematical model of the TNF signaling pathway is built. Using real-time PCR experiments, mRNA data is measured and used to identify the model parameters, as well as the correlation coefficient. Finally, the sensitivity of the model parameters is discussed by using numerical simulation methods, which can be used to predict the effects of different interventions and explore the optimal intervention strategies for regulating chondrocyte apoptosis. Discussion: Therefore, fractional-order differential equation modeling plays an important role in understanding the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis and its potential clinical applications.

One-step fabrication of cell sheet-laden hydrogel for accelerated wound healing.

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.

Dynamic photoelectrical regulation of ECM protein and cellular behaviors.

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions. This n-doping process stimulated the conformational switches of ECM proteins. The structural alterations in these ECM interactors significantly reduced the specificity of the cell surface receptor-ligand interaction (e.g., integrin recognition), leading to dynamic regulation of cell adhesion and eventual cell detachment. RNA-sequencing results revealed that the detached bone marrow mesenchymal stromal cell sheets from the Gr/Si system manifested regulated immunoregulatory properties and enhanced osteogenic differentiation, implying their potential application in bone tissue regeneration. This work not only provides a fast and feasible method for controllable cells/cell sheets harvesting but also gives new insights into the understanding of cell-ECM-material communications.

First assessment of thermoacoustic tomography for in vivo detection of rheumatoid arthritis in the finger joints detection of rheumatoid arthritis in the finger joints.

BACKGROUND: The diagnosis of rheumatoid arthritis (RA) is complicated because of the complexity of symptoms and joint structures. Current clinical imaging techniques for the diagnosis of RA have strengths and weaknesses. Emerging imaging techniques need to be developed for the diagnosis or auxiliary diagnosis of RA. PURPOSE: This study aimed to demonstrate the potential of thermoacoustic tomography (TAT) for in vivo detection of RA in the finger joints. METHODS: Finger joints were imaged by a TAT system using three different microwave illumination methods including pyramidal horn antenna, and parallel in-phase and anti-phase microwave illuminations. Both diseased and healthy joints were imaged and compared when the three microwave illumination methods were used. Magnetic resonance imaging (MRI) of all the joints was performed to validate the TAT findings. In addition, two diseased joints were imaged at two time points by the pyramidal horn antenna-based TAT to track/monitor the progression of RA during a time period of 16 months. Three-dimensional (3-D) TAT images of the joints were also obtained. RESULTS: The TAT images of the diseased joints displayed abnormalities in bone and soft tissues compared to the healthy ones. The TAT images by pyramidal horn antenna and in-phase microwave illumination showed high similarity in image appearance, while the anti-phase-based TAT images provided different information about the disease. We found that the TAT findings matched well with the MRI images. The 3-D TAT images effectively displayed the stereoscopic effect of joint lesions. Finally, it was evident that TAT could detect the development of the lesions in 16 months. CONCLUSION: TAT can noninvasively visualize bone lesions and soft tissue abnormalities in the joints with RA. This first in vivo assessment of TAT provides a foundation for its clinical application to the diagnosis and monitoring of RA in the finger joints.

Light-induced osteogenic differentiation of BMSCs with graphene/TiO2 composite coating on Ti implant.

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO2) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO2, a heterojunction formed at the interface of rGO and TiO2. With visible light illumination, positive charges accumulated on the surface of rGO/TiO2 film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.

Modeling the COVID-19 Epidemic With Multi-Population and Control Strategies in the United States.

As of January 19, 2021, the cumulative number of people infected with coronavirus disease-2019 (COVID-19) in the United States has reached 24,433,486, and the number is still rising. The outbreak of the COVID-19 epidemic has not only affected the development of the global economy but also seriously threatened the lives and health of human beings around the world. According to the transmission characteristics of COVID-19 in the population, this study established a theoretical differential equation mathematical model, estimated model parameters through epidemiological data, obtained accurate mathematical models, and adopted global sensitivity analysis methods to screen sensitive parameters that significantly affect the development of the epidemic. Based on the established precise mathematical model, we calculate the basic reproductive number of the epidemic, evaluate the transmission capacity of the COVID-19 epidemic, and predict the development trend of the epidemic. By analyzing the sensitivity of parameters and finding sensitive parameters, we can provide effective control strategies for epidemic prevention and control. After appropriate modifications, the model can also be used for mathematical modeling of epidemics in other countries or other infectious diseases.

The important roles of protein SUMOylation in the occurrence and development of leukemia and clinical implications.

Leukemia is a severe malignancy of the hematopoietic system, which is characterized by uncontrolled proliferation and dedifferentiation of immature hematopoietic precursor cells in the lymphatic system and bone marrow. Leukemia is caused by alterations of the genetic and epigenetic regulation of processes underlying hematologic malignancies, including SUMO modification (SUMOylation). Small ubiquitin-like modifier (SUMO) proteins covalently or noncovalently conjugate and modify a large number of target proteins via lysine residues. SUMOylation is a small ubiquitin-like modification that is catalyzed by the SUMO-specific activating enzyme E1, the binding enzyme E2, and the ligating enzyme E3. SUMO is covalently linked to substrate proteins to regulate the cellular localization of target proteins and the interaction of target proteins with other biological macromolecules. SUMOylation has emerged as a critical regulatory mechanism for subcellular localization, protein stability, protein-protein interactions, and biological function and thus regulates normal life activities. If the SUMOylation process of proteins is affected, it will cause a cellular reaction and ultimately lead to various diseases, including leukemia. There is growing evidence showing that a large number of proteins are SUMOylated and that SUMOylated proteins play an important role in the occurrence and development of various types of leukemia. Targeting the SUMOylation of proteins alone or in combination with current treatments might provide powerful targeted therapeutic strategies for the clinical treatment of leukemia.

The Critical Roles of the SUMO-Specific Protease SENP3 in Human Diseases and Clinical Implications.

Post-translational modification by SUMO (small ubiquitin-like modifier) proteins has been shown to regulate a variety of functions of proteins, including protein stability, chromatin organization, transcription, DNA repair, subcellular localization, protein-protein interactions, and protein homeostasis. SENP (sentrin/SUMO-specific protease) regulates precursor processing and deconjugation of SUMO to control cellular mechanisms. SENP3, which is one of the SENP family members, deconjugates target proteins to alter protein modification. The effect of modification via SUMO and SENP3 is crucial to maintain the balance of SUMOylation and guarantee normal protein function and cellular activities. SENP3 acts as an oxidative stress-responsive molecule under physiological conditions. Under pathological conditions, if the SUMOylation process of proteins is affected by variations in SENP3 levels, it will cause a cellular reaction and ultimately lead to abnormal cellular activities and the occurrence and development of human diseases, including cardiovascular diseases, neurological diseases, and various cancers. In this review, we summarized the most recent advances concerning the critical roles of SENP3 in normal physiological and pathological conditions as well as the potential clinical implications in various diseases. Targeting SENP3 alone or in combination with current therapies might provide powerful targeted therapeutic strategies for the treatment of these diseases.

Gr/TiO2 Films with Light-Controlled Positive/Negative Charge for Cell Harvesting Application.

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively. The highest cell detachment ratio reaches about 95%. The mechanism of such a cell detachment is contributed to light illumination generates charge accumulation, which, in turn, changes the conformation of the extracellular matrix protein molecules adsorbed to a more disordered state, and eventually leads to the cells detachment. Such UV and visible light responsive Gr/TiO2 film could be a good candidate for a surface with light-induced cell detachment property.

Graphene/Si-Promoted Osteogenic Differentiation of BMSCs through Light Illumination.

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.