How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV-associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

Semaphorin 3F induces colorectal cancer cell chemosensitivity by promoting P27 nuclear export.

Colorectal adenocarcinoma (CRC) is the third most common malignancy worldwide. Metastatic CRC has a poor prognosis because of chemotherapy resistance. Our previous study demonstrated that semaphorin 3F (SEMA3F) signaling may contribute to reversing chemotherapy resistance in CRC cells by reducing E-cadherin and integrin αvß3 expression levels. Another study showed that upregulation of p27 significantly increase the expression of E-cadherin and integrin. This study aimed to evaluate the effect of SEMA3F on P27 and whether it can reverse resistance in CRC cells. We compared the chemosensitivity of human colorectal cancer cell lines with different SEMA3F expression levels to 5-Fu through cell experiment and animal experiment. Then the interaction between SEMA3F and p27 and its possible mechanism were explored by Western Blot, immunofluorescence and immunocoprecipitation. We also compared the disease-free survival of 118 CRC patients with high or low expression of SEMA3F.The results showed that overexpresstion of SEMA3F enhanced the chemotherapy sensitivity and apoptosis of CRC cells in vitro and in vivo. Among 118 postoperative CRC specimens, the disease-free survival of patients with positive SEMA3F expression was significantly longer than that with negative SEMA3F expression after adjuvant treatment. Upregulation of SEMA3F in multicellular spheroid culture (MSC) could increase p27 phosphorylation at serine 10 (Ser10), subsequently promote the cytosolic translocation of P27. Overall, our results reveal a novel molecular mechanism: SEMA3F mediates the degradation of p27 and regulates its subcellular localization to enhance chemosensitivity to 5-Fu in CRC cells, rather than inhibits p27 expression.

Treatments of Ph-like acute lymphoblastic leukemia: a real-world retrospective analysis from a single large center in China.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of ALL. We retrospectively studied 70 cases with Ph-like ALL and here present the largest study of CAR-T cell treatment and haplo-HSCT for this leukemia. Median age was 26 years and median leukocyte count was 31.44 × 109/L. The proportion of patients receiving chemotherapy, KIs, CAR-T cells, and allo-HSCT was 19%, 30%, 46%, and 61%, respectively. The overall response rate was 62%, 73%, and 100% after one month of KI treatment combined with chemotherapy, CAR-T cell therapy, and allo-HSCT, respectively. Five-year DFS and OS were 35% and 51%, respectively. The five-year cumulative incidence of relapse and non-relapse mortality was 63% and 11%, respectively. Allo-HSCT was associated with a better DFS (p = 0.010) and OS (p = 0.000) by univariate analysis. In conclusion, allo-HSCT after KIs together with chemotherapy or CAR-T cell therapy is a safe and feasible treatment modality for Ph-like ALL.

Comparison of 2 Different Rabbit Anti-Thymocyte Globulin (r-ATG) Preparations: Thymocyte r-ATG versus T Lymphoblast Cell Line r-ATG in Allogeneic Hematopoietic Stem Cell Transplantation for Acquired Severe Aplastic Anemia: Propensity Score-Matched Analysis.

We retrospectively analyzed the outcomes of 214 patients with severe aplastic anemia (SAA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with rabbit anti-thymocyte globulin (r-ATG) or ATG-Fresenius (ATG-F). Using propensity score matching, we performed a case-control study comparing 44 and 23 patients in the r-ATG and ATG-F groups, respectively. The median time was 11 versus 11 days (P = .368) for myeloid engraftment and 11 versus 13 days (P = .030) for platelet engraftment in the r-ATG and ATG-F groups, respectively. The r-ATG group showed a lower incidence of grade III to IV acute graft-versus-host disease (GVHD) than the ATG-F group (2.27% versus 17.39%, P = .026). Similar outcomes were observed between the r-ATG and ATG-F groups for infection rate (59.09% versus 56.52%, P = .840), grade II to IV acute GVHD (20.45% versus 21.74%, P = .948), overall incidence of chronic GVHD (26.83% versus 22.73%, P = .704), moderate to severe chronic GVHD (9.76% versus 13.64%, P = .648), and transplantation-related mortality (11.36% versus 4.35%, P = .614). There was no statistical difference in 5-year overall survival (86.40% versus 95.7%, P = .245); GVHD-free, failure-free survival (77.30% versus 78.30%, P = .986); or health-related quality of life (P > .05) between r-ATG and ATG-F.

