A novel ROS-Related chemiluminescent semiconducting polymer nanoplatform for acute pancreatitis early diagnosis and severity assessment

Abstract Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future

Systematic Analysis of a Xenograft Mice Model for KSHV⁺ Primary Effusion Lymphoma (PEL)

<div><p>Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the <i>in vivo</i> effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV⁺ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated <i>in vivo</i> exhibit unique biology, differing from one another or from their parental cell lines propagated through <i>in vitro</i> culture. Therefore, we used a KSHV⁺ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells <i>in vivo</i> display unique features to those passed <i>in vitro</i>, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.</p></div

Cytokines production from ascites cells in NOD/SCID mice.

<p>Ascites fractions were collected from NOD/SCID mice as described above, then both human and mouse cytokines within the supernatant were measured by flow cytometry and ELISA as described in Methods. Error bars represent the S.E.M. for two experiments. ** = p<0.01.</p

Establishment of a xenograft model for KSHV⁺ primary effusion lymphoma (PEL).

<p>(<b>A–C</b>) 10⁷ BCBL-1 cells or PBS controls were injected into the peritoneal cavity of NOD/SCID mice. Mice weight was recorded every week, 35 days later, mice were sacrificed and the volume of ascites fluid was measured. Error bars represent the S.E.M. for two experiments. ** =  p<0.01. (<b>D</b>) The ascites fractions were resuspended in PEL medium for 2 h in fibronectin-coated plates. Cells remaining in suspension were separated from adherent cells, and the expression of viral latent protein LANA, PEL-surface marker, CD45, CD138 and EMA was detected by immunofluorescence as described in Methods, respectively.</p

Solid tumors in a xenograft model for KSHV⁺ PEL.

<p>10⁷ BCBL-1 cells were intraperitoneally injected into NOD/SCID mice, 42 days later, mice were sacrificed and the solid tumors (indicated by the arrows) were found on the multiple sites in mice.</p