Derivative Technologies of Expansion Microscopy and Applications in Biomedicine.

Expansion microscopy (ExM) is an innovative super-resolution imaging technique that utilizes physical expansion to magnify biological samples, facilitating the visualization of cellular structures that are challenging to observe using traditional optical microscopes. The fundamental principle of ExM revolves around employing a specialized hydrogel to uniformly expand biological samples, thereby achieving super-resolution imaging under conventional optical imaging conditions. This technology finds application not only in various biological samples such as cells and tissue sections, but also enables super-resolution imaging of large biological molecules including proteins, nucleic acids, and metabolite molecules.

Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.

Background: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD).

Objective: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice.

Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma.

The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy.

NIR-II Fluorescent Nanotheranostics with a Switchable Irradiation Mode for Immunogenic Sonodynamic Therapy.

Nanotheranostics, which integrate diagnostic and therapeutic functionalities, offer significant potential for tumor treatment. However, current nanotheranostic systems typically involve multiple molecules, each providing a singular diagnostic or therapeutic function, leading to challenges such as complex structural composition, poor targeting efficiency, lack of spatiotemporal control, and dependence on a single therapeutic modality. This study introduces NP, a nanoparticle functionalized with surface-bound cRGD for targeted delivery to αβ/αβ receptors on tumor cells, achieving theranostic integration by sequentially switching its irradiation modes.

Visualizing DNA/RNA, Proteins, and Small Molecule Metabolites within Live Cells.

Live cell imaging is essential for obtaining spatial and temporal insights into dynamic molecular events within heterogeneous individual cells, in situ intracellular networks, and in vivo organisms. Molecular tracking in live cells is also a critical and general requirement for studying dynamic physiological processes in cell biology, cancer, developmental biology, and neuroscience. Alongside this context, this review provides a comprehensive overview of recent research progress in live-cell imaging of RNAs, DNAs, proteins, and small-molecule metabolites, as well as their applications in molecular diagnosis, immunodiagnosis, and biochemical diagnosis.

Near Infrared-Fluorescent Dinuclear Iridium(III) Nanoparticles for Immunogenic Sonodynamic Therapy.

Dinuclear iridium(III) complexes activated by light-inducible spatiotemporal control are emerging as promising candidates for cancer therapy. However, broader applications of current light-activated dinuclear iridium(III) complexes are limited by the ineffective tissue penetration and undesirable feedback on guidance activation. Here, an ultrasound (US) triggered near infrared-fluorescent dinuclear iridium(III) nanoparticle, NanoIr, is first reported to precisely and spatiotemporally inhibit tumor growth.

Nanoparticles destabilizing the cell membranes triggered by NIR light for cancer imaging and photo-immunotherapy.

Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (P) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (P).

Localization of Cancer Cells for Subsequent Robust Photodynamic Therapy by ROS Responsive Polymeric Nanoparticles With Anti-Metastasis Complexes NAMI-A.

Photodynamic therapy (PDT), as a new type of light-mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non-resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen-dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed.

ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function.

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents.

Bioorthogonal Guided Activation of cGAS-STING by AIE Photosensitizer Nanoparticles for Targeted Tumor Therapy and Imaging.

Photodynamic therapy (PDT) and photothermal therapy (PTT) leverage reactive oxygen species (ROS) and control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria and nucleus, activating the cGAS-STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered by limitations such as suboptimal tumor targeting, aggregation-caused quenching (ACQ), and restricted excitation and emission wavelengths. Here, this work designs novel nanoparticles based on aggregation-induced emission (AIE) photosensitizer (BODTPE) for targeted tumor therapy and near-infrared II fluorescence imaging (NIR-II FLI) with enhanced PDT/PTT effects.

NIR-II Light Accelerated Prodrug Reduction of Pt(IV)-Incorporating Pseudo Semiconducting Polymers for Robust Degradation and Maximized Photothermal/Chemo-Immunotherapy.

Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial-temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo-conjugated-polymer is designed via Stille polymerization, resulting in PSP-Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR-II light.

Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy.

Metastatic dissemination in breast cancer is regulated by specialized intravasation sites called "tumor microenvironment of metastasis" (TMEM) doorways, composed of a tumor cell expressing the actin-regulatory protein Mena, a perivascular macrophage, and an endothelial cell, all in stable physical contact. High TMEM doorway number is associated with an increased risk of distant metastasis in human breast cancer and mouse models of breast carcinoma. Here, we developed a novel magnetic resonance imaging (MRI) methodology, called TMEM Activity-MRI, to detect TMEM-associated vascular openings that serve as the portal of entry for cancer cell intravasation and metastatic dissemination.

Evidence for preserved insulin responsiveness in the aging rat brain.

Insulin appears to exert salutary effects in the central nervous system (CNS). Thus, brain insulin resistance has been proposed to play a role in brain aging and dementia but is conceptually complex and unlikely to fit classic definitions established in peripheral tissues. Thus, we sought to characterize brain insulin responsiveness in young (4-5 months) and old (24 months) FBN male rats using a diverse set of assays to determine the extent to which insulin effects in the CNS are impaired with age.

Corrected cerebral blood flow and reduced cerebral inflammation in berk sickle mice with higher fetal hemoglobin.

Fetal hemoglobin (HbF) is known to lessen the severity of sickle cell disease (SCD), through reductions in peripheral vaso-occlusive disease and reduced risk for cerebrovascular events. However, the influence of HbF on oxygen delivery to high metabolism tissues like the brain, or its influence on cerebral perfusion, metabolism, inflammation or function have not been widely studied. We employed a Berkley mouse model (BERK) of SCD with gamma transgenes q3 expressing exclusively human α- and β-globins with varying levels of γ globin expression to investigate the effect of HbF expression on the brain using magnetic resonance imaging (MRI), MRI diffusion tensor imaging (DTI) and spectroscopy (MRS) and hematological parameters.

Defective myelination in an RNA polymerase III mutant leukodystrophic mouse.

RNA polymerase (Pol) III synthesizes abundant short noncoding RNAs that have essential functions in protein synthesis, secretion, and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown.

Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats.

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood.

Central IGF-1 protects against features of cognitive and sensorimotor decline with aging in male mice.

Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging. To test this hypothesis, we generated inducible, brain-specific (TRE-IGF-1 × Camk2a-tTA) IGF-1 (bIGF-1) overexpression mice and studied effects on healthspan.

High fat diet aggravates cardiomyopathy in murine chronic Chagas disease.

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy.

Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.

To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation.

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection.

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about ten million people in its endemic regions of Latin America. After the initial acute stage of infection, 60-80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system, and heart. The challenges of Chagas disease have become global due to immigration.

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived.

No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice.

Gene therapy for sickle cell disease is currently in active trials. Collecting hematopoietic progenitor cells safely and effectively is challenging, however, because granulocyte colony stimulating factor, the drug used most commonly for mobilization, can cause life-threatening vaso-occlusion in patients with sickle cell disease, and bone marrow harvest requires general anesthesia and multiple hip bone punctures. Plerixafor is an inhibitor of the CXCR4 chemokine receptor on hematopoietic progenitor cells, blocking its binding to SDF-1 (CXCL12) on bone marrow stroma.

In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.

Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR).