SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer.

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors.

Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs.

Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen.

We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β and targeted to T cells induced polyclonal T regulatory cells (Tregs) that protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses to tolerogenic ones. Using C57BL/6 mice and BALB/c mice as either donors or recipients of allogeneic splenocytes, we found that treatment with the tolerogenic NPs in both strains of mice resulted in a marked inhibition of mixed lymphocyte reaction (MLR) to donor cell alloantigen but not to third-party control mouse cells after transfer of the allogeneic cells.

Exosomes in diagnostic and therapeutic applications of ovarian cancer.

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need.

Harnessing small extracellular vesicles for pro-oxidant delivery: novel approach for drug-sensitive and resistant cancer therapy.

Multidrug resistance (MDR) is an inevitable clinical problem in chemotherapy due to the activation of abundant P-glycoprotein (P-gp) that can efflux drugs. Limitations of current cancer therapy highlight the need for the development of a comprehensive cancer treatment strategy, including drug-resistant cancers. Small extracellular vesicles (sEVs) possess significant potential in surmounting drug resistance as they can effectively evade the efflux mechanism and transport small molecules directly to MDR cancer cells.

Gut Dysbiosis: A New Avenue for Stroke Prevention and Therapeutics.

A stroke is a serious life-threatening condition and a leading cause of death and disability that happens when the blood vessels to part of the brain are blocked or burst. While major advances in the understanding of the ischemic cascade in stroke was made over several decades, limited therapeutic options and high mortality and disability have caused researchers to extend the focus toward peripheral changes beyond brain. The largest proportion of microbes in human body reside in the gut and the interaction between host and microbiota in health and disease is well known.

Differential responses to double-stranded RNA injection and feeding in Mormon cricket (Orthoptera: Tettigoniidae).

The Mormon cricket, Anabrus simplex, is a flightless katydid, one of the major devastating rangeland pests in several states of the western United States. During the past few years, their sudden and periodic outbreaks into massive migratory bands caused significant economic losses to the rangeland forage and agricultural crops, particularly grain crops. Current population management methods rely heavily on broad-spectrum chemical insecticides, which could be toxic to nontargets, and even the targeted species might develop resistance in the long run.

Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed in biomedical fields, including targeted delivery of antitumor therapy. Conventional magnetic tumor targeting has used simple static magnetic fields (SMFs), which cause SPIONs to linearly aggregate into a long chain-like shape. Such agglomeration greatly hinders the intracellular targeting of SPIONs into tumors, thus reducing the therapeutic efficacy.

Understanding of Ovarian Cancer Cell-Derived Exosome Tropism for Future Therapeutic Applications.

Exosomes, a subtype of extracellular vesicles, ranging from 50 to 200 nm in diameter, and mediate cell-to-cell communication in normal biological and pathological processes. Exosomes derived from tumors have multiple functions in cancer progression, resistance, and metastasis through cancer exosome-derived tropism. However, there is no quantitative information on cancer exosome-derived tropism.

Tumor-targeted exosomes for delivery of anticancer drugs.

Exosomes are small phospholipid bilayer vesicles that are naturally produced by all living cells, both prokaryotes and eukaryotes. The exosomes due to their unique size, reduced immunogenicity, and their ability to mimic synthetic liposomes in carrying various anticancer drugs have been tested as drug delivery vehicles for cancer treatment. An added advantage of developing exosomes as a drug carrier is the ease of manipulating their intraluminal content and their surface modification to achieve tumor-targeted drug delivery.

Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.

Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles.

Immunogenicity and Durability of Antibody Responses to Homologous and Heterologous Vaccinations with BNT162b2 and ChAdOx1 Vaccines for COVID-19.

During the COVID-19 pandemic, vaccines were developed based on various platform technologies and were approved for emergency use. However, the comparative analysis of immunogenicity and durability of vaccine-induced antibody responses depending on vaccine platforms or vaccination regimens has not been thoroughly examined for mRNA- or viral vector-based vaccines. In this study, we assessed spike-binding IgG levels and neutralizing capacity in 66 vaccinated individuals prime-boost immunized either by homologous (BNT162b2-BNT162b2 or ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) vaccination for six months after the first vaccination.

Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry.

The influenza A virus (IAV) has caused several pandemics, and therefore there are many ongoing efforts to identify novel antiviral therapeutic strategies including vaccines and antiviral drugs. However, influenza viruses continuously undergo antigenic drift and shift, resulting in the emergence of mutated viruses. In turn, this decreases the efficiency of existing vaccines and antiviral drugs to control IAV infection.

