Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study.

Background: In clinical hematology, diffuse large B-cell lymphoma (DLBCL) is notably heterogeneous and varies in prognosis. Serum albumin (SA) is considered a biomarker of prognostic value in a number of hematologic malignancies. However, current knowledge of the association between SA levels and survival is limited, especially in DLBCL patients aged ≥70 years. Thus, this study sought to assess the prognostic value of SA levels among this age group of patients. Methods: The data of DLBCL patients aged ≥70 years at the Shaanxi Provincial People's Hospital in China from 2010 to 2021 were retrospectively reviewed. The SA levels were measured using standard procedures. The Kaplan-Meier method was used to estimate survival time, and the Cox proportional hazards model for time-to-event data was used to identify potential risk factors. Results: The data of 96 participants were included in the study. The univariate analysis showed that B symptoms, Ann Arbor stage III or IV of the disease, high International Prognostic Index (IPI) scores, high NCCN-IPI scores, and low SA levels were prognostic factors for an undesirable overall survival (OS) rate. The multivariate analysis showed that a high SA level (hazard ratio: 0.43; 95% confidence interval: 0.2-0.88; P=0.022) was an independent prognostic factor of superior outcomes. Conclusions: An SA level ≥4.0 g/dL was identified as an independent biomarker of prognostic value for DLBCL patients aged ≥70 years.

A novel deformable liposomal hydrogel loaded with a SREBP-1-inhibiting polypeptide for reducing sebum synthesis in golden hamster model.

Excessive sebum is the major factor involved in the pathophysiology of seborrheic diseases. Chemical medicines can result in mild to severe side effects. Polypeptides with much less side effects make them ideal for reducing sebum synthesis. Sterol regulatory element-binding proteins-1 (SREBP-1) is necessary for the biosynthesis of sterols. A SREBP-1-inhibiting polypeptide (SREi), which competitively inhibits the ubiquitination of Insig-1 so as to suppress the activation of SREBP-1 was selected as an active ingredient and formulated into skin topical preparations. The SREi anionic deformable liposomes contained sodium deoxycholate (SDCh) at the concentration of 4.4 mg/mL (SREi-ADL3) and SREi-ADL3 in 0.3% (w/v) carbomer hydrogel (SREi-ADL3-GEL) were prepared and characterized. The SREi-ADL3 presented a high entrapment efficiency of 92.62 ± 6.32%, a particle size of 99.54 ± 7.56 nm and a surface charge of -19.18 ± 0.45 mV. SREi-ADL3-GEL exhibited a sustained release behavior, a higher stability, a much more cellular uptake ability and transdermal absorption. In vivo golden hamster model confirmed that SREi-ADL3-GEL presented the strongest inhibitory effect on sebaceous gland growth and sebum synthesis by down-regulating the mRNA and protein expression of SREBP-1, fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase 1 (ACC1). As confirmed by histological analysis, only a small amount of sebaceous gland lobes with the lightest staining intensity and the smallest dyeing area could be observed in the SREi-ADL3-GEL group. Taken together, SREi-ADL3-GEL displayed potential applications in sebum excessive production related diseases.

Evaluation of poly(N-isopropylacrylamide)/tetraphenylethylene/amphotericin B-based visualized antimicrobial nanofiber wound dressing for whole skin wound healing in rats.

The aim of this work is to develop a novel nanofiber wound dressing with multiple functional properties that combines suitable mechanical properties, slow and controlled drug release, antifungal activity, and visual drug monitoring to accelerate wound healing while reducing systemic circulation of the drug, achieving reduced dose and side effects, and achieving patient satisfaction and compliance. In this paper, visualized nanofiber films were prepared using electrostatic spinning technology. This nanofiber wound dressing has soft tissue-like mechanical and antifungal properties and is biocompatible. In particular, the poly(N-isopropylacrylamide) (PNIPAAm)/tetraphenylethylene (TPE)/amphotericin B (AMB) nanofiber films showed good performance in terms of antifungal activity and cytocompatibility compared with medical gauze, and significantly accelerated the wound healing process in a mouse total wound defect model with PCL+PVP+TPE+AMB+PNIPAAm. The wound healing rate of nanofibrous membrane group was 100% at 14 days. In addition, histological analysis, collagen deposition and immunohistochemistry showed, for example, fewer inflammatory cells, more fibroblasts around the damaged area, increased wound epithelial atrophy, reduced granulation tissue, connective tissue reconstruction, epithelial tissue formation, and abundant small angiogenesis in the dermis near the epidermis; a higher level of collagen deposition fraction of 49.97%; and a simultaneous reduction in HIF-1α production and upregulated the expression of CD31. In conclusion, this antifungal nanofiber film showed promising applications throughout the skin wound healing process.

