Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation

Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the "vector" of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.

Reliability and Validity of Chinese Version of the Perceived Competence Scale for Disaster Mental Health Workforce: A Cross-Sectional Study

Objective@#This study aimed to translate the English version of the Perceived Competence Scale for Disaster Mental Health Workforce (PCS-DMHW) into Chinese, and to test its reliability and validity in Chinese mental health workers. @*Methods@#With the consent of Professor Choi, Keimyung University, Korea, and the authorization of the scale, the English version of PCS-DMHW was translated, retranslated and culturally debugged to form the Chinese version of PCS-DMHW. The general information questionnaire and the Chinese version of PCS-DMHW scale were used to investigate 706 mental health workforce from 9 tertiary hospitals in Sichuan province in China from March 24, 2020 to April 14, 2020. The Cronbach’s α coefficient was used to evaluate the internal consistency reliability of the scale, and the test-retest correlation coefficient r was used to evaluate the test-retest reliability of the scale. The content validity indexes (CVI) and exploratory factor analysis (EFA) was used separately for evaluating the content validity and structure validity of the scale. @*Results@#The Cronbach’s α coefficient of the Chinese version of PCS-DMHW total scale, individual competences and organizational competences subscale was 0.978, 0.956, and 0.964, respectively. The test-retest reliability of the total scale, individual competences and organizational competences subscale was 0.949, 0.932 and 0.927, respectively. The item-level CVI of all scale were ranged from 0.833–1.000, the scale-level CVI (S-CVI)/universal agreement of the total scale, individual competences and organizational competences subscale was 0.833, 0.875, and 0.857, respectively, and the S-CVI/average was 0.972, 0.979, and 0.976, respectively. EFA showed that two principal components were extracted from the subscale of individual competences and organizational competences. @*Conclusion@#The Chinese version of PCS-DMHW has good reliability and validity, and can be widely used in China.

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.