Treatment with either estradiol or an estrogen receptor (ER)␣ ligand has been shown to be both antiinflammatory and neuroprotective in a variety of neurological disease models, but whether neuroprotective effects could be observed in the absence of an antiinflammatory effect has remained unknown. Here, we have contrasted effects of treatment with an ER␣ vs. an ER␤ ligand in experimental autoimmune encephalomyelitis, the multiple sclerosis model with a known pathogenic role for both inflammation and neurodegeneration. Clinically, ER␣ ligand treatment abrogated disease at the onset and throughout the disease course. In contrast, ER␤ ligand treatment had no effect at disease onset but promoted recovery during the chronic phase of the disease. ER␣ ligand treatment was antiinflammatory in the systemic immune system, whereas ER␤ ligand treatment was not. Also, ER␣ ligand treatment reduced CNS inflammation, whereas ER␤ ligand treatment did not. Interestingly, treatment with either the ER␣ or the ER␤ ligand was neuroprotective, as evidenced by reduced demyelination and preservation of axon numbers in white matter, as well as decreased neuronal abnormalities in gray matter. Thus, by using the ER␤ selective ligand, we have dissociated the antiinflammatory effect from the neuroprotective effect of estrogen treatment and have shown that neuroprotective effects of estrogen treatment do not necessarily depend on antiinflammatory properties. Together, these findings suggest that ER␤ ligand treatment should be explored as a potential neuroprotective strategy in multiple sclerosis and other neurodegenerative diseases, particularly because estrogen-related toxicities such as breast and uterine cancer are mediated through ER␣.experimental autoimmune encephalomyelitis ͉ neuroprotection ͉ multiple sclerosis selective estrogen receptor modulators

Consumer interest in cosmetic industry products that produce whitening effects has increased demand for agents that decrease melanin production. Many such anti-melanogenic agents are associated with side effects, such as contact dermatitis and high toxicity, and also exhibit poor skin penetration. Considerable recent research has focused on plant-derived products as alternatives to chemotherapeutic agents that possess fewer side effects. In the current study, we investigated the anti-melanogenic effects of extracellular vesicles (EVs) extracted from leaves and stems of Dendropanax morbifera.Using spectrophotometric and biochemical approaches, we found that leaf-derived extracellular vesicles (LEVs) and stem-derived extracellular vesicles (SEVs) reduced melanin content and tyrosinase (TYR) activity in the B16BL6 mouse melanoma cell line in a concentration-dependent manner. An electron microscopy analysis further confirmed that LEVs and SEVs induce a concentration-dependent decrease in melanin content in melanoma cells. Both LEVs and SEVs exerted a greater whitening effect on m e l a n o m ac e l l st h a na r b u t i n ,u s e da sap o s i t i v ec o ntrol, with LEVs producing the greater effect. Notably, neither LEVs nor SEVs induced significant cytotoxicity. We also examined the effects of plantderived EVs on the expression of tyrosinase-relatedp r o t e i n s(T R P s)i nm e l a n o m ac e l l s .L E V si n h i b i t e d expression of melanogenesis-related genes and proteins, including microphthalmia-associated transcription factor (MITF), TYR, TRP-1 and TRP-2. In a human epidermis model, LEVs exerted a stronger inhibitory effect on melanin production than arbutin. Collectively, our data suggest that LEVs from D. morbifera may be a novel candidate natural substance for use as an anti-melanogenic agent in cosmeceutical formulations.

