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In classical Hodgkin lymphoma (cHL)—characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells—tumor-associated macrophages (TAMs) play a pivotal role in tumor formation. However, the significance of direct contact between HRS cells and TAMs has not been elucidated. HRS cells and TAMs are known to express PD-L1, which leads to PD-1+ CD4+ T cell exhaustion in cHL. Here, we found that PD-L1/L2 expression was elevated in monocytes co-cultured with HRS cells within 1 h, but not in monocytes cultured with supernatants of HRS cells. Immunofluorescence analysis of PD-L1/L2 revealed that their upregulation resulted in membrane transfer called “trogocytosis” from HRS cells to monocytes. PD-L1/L2 upregulation was not observed in monocytes co-cultured with PD-L1/L2-deficient HRS cells, validating the hypothesis that there is a direct transfer of PD-L1/L2 from HRS cells to monocytes. In the patients, both ligands (PD-L1/L2) were upregulated in TAMs in contact with HRS cells, but not in TAMs distant from HRS cells, suggesting that trogocytosis occurs in cHL patients. Taken together, trogocytosis may be one of the mechanisms that induces rapid upregulation of PD-L1/L2 in monocytes to evade antitumor immunity through the suppression of T cells as mediated by MHC antigen presentation.

A method for predicting HIV drug resistance by using genotypes would greatly assist in selecting appropriate combinations of antiviral drugs. Models reported previously have had two major problems: lack of information on the 3D protein structure and processing of incomplete sequencing data in the modeling procedure. We propose obtaining the 3D structural information of viral proteins by using homology modeling and molecular field mapping, instead of just their primary amino acid sequences. The molecular field potential parameters reflect the physicochemical characteristics associated with the 3D structure of the proteins. We also introduce the Bayesian conditional mutual information theory to estimate the probabilities of occurrence of all possible protein candidates from an incomplete sequencing sample. This approach allows for the effective use of uncertain information for the modeling process. We applied these data analysis techniques to the HIV-1 protease inhibitor dataset and developed drug resistance prediction models with reasonable performance.

The use of fluorescent proteins has revolutionized our understanding of biological processes. However, the requirement for external illumination precludes their universal application to the study of biological processes in all tissues. Although light can be created by chemiluminescence, light emission from existing chemiluminescent probes is too weak to use this imaging modality in situations when fluorescence cannot be used. Here we report the development of the brightest luminescent protein to date, Nano-lantern, which is a chimera of enhanced Renilla luciferase and Venus, a fluorescent protein with high bioluminescence resonance energy transfer efficiency. Nano-lantern allows real-time imaging of intracellular structures in living cells with spatial resolution equivalent to fluorescence and sensitive tumour detection in freely moving unshaved mice. We also create functional indicators based on Nano-lantern that can image Ca 2+ , cyclic adenosine monophosphate and adenosine 5′-triphosphate dynamics in environments where the use of fluorescent indicators is not feasible. These luminescent proteins allow visualization of biological phenomena at previously unseen single-cell, organ and whole-body level in animals and plants. Luminescent proteins are important tools for biomedical imaging but tend to emit fairly little light. Saito et al. . describe a brighter version of a bioluminescent protein that can visualize intracellular dynamics of various signalling molecules with high spatial and temporal resolution.

High-throughput screening (HTS) is an essential process in drug discovery, requiring platforms that ensure reagent economy, high efficiency, and resistance to cross-contamination. Click chemistry is well suited for HTS because of its biocompatibility, high selectivity, and quantitative fluorescent readout. We focus on droplet-array sandwiching technology (DAST), in which two droplet microarrays (DMAs) are vertically opposed to achieve solute transport and reagent mixing by controlled contact and separation. Herein, we integrate click chemistry with DAST and evaluate its feasibility as a HTS platform. In DAST, DMAs are formed on wettability-patterned (WP; hydrophilic/hydrophobic) substrates, preserving resistance to cross-contamination. First, we immobilized dibenzocyclooctyne (DBCO) on a WP substrate and verified the occurrence of DBCO–azide reaction using an azide-functional fluorescent dye. The fluorescence intensity increased with concentration and reached a plateau at higher concentrations, indicating saturation behavior in the DBCO–azide click reaction. Second, acoustic mixing with repeated droplet contact–separation was applied to generate concentration gradients on a single substrate while maintaining droplet independence. Third, we qualitatively reproduced the expected concentration dependence of manual handling by combining DAST-based gradient formation with click reaction fluorescence readout. These results reveal that DAST enables a reagent-efficient, cross-contamination-resistant, and low-instrument-dependent HTS foundation for click-chemistry-based assays.

