Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

Bio-based epoxy vitrimer with inherent excellent flame retardance and recyclability via molecular design.

The development of biobased fire-safe thermosets with recyclability heralds the switch for a transition towards a circular economy. In this framework, we introduced a novel high-performance bio-epoxy vitrimer (named GVD), which was fabricated by forming a crosslinking network between bio-epoxy glycerol triglycidyl ether (Gte), varying amounts of reactive flame-retardant agent 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) (0-7 wt%) and a vanillin-based hardener (VA) with imine bonds. For instance, the epoxy vitrimer GVD5, featuring a DOPO content of 5 wt%, achieved a V-0 rating in the vertical burning test (UL-94) and obtained a limiting oxygen index (LOI) value of 31 %, surpassing the performance of pristine epoxy. Furthermore, the peak heat release rate and total heat release of GVD5 were reduced by 38.2 % and 26.3 %, respectively, compared to pristine epoxy. The GVD vitrimers further demonstrated exceptional reprocessability and recyclability, attributed to the presence of dynamic imine bonds within the topological crosslinking network. Remarkably, the epoxy vitrimers maintained the mechanical properties of the parent epoxy. Therefore, this work provides a facile strategy for fabricating high-performance and multi-functional bio-epoxy thermosets.

Relationship between chronic disease resource utilization and quality of life in coronary heart disease patients: A latent profile analysis.

AIMS: This study aimed to identify different profiles of chronic disease resource utilization among patients with coronary heart disease in Tibet and explore the relationship between these profiles and quality of life. DESIGN: A cross-sectional study. METHODS: Patients with coronary heart disease who were treated in a tertiary hospital in Tibet and its cooperative points from January 2021 to July 2021 were selected as the study participants. All participants completed a general information questionnaire, the Chronic Disease Resource Utilization Questionnaire (CIRS) and the Health Status Survey Short Form (SF-36). Chronic disease resource utilization was profiled, and its relationship to quality of life was explored using hierarchical linear regression. RESULTS: A total of 382 patients were enrolled in this study. Regarding chronic disease resource utilization, the participants were divided into three latent profiles: 'Poor utilization group' (n = 151), 'Effective utilization group' (n = 155) and 'Full utilization group' (n = 76). Different profiles of chronic disease resource utilization of patients were significantly associated with quality of life (R2 = .126, p < .001). CONCLUSION: Healthcare providers should identify patients with different profiles, define their utilization features of chronic disease resources and adopt targeted interventions to guide them in acquiring enough disease support resources to improve their quality of life. IMPLICATION: Understanding different resources using preferences of coronary heart disease patients can help healthcare providers and related sectors to provide other supports based on different profiles of patients, thus enhancing their quality of life. REPORTING METHOD: The study followed the STROBE guideline. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public involvement in the design of the study.

Eudesmane-type sesquiterpenoids from the aerial parts of Artemisia lavandulaefolia and their anti-pancreatic cancer activities.

Five undescribed eudesmane sesquiterpenoids, artemilavanins A-E, and one undescribed rearranged eudesmane sesquiterpenoid, artemilavanin F, were isolated from the 95% ethanol extract of the aerial parts of Artemisia lavandulaefolia DC., along with ten known compounds. The structures and configurations of undescribed compounds were mainly elucidated by spectroscopic analyses and single-crystal X-ray diffraction analysis. Among all isolated compounds, artemilavanin F exhibited inhibitory activity on PANC-1 pancreatic cancer cells with IC50 of 9.69 ± 2.39 µM. Artemilavanin F inhibited PANC-1 cell proliferation by induction of G2/M cell cycle arrest and apoptosis mediated by downregulation of cyclin-dependent kinases and accumulation of reactive oxygen species. Moreover, artemilavanin F inhibited the colony formation, cell migration and sphere formation of PANC-1 cells, indicating the suppression of stem-cell-like phenotype of PANC-1 cells. Further results confirmed that the expression of cancer stem cell markers such as Bmi1, CD44, CD133 were inhibited by artemilavanin F. Downregulation of epithelial-mesenchymal transition (EMT) markers such as N-cadherin and Oct-4 indicated the potential of artemilavanin F in prevention of metastasis.

[Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition].

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Self-efficacy and self-management mediate the association of health literacy and quality of life among patients with TB in Tibet, China: a cross-sectional study.

BACKGROUND: This study aimed to analyze the relationship between health literacy and quality of life in patients with TB in Tibet and explore the mediating effects of self-efficacy and self-management in the relationship between health literacy and quality of life. METHODS: We used a convenience sampling method to select 271 cases of patients with TB in Tibet to conduct a survey of their general information, health literacy, self-management, self-efficacy and quality of life, and to construct structural equation models. RESULTS: The total health literacy score of patients with TB in Tibet was 84.28±18.57, while the lowest score was for information acquisition ability (55.99±25.66). Scores for quality of life were generally lower than the norm (patients with chronic diseases from other cities in China) (p<0.01). Moreover, self-efficacy and self-management mediated the relationship between health literacy and quality of life (p<0.05). CONCLUSIONS: In Tibet, patients with TB have a low level of health literacy and an average level of quality of life. Emphasis should be placed on improving information access literacy, role-physicals and role-emotional to improve overall quality of life. The mediating roles of self-efficacy and self-management between health literacy and quality of life may provide a basis for further interventions.

Health literacy and quality of life of patients with coronary heart disease in Tibet, China: The mediating role of self-efficacy and self-management.

BACKGROUND: The disease burden of coronary heart disease patients in Tibet, China, ranks high in the country. Due to the local culture and environment, patients with coronary heart disease have increased risk factors for the disease, and their survival is worrisome. OBJECTIVES: The purpose of this study was to determine the relationship between health literacy and quality of life for patients with coronary heart disease in Tibet, China, and to explore the mediating roles of self-efficacy and self-management. METHODS: A cross-sectional study was conducted from August 2020 to July 2021 in Tibet. A total of 258 patients with coronary heart disease in Tibet participated. Self-reported questionnaires were used to assess health literacy, self-efficacy, self-management, and quality of life. Pearson correlation analysis and the SPSS PROCESS macro were used to analyze the data. RESULTS: The mean total score for the health literacy of patients with coronary heart disease in Tibet was 3.59 ± 0.80 points, showing the existence of a limited level of literacy. The quality of life was of an average level, with scores of 57.20 ± 21.70 points and 63.63 ± 20.66 points for physical and mental status, respectively. Self-efficacy and self-management mediated the relationship between health literacy and quality of life. CONCLUSIONS: Self-efficacy and self-management mediate the relationship between health literacy and quality of life. Targeted interventions for health literacy, self-efficacy, and self-management skills are important to improve the quality of life of Tibetan patients with coronary heart disease.

Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements.

Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.