Transcriptional Factors Mediated Reprogramming to Pluripotency.

A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor 4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming mechanisms are still poorly understood medically. This technique has dramatically improved performance and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine. Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds, impacts kinetics, quality, and efficiency in stem cell research.

Nanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases.

Infectious diseases, particularly life-threatening pathogens such as small pox and influenza, have substantial implications on public health and global economies. Vaccination is a key approach to combat existing and emerging pathogens. Immunological memory is an essential characteristic used to evaluate vaccine efficacy and durability and the basis for the long-term effects of vaccines in protecting against future infections; however, optimizing the potency, improving the quality, and enhancing the durability of immune responses remains challenging and a focus for research involving investigation of nanovaccine technologies. In this review, we describe how nanovaccines can address the challenges for conventional vaccines in stimulating adaptive immune memory responses to protect against reinfection. We discuss protein and nonprotein nanoparticles as useful antigen platforms, including those with highly ordered and repetitive antigen array presentation to enhance immunogenicity through cross-linking with multiple B cell receptors, and with a focus on antigen properties. In addition, we describe how nanoadjuvants can improve immune responses by providing enhanced access to lymph nodes, lymphnode targeting, germinal center retention, and long-lasting immune response generation. Nanotechnology has the advantage to facilitate vaccine induction of long-lasting immunity against infectious diseases, now and in the future.

Physical Stimulation Combined with Biomaterials Promotes Peripheral Nerve Injury Repair.

Peripheral nerve injury (PNI) is a clinical problem with high morbidity that can cause severe damage. Surgical suturing or implants are usually required due to the slow speed and numerous factors affecting repair after PNI. An autologous nerve graft is the gold standard for PNI repair among implants. However, there is a potential problem of the functional loss of the donor site. Therefore, tissue-engineered nerve biomaterials are often used to bridge the gap between nerve defects, but the therapeutic effect is insufficient. In order to enhance the repair effect of nerve biomaterials for PNI, researchers are seeking to combine various stimulation elements, such as the addition of biological factors such as nerve growth factors or physical factors such as internal microstructural modifications of catheters and their combined application with physical stimulation therapy. Physical stimulation therapy is safer, is more convenient, and has more practical features than other additive factors. Its feasibility and convenience, when combined with nerve biomaterials, provide broader application prospects for PNI repair, and has therefore become a research hot spot. This paper will review the combined application of physical stimulation and biomaterials in PNI repair in recent years to provide new therapeutic ideas for the future use of physical stimulation in PNI repair.

Mechanisms Affecting Physical Aging and Swelling by Blending an Amphiphilic Component.

Polymer blending is a promising method to overcome stability obstacles induced by physical aging and swelling of implant scaffolds prepared from amorphous polymers in biomedical application, since it will not bring potential toxicity compared with chemical modification. However, the mechanism of polymer blending still remains unclearly explained in existing studies that fail to provide theoretical references in material R&D processes for stability improvement of the scaffold during ethylene oxide (EtO) sterilization, long-term storage, and clinical application. In this study, amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PELA) was blended with amorphous poly(lactic-co-glycolic acid) (PLGA) because of its good miscibility so as to adjust the glass transition temperature (Tg) and hydrophilicity of electrospun PLGA membranes. By characterizing the morphological stability and mechanical performance, the chain movement and the glass transition behavior of the polymer during the physical aging and swelling process were studied. This study revealed the modification mechanism of polymer blending at the molecular chain level, which will contribute to stability improvement and performance adjustment of implant scaffolds in biomedical application.

The interplay between mitochondria and store-operated Ca2+ entry: Emerging insights into cardiac diseases.

Store-operated Ca2+ entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria-endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca2+ signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.