Angioimmunoblastic T cell lymphoma (AITL) is an aggressive form of non-Hodgkin lymphoma derived from mature T cells. However, the underlying pathogenesis of AITL remains unresolved. We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.

Some studies have investigated the prognostic value exhibited by the Prognostic Nutritional Index (PNI) in patients suffering diffuse large B-cell lymphoma (DLBCL), but varying results were obtained. In order to determine the specific prognostic value more accurately, a meta-analysis was conducted in this study.

Diffuse large B cell lymphoma (DLBCL) has previously been demonstrated to contribute to the mortality of lymphoma with various aggressive features. The prognostic role of the biomarkers latent membrane protein (LMP) 1 and microRNA-(miR)-155 in DLBCL remain controversial. The present study primarily aimed to assess the effect of LMP1 and miR-155 on the survival of DLBCL patients, and additionally evaluate the clinical features to observe their influence on outcomes, compared with previous studies. Formalin-fixed and paraffin-embedded samples were collected from our center between May 2010 and December 2011. Microarray analysis, immunohistochemical analysis and reverse transcription-quantitative polymerase chain reaction were used to evaluate the expression of LMP1 and miR-155. The association between biomarkers or clinical features and patient outcomes was assessed using the log-rank statistical test, Cox proportional hazard model and Kaplan-Meier method. SPSS software was used to statistically analyze the data. A total of 82 patients were included in the present study. The results demonstrated that high expression of LMP1 and miR-155 may be associated with a poor progression-free survival rate, while a high International Prognostic Index score and high expression of LMP1 may be associated with a poor overall survival rate. These results indicated that LMP1 and miR-155 may be novel and reliable biomarkers for the prognostic prediction of lymphoma, and will potentially be analyzed in the future to evaluate patient prognosis.

Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future.

Recently, brentuximab vedotin has become a promising therapeutic approach for CD30-positive hematological malignancies, but its role in other relapsed or refractory malignant lymphoma needs to be proven. Brentuximab vedotin was demonstrated effective, but no study has summarized the concrete effect of brentuximab vedotin in malignant lymphoma. To truly know the role of brentuximab vedotin, we performed a systematic review of the literature and a meta-analysis of all known prospective trials, to assess the value of brentuximab vedotin for patients with relapsed and refractory malignant lymphoma.

Anthracycline chemotherapy is commonly used in the treatment of diffuse large B-cell lymphoma (DLBCL). Treatment-related cardiotoxicity (TRC) is defined as when the patient is identified to have one of the following clinical manifestations: Symptomatic heart failure, cardiac death, arrhythmia, infarction, a decrease in left ventricular ejection fraction (LVEF) of >15% from baseline or a decrease in LVEF of >10 to <50%. TRC may induce severe cardiac failure or cardiac arrhythmia as the main cause of death. The present study aimed to investigate the prognostic value of the summed rest score (SRS) in gated myocardial perfusion imaging (G-MPI) for the early detection of TRC caused by anthracycline chemotherapy in patients with DLBCL. A total of 36 DLBCL patients were enrolled in the present study, and a series of parameters were compared at baseline and after chemotherapy. According to the occurrence of TRC during the observation period, the patients were divided into two groups, and parameters associated with cardiac function were compared. The SRS in G-MPI and the corrected QT interval in the electrocardiogram were significantly different before and after chemotherapy (P=0.012 and P=0.015, respectively). By comparing parameters associated with cardiac function between the TRC group (n=22) and the no-TRC group (n=14), it was found that only SRS was significantly different (P=0.012). Multivariate logistic regression analysis showed that the SRS level was the only independent predicator for TRC (P=0.018; HR, 6.053; 95% CI, 1.364-26.869). Receiver operating characteristic curve analysis identified an optimal SRS cutoff of >1 for predicting TRC after anthracycline chemotherapy (P<0.001). Overall, the G-MPI SRS level was an early indicator for TRC surveillance in patients with DLBCL after anthracycline chemotherapy. The application of G-MPI SRS in clinical practice may contribute to early treatment and a subsequent decrease in mortality caused by such cardiovascular complications.

The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKCβ-mediated FAK activation dependent manner.

The transcription factor RORγt regulates differentiation of the TH17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγtM) that 'preferentially' disrupted TH17 differentiation but not thymocyte development. Mice expressing RORγtM were resistant to EAE associated with defective TH17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγtM showed less ubiquitination at Lys69 that was selectively required for TH17 differentiation but not T cell development. This study will inform the development of treatments that selectively target TH17 cell-mediated autoimmunity but do not affect thymocyte development or induce lymphoma.

