A Review of Sipuleucel-T in Combination with Other Therapies for Metastatic Castration-Resistant Prostate Cancer

Recent research has expanded the therapeutic landscape for sipuleucel-T by introducing several combination treatments. These include innovative hormone therapies (enzalutamide and abiraterone), immunomodulatory agents (including IL-15, IL-7, atezolizumab, ipilimumab, and indoximod), DNA vaccines, and radiopharmaceuticals, many of which have demonstrated enhanced clinical outcomes and received approval from the U.S. Food and Drug Administration (FDA). These combination therapies present novel opportunities to enhance patient survival and quality of life. Sipuleucel-T, a significant autologous cell immunotherapy, was approved by the FDA in 2010 for the treatment of patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Integration of sipuleucel-T with other therapeutic modalities holds promise for advancing mCRPC treatment. Nevertheless, the optimal sequencing and combination strategies for sipuleucel-T with other therapies remain under investigation, with numerous clinical trials currently exploring new treatment paradigms. Incorporation of these therapies, particularly to develop more effective and personalized treatment strategies, necessitates additional research. Future studies should aim to ascertain the optimal timing and sequencing of treatments and to identify biomarkers that can predict treatment responses, thereby enhancing outcomes for patients with mCRPC. This review underscores potential strategies for the integration of sipuleucel-T with other therapies and examines their therapeutic potential in mCRPC

The combination of bioactive herbal compounds with biomaterials for regenerative medicine

Regenerative medicine aims to restore the function of diseased or damaged tissues and organs by cell therapy, gene therapy, and tissue engineering, along with the adjunctive application of bioactive molecules. Traditional bioactive molecules, such as growth factors and cytokines, have shown great potential in the regulation of cellular and tissue behavior, but have the disadvantages of limited source, high cost, short half-life, and side effects. In recent years, herbal compounds extracted from natural plants/herbs have gained increasing attention. This is not only because herbal compounds are easily obtained, inexpensive, mostly safe, and reliable, but also owing to their excellent effects, including anti-inflammatory, antibacterial, antioxidative, proangiogenic behavior and ability to promote stem cell differentiation. Such effects also play important roles in the processes related to tissue regeneration. Furthermore, the moieties of the herbal compounds can form physical or chemical bonds with the scaffolds, which contributes to improved mechanical strength and stability of the scaffolds. Thus, the incorporation of herbal compounds as bioactive molecules in biomaterials is a promising direction for future regenerative medicine applications. Herein, an overview on the use of bioactive herbal compounds combined with different biomaterial scaffolds for regenerative medicine application is presented. We first introduce the classification, structures, and properties of different herbal bioactive components and then provide a comprehensive survey on the use of bioactive herbal compounds to engineer scaffolds for tissue repair/regeneration of skin, cartilage, bone, neural, and heart tissues. Finally, we highlight the challenges and prospects for the future development of herbal scaffolds toward clinical translation. Overall, it is believed that the combination of bioactive herbal compounds with biomaterials could be a promising perspective for the next generation of regenerative medicine

Pachymic acid alleviates metabolic dysfunction-associated steatotic liver disease by inhibiting ferroptosis through PPARα

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive lipid deposition in hepatocytes without a history of significant alcohol consumption. Pachymic acid (Pac), a bioactive triterpenoid from Poria cocos, has shown promise in treating MASLD due to its antioxidant and anti-inflammatory capabilities. This study aimed to elucidate the molecular impact and mechanisms of Pac in MASLD.MethodsMale C57BL/6J mice were subjected to a high-fat diet (HFD) for 8 weeks, followed by a 4 weeks treatment with the Pac. Comprehensive assessments including physiological, biochemical, and histomorphological evaluations were performed post-treatment. Transcriptomic analysis of liver samples from normal control (NC), HFD, and HFD + high-dose Pac (Pac-H) groups was conducted, with validation through Western blot, and immunofluorescence.ResultsHFD induced biochemical abnormalities and liver injury, which were significantly reversed by Pac, as evidenced by decreased plasma levels of AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), TG (Triglyceride), and TC (Total cholesterol), and reduced hepatic TG and TC levels. Pac also mitigated lipid accumulation, peroxidation, and ferroptosis. Pac modulated the expression of PPARα (Peroxisome proliferator-activated receptor α), MAPKs (Mitogen-activated protein kinases), and ferroptosis pathways, thereby ameliorating MASLD.DiscussionThe study demonstrated that Pac inhibited the MAPKs signaling pathway and reduced hepatic ferroptosis, alleviated steatosis through PPARα regulation, offering a potential therapeutic strategy for MASLD

Xie Zhuo Tiao Zhi formula ameliorates chronic alcohol-induced liver injury in mice

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020

BACKGROUND: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. METHODS: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. FINDINGS: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, INTERPRETATION: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. FUNDING: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668)

How to Detect Scale Effect of Ecosystem Services Supply? A Comprehensive Insight from Xilinhot in Inner Mongolia, China

Spatial scale plays a crucial role in the assessment and management of ecosystem services (ES), yet explicit information for identifying and understanding the scale effect on ES supply remains limited. In an attempt to detect scale effect on ES supply from a comprehensive perspective, this study developed a framework for integrating scale effect in three aspects, including individual ES patterns, pairwise ES interactions, and ecosystem service bundles (ESB). The framework was tested in Xilinhot, a prairie landscape city of Inner Mongolia, at four different levels of spatial scale. The results indicated that, most ES showed a decreasing clustering at coarser scales in terms of spatial pattern. At the same time, coarser scales resulted in fewer trade-offs and stronger synergies between pairwise ES. The identification of ESB varied greatly with scale, and this change reflected in the composition of ES variables and spatial distribution of bundles. We attributed the scale effect of the above three aspects to differences in social-ecological factors and their driving mechanisms at different scales. This comprehensive framework could support local managers to coordinate the management of multiple ES at different scales

Ecosystem Services and Their Relationships in the Grain-for-Green Programme—A Case Study of Duolun County in Inner Mongolia, China

Grassland restoration projects are currently being implemented to mitigate human disturbance to the natural environment and reduce grassland degradation. China’s Grain-for-Green Programme (GFGP), including one project implemented in Duolun County, China, in 2000, has significantly improved the overall ecological health of this region. Using a modeling approach, this study quantified changes in four ecosystem services (ESs), including Net Primary Production (NPP), soil conservation (SC), water yield (WY), and sandstorm prevention (SP), in Duolun County between 2000 and 2016. We found the total NPP, water yield, and soil conservation increased by 80.44%, 248.2%, and 12.2%, respectively, during this period, while the sandstorm prevention decreased by 55.9%. Unlike other areas of GFGP implementation, the improvement of the ecological environment in Duolun County is largely attributed to the increased of vegetation coverage (88%) instead of land use circulation (12%). We found the grassland is a factor that reduces the trade-off while this effect was related with the grassland coverage. Future policies should be based on the mechanisms of vegetation underlying the ESs change and the relationships of ESs in order to achieve sustainable provision of ESs