Cisplatin is commonly used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer, but its immune-related mechanism is still unclear. Exploration of the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and explored the important function of these immune effects in the bladder cancer microenvironment in a mice tumor model. We found cisplatin induced immune response in bladder cancer by RNA sequencing and validated that cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8+ T cells and dendritic cells in a transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Our findings indicated a cisplatin-related immune effect in bladder cancer, and cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.

We aimed to examine whether the use of aspirin is associated with change in cognitive performance over time, and whether this association is modified by the cognitive stages. This study included a total of 1866 subjects, including 509 subjects with normal cognition (NC), 985 subjects with mild cognitive impairment (MCI), and 372 patients with Alzheimer’s disease (AD). In each group, we further categorized our subjects into two groups based on their aspirin using conditions: Aspirin users and non-aspirin users. Mini-Mental State Examination (MMSE) was the cognitive outcome. Linear mixed models were conducted to examine the longitudinal relationship between the use of aspirin and cognitive performance in each diagnostic group. In the cross-sectional analysis, there were no significant differences in MMSE scores between non-aspirin users and aspirin users in subjects with NC, subjects with MCI or patients with AD. In the longitudinal analysis, we detected an association of the baseline use of aspirin with cognitive decline (MMSE) over time in patients with AD, but not in the NC group or MCI group. Specifically, in AD patients, the use of aspirin at baseline was associated with slower cognitive decline over time. Our data may support an association between the use of aspirin and slower cognitive decline, while this association may be dependent on the clinical stages.

Objective: The objective of this study was to examine whether plasma transferrin levels are associated with longitudinal changes in cognitive performance in older individuals with normal cognition (CN), mild cognitive impairment (MCI), and mild Alzheimer’s disease (AD). Methods: At baseline, there were a total of 358 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, including 58 older individuals with CN, 198 older individuals with MCI, and 102 patients with AD. Linear mixed models were utilized to examine the associations of plasma transferrin levels with changes in cognitive performance over time after adjustment of several potential covariates. The Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were used to examine the global cognition of participants. Results: First, no significant differences in the plasma transferrin levels were observed across three diagnostic groups. Second, in the cross-sectional analyses, the baseline plasma transferrin levels were negatively associated with the MMSE scores in the CN group, but not in the MCI or the AD group. Third, in the longitudinal analyses, we found that a higher plasma transferrin was associated with a steeper cognitive decline in the MCI and AD groups, but not in the CN group. Conclusion: Higher plasma transferrin levels were associated with a steeper cognitive decline in participants with MCI and AD.

Objective: Oncolytic virotherapy is a promising alternative to conventional treatment, yet limited viral replication and immune-negative feedback are the major hurdles to effective viro-immunotherapy. Methods: In this study, we found that use of an adjuvant of embelin, a small molecular inhibitor of XIAP, increased the replication of oncolytic vaccinia virus (OVV) by mitigating antiviral innate immunity. Moreover, embelin suppresses constitutive STAT3 phosphorylation and mitigates OVV-induced activation of STAT3 in lymphoma. In the subcutaneous lymphoma model, embelin significantly enhanced the therapeutic efficacy of OVV and prolonged the survival. In addition, embelin significantly increased the OVV-induced infiltration of T cells and NK cells and decreased the number of OVV-induced myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Results: Our results explored the ability of OVV and embelin in combination to enhance lymphoma cell lysis, revealing a beneficial combinatorial effect wherein both lymphoma cell lysis and OVV replication were enhanced both in vitro and in an in vivo murine model system. Conclusion: Our findings indicate the utility of embelin as an adjuvant for oncolytic viro-immunotherapy.