Current Medicinal Chemistry - Volume 29, Issue 39, 2022

Photoacoustic imaging (PAI) is a non-invasive modality for molecular imaging and is on the way to becoming a routine clinical diagnostic tool. The advantage of PAI over many other currently used modalities is its ability to potentially image in vivo a variety of enzymatic and physiological processes as well as metabolites in real time at high tissue depths. For this purpose, photoacoustic signal generating chromophores, which have the ability to change their signal characteristics upon reaction, to their environments or trapping reactive species, are important. This review article provides an overview of the concepts for activatable small molecule probes for photoacoustic imaging, highlights the requirements for structural and optical properties, and describes their responses to the selective triggers.

Background: Non-small cell lung cancer (NSCLC) is a deadly disease that affects millions globally and its treatment includes surgery, chemotherapy, and radiotherapy. Chemotherapy and radiotherapy have many disadvantages, which include potential harmful side effects. Due to the widespread use of drugs in lung cancer, drug treatment becomes challenging due to multidrug resistance and adverse reactions. According to the recent findings, natural products (NPs) and their derivatives are being used to inhibit and suppress cancer cells. Objective: Our objective is to highlight the importance of phytochemicals for treating NSCLC by focusing on the structural features essential for the desired activity with fewer side effects compared to synthetic molecules. Methods: This review incorporated data from the most recent literature, including in vitro, in vivo, nanoformulation-based recent advancements, and clinical trials, as well as the structure-activity relationship (SAR), described for a variety of possible natural bioactive molecules in the treatment of NSCLC. Results: The analysis of data from recent in vitro, in vivo studies and ongoing clinical trials are highlighted. The SAR studies of potential NPs signify the presence of several common structural features that can be used to guide future drug design and development. Conclusion: The role of NPs in the battle against NSCLC can be effective, as evidenced by their structural diversity and affinity toward various molecular targets. The main purpose of the review is to gather information about NPs used in the treatment of NSCLC.

Brain diseases, including Alzheimer's disease (AD), brain tumors and Parkinson's disease (PD), pose heavy pressure on the public healthcare system. The main obstacle to vanquish brain diseases is the blood-brain barrier (BBB), which is a selective barrier mainly formed by brain endothelial cells. BBB prevents almost all drugs from reaching the brain, thereby hindering drug delivery. Over the past few decades, considerable signs of progress have been made in crossing the BBB and treating brain diseases. Gold nanoparticles (AuNPs) demonstrate the characteristics of adjustable size, unique optical properties, flexible surface modification, and good biocompatibility, which all contribute AuNPs as a promising candidate in biomedical fields. This article reviews the structure and properties of BBB, and discusses main transport routes through the BBB. Besides, nanoparticles, specially AuNPs applied in brain diseases as main drug delivery platforms, are systematically summarized, emphasizing several methods to modify AuNPs, including tuning particle size and surface modification, which are aimed at promoting BBB penetration or prolonging circulation time of AuNPs. In addition, AuNPs utilized in brain diseases are introduced in detail from the aspects of brain imaging, AD, brain tumors, and PD. Prospects and challenges that need to be considered in further investigations and clinical transformation of AuNPs used in brain diseases are also included, hoping to bring new insights into the applications of AuNPs in brain diseases.

Objective: This research sought to explore the effect and mechanism of long non-coding RNA SNHG16 on esophageal cancer (EC) cell proliferation and self-renewal. Methods: SNHG16 expression was measured in EC9706 and KYSE150 cells. EC9706 and KYSE150 cells were transfected with Lenti-SNHG16, sh-SNHG16, Lenti-protein patched homolog 1 (PTCH1), miR-802 mimic, or miR-802 inhibitor. Flow cytometry was used to sort cancer stem cells (CSCs) in EC9706 and KYSE150 cells. Cell proliferation in EC cells was measured, in addition to colony and tumorsphere numbers. The possible interactions among SNHG16, PTCH1, and miR-802 were identified by dual luciferase reporter and RNA pull-down assays. The expression of the genes in the Hedgehog pathway was detected. Nude mice were injected with SNHG16-silenced EC9706 cells to observe the tumorigenicity of EC9706 cells. Results: Upregulated SNHG16 expression was found in CSCs, whose expression was decreased during the differentiation of CSCs. SNHG16 or PTCH1 overexpression or miR-802 inhibition promoted the proliferation, colony formation, and tumorsphere formation of EC9706 and KYSE150 cells as well as SOX2, OCT4, Bmi-1, and PTCH1 expression. Consistently, SNHG16 knockdown or miR-802 overexpression inhibited EC progression. Moreover, SNHG16 and PTCH1 were competitively bound to miR-802, and SNHG16 orchestrated the miR-802/PTCH1 axis to activate the Hedgehog pathway. SNHG16 silencing repressed the tumorigenicity of EC9706 in nude mice. Conclusion: Conclusively, SNHG16 acts as a sponge of miR-802 to upregulate PTCH1 and activate the Hedgehog pathway, thus promoting EC cell proliferation and selfrenewal.

Background: Barbaloin, found in Aloe vera, exerts broad pharmacological activities, including antioxidant, anti-inflammatory, and anti-cancer. This study aims to investigate the effects of barbaloin on the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Methods: Osteogenic induction of hBMSCs was performed in the presence or absence of barbaloin. Cell viability was determined by using the CCK-8 assay. The characteristic of hBMSCs was identified by using flow cytometry. Intracellular alkaline phosphatase (ALP) staining was performed to evaluate the ALP activity in hBMSCs. Alizarin Red S staining was performed to evaluate the matrix mineralization. The mRNA and protein levels of target genes were determined using qRT-PCR and western blotting, respectively. Results: Treatment with barbaloin (10 and 20 μg/mL) significantly increased cell viability of hBMSCs after 72 hours. In addition, treatment with barbaloin increased the mRNA expression levels of ALP and its activities. Treatment with barbaloin also increased matrix mineralization and the mRNA and protein levels of late-differentiated osteoblast marker genes BMP2, RUNX2, and SP7 in hBMSCs. The underlying mechanisms revealed that barbaloin increased the protein expressions of Wnt/β-catenin pathway-related biomarkers. Conclusion: Barbaloin promotes osteogenic differentiation of hBMSCs by the regulation of the Wnt/β-catenin signaling pathway.