A composite hydrogel scaffold comprising chitosan, silk fibroin, extract, and Mimosa complex was fabricated and thoroughly characterized. Upon freeze-drying, the scaffolds displayed a uniform cylindrical geometry with a highly porous, interconnected polymeric network. Quantitative image analysis revealed a mean pore diameter of 43.09 ± 2.27 µm alongside an overall porosity of 61.4 ± 6.2%. ATR-FTIR and XRD analyses confirmed successful inclusion of the complex formation and the incorporation of all constituents into the final formulation. The scaffold exhibited a compressive modulus of 46.63 ± 22.71 kPa (dry) and 5.40 ± 3.73 kPa (hydrated), with a swelling ratio of 756.62 ± 114.08%, supporting its suitability for physiological applications. TGF-β3 loading via adsorption yielded an entrapment efficiency of approximately 79.18%, reflecting effective physical immobilization throughout the polymer matrix. Cytocompatibility was subsequently assessed using an indirect contact model combined with an MTT assay, both of which confirmed that TGF-β3-loaded scaffolds exerted no cytotoxic effects on chondrocytes. After 28 days in culture, scanning electron microscopy revealed pronounced cell adhesion, preservation of rounded cell morphology, and ECM deposition along pore walls and throughout interconnected channels. Immunofluorescence analysis further demonstrated a time-dependent accumulation of aggrecan and collagen type II within the three-dimensional scaffold architecture. Collectively, these findings suggest that the developed composite hydrogel scaffold is well-suited for cartilage-related in vitro culture applications.

Artocarpin, a prenylated flavonoid isolated from Artocarpus altilis heartwood, has emerged as a promising multi-targeted bioactive compound for combating UV-induced skin aging. This review provides a comprehensive overview of the molecular mechanisms and photoprotective efficacy of artocarpin across in vitro, in vivo and clinical study, based on the peer-reviewed literature published between 2012 and 2025, retrieved from PubMed, Scopus, and Web of Science. Delivery strategies designed to overcome the inherent physicochemical limitations of artocarpin on skin penetration are also discussed. Artocarpin demonstrates antioxidant effects through both direct free radical scavenging and activation of the Nrf2-ARE pathway, providing sustained cellular defense. Its anti-inflammatory properties target multiple signaling cascades, including the NF-κB and MAPK pathways, effectively mitigating UV-induced inflammatory response. The compound maintains dermal matrix homeostasis by inhibiting matrix metalloproteinase-1 (MMP-1) expression while preserving collagen synthesis and fibroblast mechanical function. Additionally, artocarpin exhibits selective apoptosis modulation, being cytoprotective in normal keratinocytes while acting as pro-apoptotic in damaged or abnormal cells, thereby supporting tissue homeostasis. It also inhibits melanogenesis through anti-inflammatory mechanisms rather than direct tyrosinase inhibition. Furthermore, artocarpin has been shown to induce autophagic cell death in certain cell lines; however, its role in UV-induced skin damages remains to be clarified. Despite these promising biological activities, the poor water solubility (<0.1 mg/mL) and high lipophilicity (log P ≈ 5) of artocarpin significantly limit its skin penetration. Lipid-based delivery systems, including liposomes, transfersomes, ethosomes, and nanostructured lipid carriers (NLCs), are presented as effective strategies to enhance transepidermal delivery, with each system offering distinct mechanistic advantages. Further investigations should prioritize the safety of artocarpin within each delivery system, as well as the synergistic co-encapsulation with complementary natural antioxidants to simultaneously target multiple mechanisms involved in UV-induced skin damage, thereby broadening its application in the cosmeceutical industry.