Edible plants have been widely used in traditional therapeutics because of the biological activities of their natural ingredients, including anticancer, antioxidant, and anti-inflammatory properties. Plant sap contains such medicinal substances and their secondary metabolites provide unique chemical structures that contribute to their therapeutic efficacy. Plant extracts are known to contain a variety of extracellular vesicles (EVs) but the effects of such EVs on various cancers have not been investigated. Here, we extracted EVs from four plants—Dendropanax morbifera, Pinus densiflora, Thuja occidentalis, and Chamaecyparis obtusa—that are known to have cytotoxic effects. We evaluated the cytotoxic effects of these EVs by assessing their ability to selectively reduce the viability of various tumor cell types compared with normal cells and low metastatic cells. EVs from D. morbifera and P. densiflora sap showed strong cytotoxic effects on tumor cells, whereas those from T. occidentalis and C. obtusa had no significant effect on any tumor cell types. We also identified synergistic effect of EVs from D. morbifera and P. densiflora saps on breast and skin tumor cells and established optimized treatment concentrations. Our findings suggest these EVs from plant sap as new candidates for cancer treatment.

Size-based filtration techniques have been developed for high-throughput isolation of extracellular vesicles (EVs). Conventional direct filtration systems have limitations in that large particles generally not only block the pores of the membrane but also damage the particles because of the high fluid pressure. Here, we propose a cyclic tangential flow filtration (TFF) system that includes two membranes with pore sizes of 200 and 30 nm, connected to a peristaltic pump that feeds the stream flowing to the membrane for continuous circulation. The cyclic TFF system is better able to isolate the specific 30–200 nm size range in one step through dual cyclic filtration compared with direct filtration (DF) and single cyclic TFF (scTFF). We further introduced a buffer-exchange process to the dcTFF system after filtration to remove contaminants for more efficient purification. As a result of comparative evaluation of dcTFF and ExoQuick, EVs isolated by dcTFF had more abundant exosome markers and active EVs. The cyclic TFF system not only has great potential to separate EVs with high selectivity and separation efficiency in small volumes of samples but can also be used in clinical applications, including medical diagnostic procedures.

Cancer-associated fibroblasts (CAFs) in the cancer microenvironment play an essential role in metastasis. Differentiation of endothelial cells into CAFs is induced by cancer cell-derived exosomes secreted from cancer cells that transfer molecular signals to surrounding cells. Differentiated CAFs facilitate migration of cancer cells to different regions through promoting extracellular matrix (ECM) modifications. However, in vitro models in which endothelial cells exposed to cancer cell-derived exosomes secreted from various cancer cell types differentiate into CAFs or a microenvironmentally controlled model for investigating cancer cell invasion by CAFs have not yet been studied. In this study, we propose a three-dimensional in vitro cancer cell invasion model for real-time monitoring of the process of forming a cancer invasion site through CAFs induced by exosomes isolated from three types of cancer cell lines. The invasiveness of cancer cells with CAFs induced by cancer cell-derived exosomes (eCAFs) was significantly higher than that of CAFs induced by cancer cells (cCAFs) through physiological and genetic manner. In addition, different genetic tendencies of the invasion process were observed in the process of invading cancer cells according to CAFs. Our 3D microfluidic platform helps to identify specific interactions among multiple factors within the cancer microenvironment and provides a model for cancer drug development.

RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP).

BACKGROUND: Plastics that are used in our daily lives largely end up in the environment. In agricultural environments, plastic wastes and microplastics can be found due to the uses and improper management of plastic products (e.g., vinyl greenhouses and mulching vinyl). Microplastics can also interact with contaminants in the agricultural environment. Therefore, this study was set to investigate the sorption characteristics of tetracycline, one of widely used antibiotics, on microplastics. METHODS AND RESULTS: The sorption tests were carried out with the tetracycline solutions (0-30 mg L -1 ) and microplastic films prepared from low density polyethylene (LDPE) and polyvinyl chloride (PVC). The residual tetracycline concentrations were analyzed and fitted to the Freundlich and Langmuir isotherm models. The tetracycline sorption patterns on LDPE and PVC films were described better with the Freundlich isotherm model than the Langmuir isotherm model. The isotherm model parameters suggested that the maximum sorption amount of tetracyline was greater for PVC, while the sorption affinity was greater for LDPE. CONCLUSION(S):Different types of microplastics can have different sorption characteristics of tetracycline. Therefore, there is a need for continuous research on the interaction of various types and shapes of microplastics and contaminants in the environment.

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