Myocardial ischemia/reperfusion (I/R) induces cardiac cell injury; however, the mechanism underlying cardiac damage remains unclear. A previous study demonstrated that triptolide (TP) exerts protective effects against I/R in cerebral cells. The present study aimed to evaluate the protective effects of TP on cardiac cells, and investigated the potential mechanisms involved in I/R‑induced damage. Rats and cardiac H9C2 cells undergoing I/R were pretreated with TP, and cell damage was assessed in vivo and in vitro. Hematoxylin and eosin and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling staining were employed to evaluate I/R injury in rat cardiac tissue. Inflammatory factors, including tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6, were detected by ELISA. Biochemical analyses were performed to evaluate the bioactivity of superoxide dismutase, malondialdehyde and catalase. In addition, viability of H9C2 cells was measured using the Cell Counting kit 8 assay. Flow cytometry was used to evaluate cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, the expression levels of proteins associated with apoptosis, peroxide and inflammation were measured using western blot analysis. H9C2 cells were also treated with N‑acetylcysteine and pyrrolidine dithiocarbamate, and cell injury was assessed after peroxidation or I/R. The results demonstrated that TP exerted a significant protective effect on cardiac cells in vivo and in vitro. TP reduced the inflammatory response, as determined by nuclear factor‑κB inhibition. In addition, TP decreased ROS‑mediated lipid peroxidation, and reduced ROS generation. TP also inhibited cell apoptosis by activating the extracellular signal‑regulated kinase 1/2 pathway. In conclusion, TP may protect cardiac cells from I/R injury; the potential protective mechanisms of TP against I/R include anti‑inflammatory action, antioxidation and apoptotic resistance.

The bone marrow (BM) is not only a reservoir of hematopoietic stem cells but a repository of immunological memory cells. Further characterizing BM-resident memory T cells would be helpful to reveal the complicated relationship between the BM and immunological memory. In this study, we identified CD122high stem cell antigen-1 (Sca-1) high B cell lymphoma 2 (Bcl-2) high CD4+ stem cell-like memory T cells (TSCMs) as a distinct memory T cell subset, which preferentially reside in the BM, where they respond vigorously to blood-borne antigens. Interestingly, the natural CD4+ TSCMs homing to the BM colocalized with VCAM-1+ IL-15+ IL-7+ CXCL-12+ stromal cells. Furthermore, compared to spleen-resident CD4+ TSCMs, BM-resident TSCMs induced the production of high-affinity antibodies against influenza by B lymphocytes more efficiently. Taken together, these observations indicate that the BM provides an appropriate microenvironment for the survival of CD4+ TSCMs, which broadens our knowledge regarding the memory maintenance of antigen-specific CD4+ T lymphocytes.

The E3 ligase CRL4DCAF2 is believed to be a pivotal regulator of the cell cycle and is required for mitotic and S phase progression. The NEDD8-targeting drug MLN4924, which inactivates cullin ring-finger ubiquitin ligases (CRLs), has been examined in clinical trials for various types of lymphoma and acute myeloid leukemia. However, the essential role of CRL4DCAF2 in primary myeloid cells remains poorly understood. MLN4924 treatment, which mimics DCAF2 depletion, also promotes the severity of mouse psoriasis models, consistent with the effects of reduced DCAF2 expression in various autoimmune diseases. Using transcriptomic and immunological approaches, we showed that CRL4DCAF2 in dendritic cells (DCs) regulates the proteolytic fate of NIK and negatively regulates IL-23 production. CRL4DCAF2 promoted the polyubiquitination and subsequent degradation of NIK independent of TRAF3 degradation. DCAF2 deficiency facilitated NIK accumulation and RelB nuclear translocation. DCAF2 DC-conditional knockout mice displayed increased sensitivity to autoimmune diseases. This study shows that CRL4DCAF2 is crucial for controlling NIK stability and highlights a unique mechanism that controls inflammatory diseases.

Clinical evidence suggests that poor persistence of chimeric antigen receptor-T cells (CAR-T) in patients limits therapeutic efficacy. Here, we designed a CAR with recyclable capability to promote in vivo persistence and to sustain antitumor activity. We showed that the engagement of tumor antigens induced rapid ubiquitination of CARs, causing CAR downmodulation followed by lysosomal degradation. Blocking CAR ubiquitination by mutating all lysines in the CAR cytoplasmic domain (CARKR) markedly repressed CAR downmodulation by inhibiting lysosomal degradation while enhancing recycling of internalized CARs back to the cell surface. Upon encountering tumor antigens, CARKR-T cells ameliorated the loss of surface CARs, which promoted their long-term killing capacity. Moreover, CARKR-T cells containing 4-1BB signaling domains displayed elevated endosomal 4-1BB signaling that enhanced oxidative phosphorylation and promoted memory T cell differentiation, leading to superior persistence in vivo. Collectively, our study provides a straightforward strategy to optimize CAR-T antitumor efficacy by redirecting CAR trafficking.

The complete degradation of the cellulose requires the synergistic action of endo-β-glucanase, exo-β-glucanase, and β-glucosidase. But endo-β-glucanase and exo-β-glucanase can be recovered by solid-liquid separation in cellulose hydrolysis by their cellulose binding domain (CBD), however, the β-glucosidases cannot be recovered because of most β-glucosidases without the CBD, so additional β-glucosidases are necessary for the next cellulose degradation. This will increase the cost of cellulose degradation.

β-Xylosidase is an important constituent of the hemicellulase system and it plays an important role in hydrolyzing xylooligosaccharides to xylose. Xylose, a useful monose, has been utilized in a wide range of applications such as food, light, chemical as well as energy industry. Therefore, the xylose-tolerant β-xylosidase with high specific activity for bioconversion of xylooligosaccharides has a great potential in the fields as above.