The development of optical methods to control cellular functions is important for various biological applications. In particular, heat shock promoter-mediated gene expression systems by laser light are attractive targets for controlling cellular functions. However, previous approaches have considerable technical limitations related to their use of UV, short-wavelength visible (vis), and infrared (IR) laser light, which have poor penetration into biological tissue. Biological tissue is relatively transparent to light inside the diagnostic window at wavelengths of 650–1,100 nm. Here we present a unique optical biotechnological method using carbon nanohorn (CNH) that transforms energy from diagnostic window laser light to heat to control the expression of various genes. We report that with this method, laser irradiation within the diagnostic window resulted in effective heat generation and thus caused heat shock promoter-mediated gene expression. This study provides an important step forward in the development of light-manipulated gene expression technologies.

In this study, stable nano-sized bubbles (nanobubbles [NBs]) were produced using the mechanical agitation method in the presence of perfluorocarbon gases. NBs made with perfluoropropane had a smaller size (around 400 nm) compared to that of those made with perfluorobutane or nitrogen gas. The lipid concentration in NBs affected both their initial size and post-formulation stability. NBs formed with a final lipid concentration of 0.5 mg/ml tended to be more stable, having a uniform size distribution for 24 h at room temperature and 50 h at 4 °C. In vitro gene expression revealed that NBs/pDNA in combination with ultrasound (US) irradiation had significantly higher transfection efficacy in colon C26 cells. Moreover, for in vivo gene transfection in mice left limb muscles, there was notable local transfection activity by NBs/pDNA when combined with US irradiation. In addition, the aged NBs kept at room temperature or 4 °C were still functional at enhancing gene transfection in mice. We succeeded in preparing stable NBs for efficient in vivo gene transfection, using the mechanical agitation method.

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor‐associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor‐promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor‐κB (NF‐κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF‐κB decoy into TAMs by ultrasound (US)‐responsive, mannose‐modified liposome/NF‐κB decoy complexes (Man‐PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF‐κB decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man‐PEG bubble lipoplexes and US exposure transferred the NF‐κB decoy into TAMs effectively. When the NF‐κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)‐10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL‐12, tumor necrosis factor‐α, and IL‐6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF‐κB decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF‐κB decoy efficiently by Man‐PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. We demonstrated that the combinatorial use of mannose‐modified bubble lipoplexes with ultrasound exposure achieved the efficient delivery of NF‐κB decoy oligonucleotides into tumor‐associated macrophages (TAM) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. Using this method, NF‐κB decoy transfer into TAM inhibited the malignant ascites progression significantly that may be the phenotypic conversion of TAM from M2 toward M1.

Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells, which may possess antitumor activity. Previously, we found that when the cationic liposomes complexes formed with CpG DNA (CpG DNA lipoplex) were administered intranasally, they could prevent pulmonary metastasis in mice. However, the mechanisms underlying this process are unknown. In the present study, we show that natural killer (NK) cells play an important role in preventing pulmonary metastasis and peritoneal dissemination in a mouse model of metastatic disease. Further, in vitro, the NK cells obtained from mice treated with CpG DNA lipoplex showed higher cytotoxicity compared with untreated mice and in vivo, depletion of NK cells (achieved through injection of rabbit anti-asialo GM1 serum), abolished the inhibitory effect of CpG DNA lipoplex on pulmonary metastasis and peritoneal dissemination. In contrast, macrophage elimination did not disrupt the effects of the CpG DNA lipoplex. These results suggest that intranasal administration of CpG DNA lipoplex could prevent pulmonary metastasis and peritoneal dissemination by activating NK cells.