Sensitive and selective detection of carbamazepine in serum samples by bionic double-antibody sandwich method based on cucurbit[7]uril and molecular imprinted polymers.

A novel bionic enzyme-linked immunosorbent assay (BELISA) based on double-antibody sandwich method is firstly designed for the detection of carbamazepine (CBZ) in human serum samples. In this BELISA system, cucurbit[7]uril (CB[7]) is employed as an artificial capture antibody (cAb), and molecularly imprinted polymers (MIPs) is used as an artificial detection antibody (dAb). Nanozymes (PdNPs) as signal generators are integrated with MIPs. This couple of bionic antibodies exhibits not only the excellent physical and chemical stability, but also the superior molecular recognition ability. Based on two bionic antibodies that can selectively recognize different sites of CBZ molecule, a new BELISA method has been constructed for the first time. The proposed BELISA method displays a good linear relationship ranging from 2 to 20 µg mL-1. The detection limit is 0.37 µg mL-1, which can well meet clinical testing demand. It provides a more stable and economical method for clinical therapeutic drug monitoring (TDM).

Effects of Morphologies of Thermosensitive Electrospun Nanofibers on Controllable Drug Release.

Electrospun nanofibers is a promising and versatile avenue for building controlled drug release system because of the facile fabrication and the broad range of polymer materials. This research systematically studied the morphological effect of thermosensitive electrospun nanofibers, including porous and coaxial structures, on controllable drug release. Three types of drugs, nicotinamide, paracetamol, and ibuprofen, with different hydrophilicity were applied in this study. The data of drug release were all fitted to the first-order kinetic model regardless of the drug properties, and the release rates paralleled with their hydrophilicity. Sol-gel phase transition of the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel led to slower drug release at 37°C compared with those at 25°C. Regarding morphology, coaxial nanofibers could provide higher loading efficiency and slower drug release rather than porous nanofibers. Our research highlighted the overall effects of compound property, temperature, and the morphological structures of thermosensitive electrospun nanofibers on the controlled drug release. Our results concluded that hydrophobic drug encapsulated in the core-shell PNIPAAm nanofibers could perform excellent sustained release and also controllable release under temperature stumuli. Impact statement The behaviors for the controlled release of drugs loaded in the thermosensitive electrospun nanofibers could be affected by various factors including the properties of loaded drug, morphologies of nanofibrous, and lower critical solution temperatures of thermosensitive hydrogels. However, few systematical investigations have been performed in this area. In this article, we designed and fabricated porous and coaxial thermosensitive poly(N-isopropylacrylamide) electrospun nanofibers with different drug loading to study the comprehensive effect. This study suggested when adopting thermosensitive electrospun hydrogel nanofibers as the controllable drug release carrier, the hydrophilicity of loaded compounds and the morphologies of nanofibers are necessary to be optimized.

Influence of dendritic cells on biological activity of the homologous CIK cells and its anti-leukemia effect in vitro.

