-
Research (Washington, D.C.) 2023Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with... (Review)
Review
Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.
PubMed: 37705962
DOI: 10.34133/research.0211 -
Nature Neuroscience Dec 2023The amygdala is a brain region primarily associated with emotional response. The use of genetic markers and single-cell transcriptomics can provide insights into...
The amygdala is a brain region primarily associated with emotional response. The use of genetic markers and single-cell transcriptomics can provide insights into behavior-associated cell state changes. Here we present a detailed cell-type taxonomy of the adult mouse amygdala during fear learning and memory consolidation. We perform single-cell RNA sequencing on naïve and fear-conditioned mice, identify 130 neuronal cell types and validate their spatial distributions. A subset of all neuronal types is transcriptionally responsive to fear learning and memory retrieval. The activated engram cells upregulate activity-response genes and coordinate the expression of genes associated with neurite outgrowth, synaptic signaling, plasticity and development. We identify known and previously undescribed candidate genes responsive to fear learning. Our molecular atlas may be used to generate hypotheses to unveil the neuron types and neural circuits regulating the emotional component of learning and memory.
Topics: Mice; Animals; Neuronal Plasticity; Amygdala; Fear; Neurons; Memory
PubMed: 37884748
DOI: 10.1038/s41593-023-01469-3 -
Chemical Reviews May 2024Since the last century, we have witnessed the development of molecular magnetism which deals with magnetic materials based on molecular species, i.e., organic radicals... (Review)
Review
Since the last century, we have witnessed the development of molecular magnetism which deals with magnetic materials based on molecular species, i.e., organic radicals and metal complexes. Among them, the broadest attention was devoted to molecule-based ferro-/ferrimagnets, spin transition materials, including those exploring electron transfer, molecular nanomagnets, such as single-molecule magnets (SMMs), molecular qubits, and stimuli-responsive magnetic materials. Their physical properties open the application horizons in sensors, data storage, spintronics, and quantum computation. It was found that various optical phenomena, such as thermochromism, photoswitching of magnetic and optical characteristics, luminescence, nonlinear optical and chiroptical effects, as well as optical responsivity to external stimuli, can be implemented into molecule-based magnetic materials. Moreover, the fruitful interactions of these optical effects with magnetism in molecule-based materials can provide new physical cross-effects and multifunctionality, enriching the applications in optical, electronic, and magnetic devices. This Review aims to show the scope of optical phenomena generated in molecule-based magnetic materials, including the recent advances in such areas as high-temperature photomagnetism, optical thermometry utilizing SMMs, optical addressability of molecular qubits, magneto-chiral dichroism, and opto-magneto-electric multifunctionality. These findings are discussed in the context of the types of optical phenomena accessible for various classes of molecule-based magnetic materials.
PubMed: 38687182
DOI: 10.1021/acs.chemrev.3c00840 -
Cell Death & Disease Jul 2023Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2... (Review)
Review
Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2 diabetes (T2D) associated with developing cardiovascular events and death. Here, we summarize experimental and human evidence of vascular NO• resistance in T2D and discuss its underlying mechanisms. Human studies indicate a ~ 13-94% decrease in the endothelium (ET)-dependent vascular smooth muscle (VSM) relaxation and a 6-42% reduced response to NO• donors, i.e., sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), in patients with T2D. A decreased vascular NO• production, NO• inactivation, and impaired responsiveness of VSM to NO• [occurred due to quenching NO• activity, desensitization of its receptor soluble guanylate cyclase (sGC), and/or impairment of its downstream pathway, cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)] are the known mechanisms underlying the vascular NO• resistance in T2D. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) and vascular insulin resistance are key players in this state. Therefore, upregulating vascular NO• availability, re-sensitizing or bypassing the non-responsive pathways to NO•, and targeting key vascular sources of ROS production may be clinically relevant pharmacological approaches to circumvent T2D-induced vascular NO• resistance.
Topics: Humans; Nitric Oxide; Diabetes Mellitus, Type 2; Reactive Oxygen Species; Nitric Oxide Donors; Cyclic GMP
PubMed: 37433795
DOI: 10.1038/s41419-023-05935-5 -
Nature Communications Jul 2023Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which...
Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.
Topics: Humans; Genes, Immunoglobulin Heavy Chain; Genes, Immunoglobulin; Alleles; Germ-Line Mutation; Immunoglobulin Heavy Chains
PubMed: 37479682
DOI: 10.1038/s41467-023-40070-x -
Plant Science : An International... Dec 2023NAC family gene - SNAC1 (Stress-responsive NAC1) is responsive to drought, salt, cold stress, and ABA. It acts as a regulator in mediating tolerance to abiotic stress... (Review)
Review
NAC family gene - SNAC1 (Stress-responsive NAC1) is responsive to drought, salt, cold stress, and ABA. It acts as a regulator in mediating tolerance to abiotic stress through different pathways. Abiotic stress, among them drought and salinity, are adverse factors for plant growth and crop productivity. SNAC1 was an object of high interest according to the effect of improved drought and salt tolerance when overexpressed in different plant species such as rice, wheat, barley, cotton, maize, banana, or oat. SNAC1 functions by regulating the expression of genes that contain the NAC Recognized Sequence (NACRS) within their promoter region. This gene is induced by drought, specifically in guard cells. Its downstream targets have been identified. The role of SNAC1 in molecular and physiological responses during abiotic stress has been proposed, but this knowledge still needs to be expanded. Here, we describe recent advances in understanding the action of SNAC1 in adapting plants to abiotic stress.
