Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

Drug Evaluation, Preclinical ; methods ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Protein Binding ; drug effects ; Small Molecule Libraries ; chemistry ; pharmacology ; Transcription Factors ; metabolism ; Tumor Suppressor Proteins ; metabolism

The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention.
AIDS Vaccines ; immunology ; therapeutic use ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Neutralizing ; immunology ; therapeutic use ; Genetic Therapy ; HIV Infections ; drug therapy ; prevention & control ; HIV-1 ; drug effects ; immunology ; physiology ; Humans ; Peptides ; chemistry ; immunology ; Small Molecule Libraries ; chemistry ; pharmacology ; therapeutic use ; Virus Internalization ; drug effects

Identification of the cellular targets of bioactive compounds is a major challenge and a key issue in chemical biology and drug discovery. As an important technology in functional proteomics, small molecule probes play a pivotal role in the identification of cellular targets of bioactive compounds. This review is intended to introduce the application principles and structural design philosophy of chemical probes for the purpose of mechanistic study. Recent cases of successful application were also discussed to further demonstrate the principles and significance ofbioactive small molecule-based probes.
Biotin ; metabolism ; Drug Delivery Systems ; Drug Design ; Drug Discovery ; methods ; Molecular Probe Techniques ; Molecular Probes ; chemistry ; Photoaffinity Labels ; Proteins ; metabolism ; Proteome ; chemistry ; Proteomics ; methods ; Small Molecule Libraries ; chemistry ; pharmacology

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement. Microfracture, an articular cartilage repair surgical technique, has been commonly used in the clinic to induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have also been used as cell therapy to repair degenerated cartilage. However, the therapeutic outcomes of all these techniques vary in different patients depending on their age, health, lesion size and the extent of damage to the cartilage. The repairing tissues either form fibrocartilage or go into a hypertrophic stage, both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage. One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. The recent development of human induced pluripotent stem cell (iPSCs), which are able to self-renew and differentiate into multiple cell types, provides a potentially valuable cell resource for drug screening in a "more relevant" cell type. Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.
Cell Differentiation ; drug effects ; Chondrocytes ; cytology ; drug effects ; metabolism ; Chondrogenesis ; drug effects ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; metabolism ; Keratinocytes ; cytology ; drug effects ; metabolism ; Luciferases ; genetics ; Peptides ; chemical synthesis ; metabolism ; Reproducibility of Results ; Small Molecule Libraries ; pharmacology

With the development of stem cells and regenerative medicine (treatment of various diseases using stem cells) research, the induction of differentiation of human stem cell technology has also made significant progress. The development of chemical biology offers a variety of small biological molecules for stem cell biology. This review focuses on how small molecule compounds (natural and synthetic) induce differentiation of stem cells.
Animals ; Cell Differentiation ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Embryonic Stem Cells ; cytology ; High-Throughput Screening Assays ; methods ; Humans ; Plants, Medicinal ; chemistry ; Regenerative Medicine ; trends ; Signal Transduction ; Small Molecule Libraries ; chemistry ; pharmacology ; Stem Cells ; cytology ; Wnt Proteins ; metabolism

Circular dichroism (CD) is an useful technique for monitoring DNA conformation changes resulting from changes in environmental conditions, such as temperature, ionic strength, and pH, and also for the study of the interaction between DNA and ligands (including small molecules and proteins). CD spectroscopy of DNA arises from the asymmetric backbone sugars and by the helical structures often adopted by nucleic acids. By the interpretation of induced circular dichroism (ICD) of ligand signals resulting from the coupling of electric transition moments of the ligand, DNA bases within the asymmetric DNA environment, ligand-DNA interactions, as well as the DNA-binding mode can be assessed. A number of important conclusions have been reported that related to the observed ICD signals resulting from the interactions between intercalators and groove binders with DNA. If short oligonucleotide sequences are used in the study, sequences-specific of binding also can be deduced. CD determination requires smaller amounts of sample, and not limited by the molecular weight or size and can be performed rapidly; though CD is of low resolution, but it's a complement to NMR and X-ray diffraction methods. This review will introduce the characters of the CD spectra of DNA, and its application to the studies of DNA with small molecules; some progress of the studies in our laboratory will also be discussed. CD is expected to be used as a screening method in seeking more DNA-targeted drugs, such as, antineoplastic, antimicrobial and antiviral drugs.
Animals ; Antineoplastic Agents ; chemistry ; Base Sequence ; Circular Dichroism ; methods ; DNA ; chemistry ; metabolism ; Humans ; Intercalating Agents ; chemistry ; Ligands ; Protein Binding ; Small Molecule Libraries ; pharmacology