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Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Summary: The performance of an array of donor‐acceptor based bulk heterojunction (BHJ) polymer solar cells (PSC) containing indoloindole as a key donor block with varying degrees of fluorinated benzothiadiazole (BT) as an acceptor block is reported. Fluorination of BT can enhance crystallinity and planarity of the polymer backbone due to intramolecular F‐S interactions. This also leads to deeper highest occupied molecular orbital (HOMO) energy levels leading to high JSC and VOC. The PSC properties of this series of new copolymer donors blended with fullerene acceptors show a homogeneous and uniform fibrous network in the blend film. The most homogeneous film was achieved with monofluorinated BT (PFDHI‐TFT) that resulted in better charge extraction pathway leading to high power conversion efficiency (PCE). The solar cell using PFDHI‐TFT as donor and fullerene acceptor showed PCE of 5.98% with VOC of 0.80 V, JSC of 10.56 mA cm−2, and fill factor (FF) of 0.71, respectively, under AM 1.5G illumination (100 mW cm−2) in the absence of annealing. [ABSTRACT FROM AUTHOR]

A fused pyrrolopyridine core having substituents on the nitrogen atom instead of the carbon atom of the indoloindole unit is developed as a new donor unit for organic electronics. The new donor–acceptor copolymers, PDHPHBT, PDHPFBT, and PDHP2FBT, are synthesized using the new donor unit, well‐known benzothiadiazole derivatives containing fluorine atoms as the acceptor. The thermal, optical, and electrochemical properties of these novel copolymers are reported. A solar cell using PDHPFBT with diphenyl ether has an open‐circuit voltage, short‐circuit current, fill factor, and power conversion efficiency of 0.86 V, 11.32 mA cm‐2, 0.59%, and 5.68%, respectively, under AM 1.5G illumination (100 mW cm‐2) in the absence of annealing. A novel building block, a fused pyrrolo[2,3‐b]pyridine, is developed for various organic electronics applications. The nitrogen atom instead of carbon atom of the indoloindole moiety has the advantages of decreased band‐gap and deep highest‐occupied molecular orbital level. [ABSTRACT FROM AUTHOR]

Melanoma is the most serious type of skin cancer and remains highly drug-resistant. Therefore, the discovery of novel effective agents against melanoma is in high demand. Herein, we investigated the cytotoxic activities in melanoma cells and underlying molecular mechanisms of beauvericin (BEA) and its analogue beauvericin G 1 (BEA G 1 ), which are cyclohexadepsipeptides isolated from fungi. BEA and BEA G 1 significantly suppressed the growth, clonogenicity, migration, and invasion of A375SM human melanoma cells and promoted caspase-dependent apoptosis through upregulation of death receptors, as well as modulation of pro- and anti-apoptotic Bcl-2 family members. Furthermore, the effects of BEA and BEA G 1 were associated with the suppression of multiple molecular targets that play crucial roles in melanoma oncogenesis, including ERK, JNK, p38, NF-κB, STAT3, and MITF. Notably, the cytotoxic efficacy of BEA G 1 against A375SM cells was stronger than that of BEA. These findings suggest that BEA and BEA G 1 can be further investigated as potent cytotoxic natural compounds for the suppression of melanoma progression.

Glioblastoma multiforme (GBM) is the most aggressive and common type of human primary brain tumor. Glioblastoma stem-like cells (GSCs) have been proposed to contribute to tumor initiation, progression, recurrence, and therapeutic resistance of GBM. Therefore, targeting GSCs could be a promising strategy to treat this refractory cancer. Calmodulin (CaM), a major regulator of Ca 2+ -dependent signaling, controls various cellular functions via interaction with multiple target proteins. Here, we investigated the anticancer effect of hydrazinobenzoylcurcumin (HBC), a Ca 2+ /CaM antagonist, against GSCs derived from U87MG and U373MG cells. HBC significantly inhibited not only the self-renewal capacity, such as cell growth and neurosphere formation but also the metastasis-promoting ability, such as migration and invasion of GSCs. HBC induced apoptosis of GSCs in a caspase-dependent manner. Notably, HBC repressed the phosphorylation of Ca 2+ /CaM-dependent protein kinase II (CaMKII), c-Met, and its downstream signal transduction mediators, thereby reducing the expression levels of GSC markers, such as CD133, Nanog, Sox2, and Oct4. In addition, the knockdown of CaMKIIγ remarkably decreased the cancer stem cell-like phenotypes as well as the expression of stemness markers by blocking c-Met signaling pathway in U87MG GSCs. These results suggest that HBC suppresses the stem-like features of GBM cells via downregulation of CaM/CaMKII/c-Met axis and therefore CaMKII may be a novel therapeutic target to eliminate GSCs., (© 2018 Wiley Periodicals, Inc.)