Potato (Solanum tuberosum L.) tuber-root modeling method based on physical properties.

The development of tuber-root models based on the physical properties of the root system of a plant is a prominent but complicated task. In this paper, a method for the construction of a 3D model of a potato tuber-root system is proposed, based on determining the characterization parameters of the potato tuber-root model. Three early maturing potato varieties, widely planted in Northeast China, were selected as the research objects. Their topological and geometric structures were analyzed to determine the model parameters. By actually digging potatoes in the field, field data measurement and statistical analysis of the parameters were performed, and a model parameter database was established. Based on the measured data, the root trajectory points were obtained by simulating the growth of the root tips. Then MATLAB was used to develop a system that would complete the construction of the potato tuber-root 3D visualization model. Finally, the accuracy of the model was verified experimentally. Case studies for the three different types indicated an acceptable performance of the proposed model, with a relative root mean square error of 6.81% and 15.32%, for the minimum and maximum values, respectively. The research results can be used to explore the interaction between the soil-tuber-root aggregates and the digging components, and provide a reference for the construction of root models of other tuber crops.

ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF­κB signaling pathway.

Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Krüppel erythroid myeloid oncogenic factor, is critical for the tumorigenicity and progression of various cancer types. ZBTB7 has been reported to promote the cell proliferation of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5­FU) resistance has not yet been studied. In the current study, ZBTB7 expression and function in 5­FU resistance in CRC were investigated using with multidisciplinary approaches, including western blot analysis, Transwell assay, CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level of proteins associated with cell invasion and epithelial-mesenchymal transition. ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells. IC50 values and cell viability were significantly reduced in cells with short hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5­FU administration decreased viability to a greater extent in the ZBTB7-shRNA group compared with the control, which was dose- and time-dependent. Analysis of gene expression omnibus data demonstrated that ZBTB7 mediated 5­FU resistance, potentially through nuclear factor (NF)-κB signaling. NF­κB inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5­FU resistance in CRC cells through NF­κB signaling. Thus, targeting ZBTB7 and NF­κB signaling may be an effective strategy to reverse 5­FU resistance in CRC.

[The immune effects of rituximab on dendritic cells derived from patients with primary immune thrombocytopenia].

OBJECTIVE: To explore the changes of surface antigen and function of rituximab on dendritic cells derived from patients with Primary immune thrombocytopenia (ITP) to further understand the effective mechanism of immunotherapy. METHODS: The peripheral blood mononuclear cells (PBMCs) were isolated from remission patients with ITP before and after low-dose rituximab infusion, and the PMNCs were stimulated for 5 days by rhGM-CSF and rhlL-4 in 5% CO2 air at 37°C incubator. Then all of DCs were cultured with TNF-α for 48 hours. The morphology of DCs was monitored under inverted microscope daily, and the surface antigens of the DCs were analysed by flow cytometry, meanwhile the levels of IL-12p70 and TGF-ß1 in supernatants were detected by ELISA, mix lymphocyte reaction was performed by MTT assay. RESULTS: (1) Rituximab-treated-DCs showed no obvious tree-like protruding compared with untreated-DCs. The former cells were small and most of nucleus were centric. (2) The expressions of HLA-DR, CD80, CD83 and CD86 on rituximab-treated-DCs \[56.37 ± 3.95)%, (36.41 ± 2.82)%, (30.45 ± 4.61)% and (41.98 ± 4.17)%, respectively\] were significantly lower than those untreated-DCs \[(73.71 ± 7.61)%, (55.14 ± 7.30)%, (80.91 ± 7.09)% and (59.03 ± 3.43)%, respectively\](all P < 0.05), the concentration of IL-12p70 was significantly lower, \[(66.87 ± 4.29)% vs (50.17 ± 14.52)%\], while that of TGF-ß1 \[(9.70 ± 0.31)%\] higher than the untreated-DCs \[(2.70 ± 0.36)%\] (P < 0.05). (3) The abilities to activate T cells proliferation of rituximab-treated-DCs reduced compared with untreated-DCs. CONCLUSION: The surface antigen of ITP-DCs and the concentration of IL-12p70 reduced after the low-dose rituximab infusion. The abilities to activate T cells proliferation reduced while the concentration of TGF-ß1 increased. Rituximab may achieve its therapeutic effect on ITP by downregulating the immunoreactivity of DCs.