Multi-target cell therapy using a magnetoelectric microscale biorobot for targeted delivery and selective differentiation of SH-SY5Y cells magnetically driven cell stamping.

Cell therapy refers to a treatment that involves the delivery of cells or cellular material by means of injection, grafting, or implantation in order to replace damaged tissue and restore its function, or to aid the body in fighting disease. However, limitations include poor targeting delivery and low therapeutic efficacy due to low cell survival. Hence, novel approaches are required to increase cell delivery efficiency and enhance therapeutic efficacy selective cell differentiation at target areas.

Intraocular RGD-Engineered Exosomes and Active Targeting of Choroidal Neovascularization (CNV).

Purpose: To assess the transretinal penetration of intravitreally injected retinal multicell-derived exosomes and to develop exosome-based active targeting of choroidal neovascularization (CNV) by bioengineering with ASL, which is composed of a membrane Anchor (BODIPY), Spacer (PEG), and targeting Ligands (cyclic RGD peptide).

Methods: Retinal multicell-derived exosomes were recovered from a whole mouse retina using differential ultracentrifugation. Their size, number, and morphology were characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM).

Pseudo-Isolated α-Helix Platform for the Recognition of Deep and Narrow Targets.

Although interest in stabilized α-helical peptides as next-generation therapeutics for modulating biomolecular interfaces is increasing, peptides have limited functionality and stability due to their small size. In comparison, α-helical ligands based on proteins can make steric clash with targets due to their large size. Here, we report the design of a monomeric pseudo-isolated α-helix (mPIH) system in which proteins behave as if they are peptides.

Unique behaviour of the α-helix in bending deformation.

The maximum degree of bending that can be tolerated by the rigid rod-like α-helix remains unknown; however, it should be very difficult or even impossible to make α-helices with varying degrees of curvature in folded proteins. As an experimentally tractable model, here we utilize cyclic proteins and peptides to determine the maximum possible bending in the α-helix. We artificially enforced bending in the α-helices by using variously sized macrocycles and compared the structural characteristics of the macrocycles with those of their linear counterparts.

Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy.

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases.

A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice.

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice.

P=O Functionalized Black Phosphorus/1T-WS Nanocomposite High Efficiency Hybrid Photocatalyst for Air/Water Pollutant Degradation.

Research on layered two-dimensional (2D) materials is at the forefront of material science. Because 2D materialshave variousplate shapes, there is a great deal of research on the layer-by-layer-type junction structure. In this study, we designed a composite catalyst with a dimension lower than two dimensions and with catalysts that canbe combined so that the band structures can be designed to suit various applications and cover for each other's disadvantages.

A Benzenesulfonamide-Based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in the abdominal cavity through dissemination in the peritoneal fluid and ascites, efficiently adapt to the nutrient-deprived microenvironment, and resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation is critical for the adaptation of EOC cells to this otherwise hostile microenvironment.

Metabolic and immunomodulatory control of type 1 diabetes via orally delivered bile-acid-polymer nanocarriers of insulin or rapamycin.

Oral formulations of insulin are typically designed to improve its intestinal absorption and increase its blood bioavailability. Here we show that polymerized ursodeoxycholic acid, selected from a panel of bile-acid polymers and formulated into nanoparticles for the oral delivery of insulin, restored blood-glucose levels in mice and pigs with established type 1 diabetes. The nanoparticles functioned as a protective insulin carrier and as a high-avidity bile-acid-receptor agonist, increased the intestinal absorption of insulin, polarized intestinal macrophages towards the M2 phenotype, and preferentially accumulated in the pancreas of the mice, binding to the islet-cell bile-acid membrane receptor TGR5 with high avidity and activating the secretion of glucagon-like peptide and of endogenous insulin.

Magnetically Actuated Drug Delivery Helical Microrobot with Magnetic Nanoparticle Retrieval Ability.

Therapeutic drug delivery microrobots capable of accurate targeting using an electromagnetic actuation (EMA) system are being developed. However, these drug delivery microrobots include a large number of magnetic nanoparticles (MNPs) for accurate EMA targeting, which causes side effects, such as problems with membrane integrity and normal cell apoptosis. Here, a biocompatible and hydrolyzable PEGDA-based drug delivery helical microrobot capable of MNP retrieval is proposed in which doxorubicin (DOX), an anticancer drug, is encapsulated and MNPs are conjugated by a disulfide bond.