This study was aimed to investigate the effect of cord blood dendritic cells (DCs) on the in vitro proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia cells of the homologous cytokine-induced killer (CIK) cells. DCs and CIK cells were induced from cord blood mononuclear cells. They were co-cultured at the ratio of 1:5, and CIK cells from cord blood or DC-CIK cells from peripheral blood were cultured as controls. Immunophenotypic changes were analyzed by flow cytometry, increased number of cells were counted by trypan-blue staining, the killing activity to leukemia cells was assayed by MTT, the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) in the cultured supernatant were detected by ELISA. The results showed that the proliferation capability of cord blood DC-CIK cells was significantly higher than that of cord blood CIK cells and peripheral blood DC-CIK cells (p < 0.05 and p < 0.05). Under the same condition, the rate of double positive cells with CD3(+)CD8(+) and CD3(+)CD56(+) in CIK cells was significantly enhanced by co-culture with cord blood DCs (p < 0.05). The level of IL-12, IFN-γ, and TNF-α in cultured supernatants of cord blood DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05, p < 0.05). Within the effector-target ratio range between 2.5:1 to 20:1, the activity of cord blood DC-CIK cells against all subtypes of acute leukemia cells was much higher than that of CIK cells (p < 0.05), and there was no significant difference among all subtypes of acute leukemia cells, which was the same with the killing effect of peripheral blood DC-CIK cells against leukemia cells. It is concluded that the proliferation capability and anti-leukemia effect of the homologous CIK cells can be enhanced by cord blood DCs. The proliferation capability of cord blood DC-CIK cells is stronger than that of peripheral blood DC-CIK cells, but there is no significant differences of cytotoxicity between DCs and CIK cells. As the cord blood is easily gained and does not easily cause a serious graft rejection, the DC-CIK cells should be clinically applied more extensively as novel immune therapy.

Biological activity of DC-CIK cells and its effect against leukemia cells in vitro.

This study was aimed to investigate the effect of dendritic cells (DC) on the proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia of cytokine-induced killer (CIK) cells in vitro. DCs and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by trypan-blue staining; the killing activity was detected by MTT assay; immunophenotype changes were analyzed by flow cytometry; the IL-12 and INF-gamma levels of the cultured supernatants were detected by ELISA kits. The results showed that the proliferation capability of DC-CIK cells was significantly higher than that of CIK cells (p < 0.05). Under the same condition, the ratio of double positive cells such as CD3(+) CD8(+), CD3(+) CD56(+) in CIK cells was significantly enhanced by co-cultured with DC cells (p < 0.05). The levels of IL-12 and INF-gamma in cultured supernatants of DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05). Within the effector-target ratio range between 5:1 to 40:1, the activity of DC-CIK cells against leukemia cells were much higher than that of CIK cells (p < 0.05), and this effect showed a positive correlation with the effector-target ratio. It is concluded that the proliferation capability of DC-CIK cells, the level of their secreted cytokines and their activity against leukemia cells are significantly higher than those of CIK cells. This research may suggest an approach for clinical immunotherapy against leukemia with DC-CIK cells.

[Influence of IFN-alpha on function of CML-DC in vitro and expression of chemokine with its receptor].

To study the influence of IFN-alpha on function of CML-DC cultured in vitro and expression of chemokine and its chemokine receptor, bone marrow mononuclear cells from 13 CML patients were cultured in the fetal calf serum culture system supplemented with rhSCF, rhFlt-3L for expansion system, and adding rhGM-CSF, rhTNF-alpha, rhIL-4, with or without rhIFN-alpha to induce DCs. After incubation for two weeks, the phenotypes of CML-DC were analyzed by direct immunofluorescence and flow cytometry. The concentration of MIP-3beta expressed by CML-DC in the supernatant were analyzed by ELISA. The proliferative ability of T cells from healthy volunteers stimulated by CML-DCs were measured by MTT assay. The results showed that expression of CD86, CD83, CD40, MHC-I class molecules, CCR7, the concentration of MIP-3beta expressed by CML-DC, and the proliferative ability of T cells stimulated by CML-DCs in IFN-alpha group were all significantly higher than that in control group (P < 0.01). It is concluded that the immunophenotype of CML-DCs can be partially changed by IFN-alpha to accelerate the maturation of CML-DCs, enhance the capacity of CML-DCs, and stimulate allogeneic T lymphocyte proliferation.

[Influence of interferon type I on dendritic cells in vitro - review].

Dendritic cells(DC) are specialized antigen-presenting cells that prime naive T cells to induce initial immune responses. The immature DC capture and process antigens in the periphery, then emigrate to lymphoid organs. There they complete their maturation by upregulating HLA-I, II molecules, costimulatory molecules (eg. CD80, CD86) and adhesive molecules (eg. CD50, CD54, CD58). More studies showed that in vitro only interferons type I (IFN-alpha, beta) accelerate DC maturation in a dose-dependent manner. The DC induced by IFN type I highly express HLA-A, B, C, HLA-DR, costimulatory molecules and adhesive molecules, and they express enhancing effect of T-cells stimulatory activity in vitro. Progress of research in this field was summarized in this paper.