Dual-state emission, mechanofluorochromism, and lipid droplet imaging of asymmetric D-π-A-D'-type triads.

Dual-state emission (DSE) is an emerging phenomenon wherein organic luminescent molecules display bright emissions in both molecularly isolated and packed states, addressing the challenge associated with the traditional paradigm of dyes with mono-state emission. This study presents the design and synthesis of two unsymmetrical triads, TPCA and TPCT, featuring a D-π-A-D' electronic structure by integrating phenothiazines, triphenylamines, and cyanostilbene. Photophysical assessments reveal that both molecules serve as robust DSEgens, exhibiting strong emissions in both solution and solid phases. TPCA displays ΦTHF 53.2% and Φsolids 43.2%, while TPCT exhibits ΦTHF 49.6% and Φsolids 37.5%. However, due to differences in molecular conformation and packing, they diverge in solid-state emission wavelengths and mechanofluorochromic behavior. In the solid state, TPCA emits strong red fluorescence, contrasting with TPCT, which emits orange fluorescence. Furthermore, TPCA demonstrates significant mechanofluorochromism (MFC), shifting from yellow to yellow-red upon mechanical grinding, while TPCT exhibits negligible MFC owing to conformational distinctions. As robust and low-toxic bioimaging agents, both TPCA and TPCT prove highly effective for lipid-droplet imaging studies. This research contributes valuable insights to the evolving field of DSE materials, elucidating the promising applications and mechanisms governing their versatile emission behaviors.

Complement C4d as a biomarker for systemic lupus erythematosus and lupus nephritis.

Background: Increasing studies in the last decade have led to the widespread understanding that C4d, a split product of complement component 4 (C4), is a potential biomarker for systemic lupus erythematosus (SLE) and lupus nephritis (LN).Purpose: The aim of this review is to summarize the highlights of studies investigating the use of C4d as a biomarker for diagnosing and monitoring SLE and LN patients.Data collection: we searched PubMed/Medline and Wanfang databases using the terms "C4d and systemic lupus erythematosus", "C4d and lupus nephritis", and "Complement C4d".Results: The deposition of C4d on circulating blood cells has been shown in several clinical studies to be a potential diagnostic marker that can be used to monitor patients with SLE. In addition, C4d deposits on circulating blood cells may be a helpful diagnostic marker for LN, one of the most severe complications of SLE. Meanwhile, studies utilizing renal biopsy specimens have indicated that C4d deposition in the renal peritubular capillaries of LN patients may predict more severe LN or a worse patient prognosis. Generally, a high plasma C4d level and a high plasma C4d/C4 ratio may also be promising indicators that can be used to monitor patients with SLE and LN.Conclusions: C4d detection may be a novel strategy for further clinical prediction and therapy.

Preparation and Characterization of Chitosan Nanoparticles for Chemotherapy of Melanoma Through Enhancing Tumor Penetration.

The poor solubility and permeability of most chemotherapeutic drugs lead to unsatisfactory bioavailability combined with insufficient drug concentration. In this study, positively charged nanoparticles based on chitosan were developed and synthesized to enhance tumor penetration capability of 10-Hydroxycamptothecin (HCPT) in order to improve the chemotherapeutic effect of melanoma. The HCPT encapsulated nanoparticles were noted as NPs/HCPT. NPs/HCPT was characterized by dynamic light scattering and zeta potential measurements. In addition, cell uptake, in vitro cytotoxicity, apoptosis and in vivo antitumor activity of NPs/HCPT were further investigated. The average diameter of NPs/HCPT was approximately 114.6 ± 4.1 nm. The viability of murine melanoma cell lines (B16F10 and B16F1) was significantly decreased due to interaction with NPs/HCPT. Moreover, NPs/HCPT significantly inhibited the progression of tumors. These investigations implied that cationic NPs/HCPT could be potentially applied as a promising drug delivery nanosystem.

Docetaxel enhances CD3+ CD56+ cytokine-induced killer cells-mediated killing through inducing tumor cells phenotype modulation.

Pretreatment with chemotherapeutic agents could sensitize human lung adenocarcinoma cells to the lyses of cytokine-induced killer (CIK) cells, however, the mechanism still unclear. We hypothesized that chemotherapeutic agents could induced immunogenic modulation (IM) and calreticulin (CRT) expression and enhanced the cytokine-induced killer (CIK) cells-mediated killing. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined the molecular and immunogenic consequences of chemotherapeutic agent exposure in lung adenocarcinoma cell SPC-A1 cells. Our results showed that the human lung adenocarcinoma cells displayed an increased sensitization to lyses of CD3+ CD56+ CIK cells after treatment with nonlethal/sublethal doses of docetaxel in vitro. Docetaxel treatment of tumor cells did not induce ATP or high-mobility group box 1 (HMGB1) secretion, or cell death. However, calreticulin (CRT) exposure was observed. Enhanced killing by CIK cells was mediated largely by CRT membrane translocation, as determined by functional knockdown of CRT, or CRT blocking antibody. This study provides evidence that the pretreatment with chemotherapeutic agents can sensitize tumor cells to the lyses of CD3+ CD56+ CIK cells in vitro through inducing immunogenic modulation and upregulating in target cells.

Combination doxorubicin and interferon-α therapy stimulates immunogenicity of murine pancreatic cancer Panc02 cells via up-regulation of NKG2D ligands and MHC class I.

BACKGROUND: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-α (IFN-α) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. MATERIALS AND METHODS: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-α (IFN-α) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-α (IFN-α) on the ligands of NK and T cells was assessed by flow cytometry. RESULTS: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-α (IFN-α) may be a potential strategy for treating pancreatic adenocarcinoma.