Topics: Plant Proteins; Stress, Physiological; Gene Expression Regulation, Plant; Droughts; Salt Tolerance; Transcription Factors
PubMed: 37813193
DOI: 10.1016/j.plantsci.2023.111894 -
Cancer Letters Nov 2023PARP inhibitors (PARPi) are transforming the current treatment landscape of metastatic castration-resistant prostate cancer. By reanalysing published data on olaparib,... (Review)
Review
PARP inhibitors (PARPi) are transforming the current treatment landscape of metastatic castration-resistant prostate cancer. By reanalysing published data on olaparib, talazoparib, rucaparib and niraparib, we provide a concise overview of responses by molecular subgroup. As monotherapy, all PARPi showed comparable efficacy and the same hierarchy in responsiveness: patients with tumours harbouring aberrations in BRCA1 or BRCA2 (BRCAm) evidently demonstrate superior responses when compared to aberrations in other homologous recombination repair (HRR) related genes. Niraparib seems to cause more grade ≥3 adverse events in comparison to other PARPi. PARPi have also been combined with androgen-receptor signalling inhibitors (ARSI) for both patients with tumours harbouring aberrations in HRR genes (HRRm), and molecularly unselected patients. Compared to wildtype, BRCAm patients responded best, followed by HRRm. Olaparib-abiraterone, niraparib-abiraterone, and talazoparib-enzalutamide all prolonged progression-free survival compared to an ARSI alone in HRRm patients. In the non-HRRm subgroup, only olaparib-abiraterone and talazoparib-enzalutamide were effective. Results for the combination of rucaparib with enzalutamide are yet to be reported. The rate of grade ≥3 adverse events for the combination regimens is 10-30% higher when compared to an ARSI alone. Given the limited efficacy in unselected patients, these PARPi-ARSI combinations may be best reserved for selected patients.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Phenylthiohydantoin; Benzamides
PubMed: 37689306
DOI: 10.1016/j.canlet.2023.216367 -
Molecules and Cells Jul 2023cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily... (Review)
Review
cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to -acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.
Topics: Animals; Cyclic AMP Response Element-Binding Protein; Phosphorylation; Cell Differentiation; Promoter Regions, Genetic; Transcription, Genetic
PubMed: 37013623
DOI: 10.14348/molcells.2023.2193 -
Chemical Science May 2024Molecular photoswitches are potent tools to construct dynamic functional systems and responsive materials that can be controlled in a non-invasive manner. As P-type...
Molecular photoswitches are potent tools to construct dynamic functional systems and responsive materials that can be controlled in a non-invasive manner. As P-type photoswitches, stiff-stilbenes attract increasing interest, owing to their superiority in quantum yield, significant geometric differences between isomers, excellent thermostability and robust switching behavior. Nevertheless, the UV-light-triggered photoisomerization of stiff-stilbenes has been a main drawback for decades as UV light is potentially harmful and has low penetration depth. Here, we provided a series of -formylated stiff-stilbenes by Rieche -formylation to achieve all-visible-light-responsiveness. Additional phenolic groups provide access to late-stage chemical modification facilitating design of molecules responsive to visible light. Remarkably, the photoisomerization of aldehyde-appended stiff-stilbenes could be fully manipulated using visible light, accompanied by a high photostationary state (PSS) distribution. These features render them excellent candidates for future visible-light-controllable smart materials and dynamic systems.
PubMed: 38725493
DOI: 10.1039/d4sc00983e -
Chemical Science Nov 2023Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the... (Review)
Review
Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the resolution of US imaging, and facilitate therapeutic US procedures by promoting local drug delivery or allowing temporary biological barrier opening at moderate acoustic powers. Polymeric materials offer a high degree of control over physicochemical features concerning responsiveness to US, tuning chain composition, length and rigidity. This level of control cannot be achieved by materials made of lipids or proteins. In this perspective, we present key engineered polymeric materials that respond to US, including microbubbles, gas-stabilizing nanocups, microcapsules and gas-releasing nanoparticles, and discuss their formulation aspects as well as their principles of US responsiveness. Focusing on microbubbles as the most common US-responsive polymeric materials, we further evaluate the available chemical toolbox to engineer polymer shell properties and enhance their performance in US imaging and US-mediated drug delivery. Additionally, we summarize emerging applications of polymeric microbubbles in molecular imaging, sonopermeation, and gas and drug delivery, based on refinement of MB shell properties. Altogether, this manuscript provides new perspectives on US-responsive polymeric designs, envisaging their current and future applications in US imaging and therapy.
PubMed: 37969594
DOI: 10.1039/d3sc04339h