Int. J. Transl. Med., Volume 4, Issue 2 (June 2024) – 8 articles

Gamma knife radiosurgery (GKRS), a form of stereotactic radiosurgery (SRS), has gained importance in treating glioblastoma alongside conventional chemotherapy. This study aims to assess the efficacy of combining GKRS with surgery and chemotherapy to enhance treatment outcomes for glioblastoma patients. This prospective clinical study, adhering to STROBE guidelines, assessed 121 glioblastoma patients from June 2008 to December 2022. All patients who had not undergone prior radiotherapy underwent open surgical tumor resection, GKRS, and adjuvant chemotherapy. In the analyzed cohort, the median survival post-diagnosis was 21.2 months (95% CI: 11.4–26.7) and the median progression-free survival was 13.6 months (95% CI: 12.5–28.3). The median time to first recurrence post-treatment was 14.5 months (range: 4–33 months). The median prescribed dose for GKRS was 12 Gy (range: 10–17 Gy), with a median target volume of 6.0 cm³ (range: 1.6–68 cm³). Post GKRS, 92 patients experienced local recurrence, 21 experienced distant recurrence, and 87 received additional treatment, indicating diverse responses and treatment engagement. This study evaluates the use of GKRS for glioblastomas, emphasizing its efficacy and complications in a single-center trial. It suggests integrating GKRS into initial treatment and for recurrences, highlighting the comparable survival rates but underscoring the need for further research. Full article

In accordance with the usage of Euonymus alatus (EA) as folk medicine in diabetes, the present study employed water and 70% ethanol twig extract to assess its antidiabetic effects in C57BL/KsJ-db/db mice. These effects were then compared with those observed in normal C57BL/6J Jms Slc mice. After 4 weeks of supplementation with 70% ethanolic EA extract or water EA extract by oral gavage at a dose of 500 mg/kg with distilled water (DW) per day, body weight was measured and compared with the diabetic group (Db). HPLC demonstrated that the maximum flavonoids were extracted in the Et.EA extract rather than in the water EA extract. The supplementation of the Et.EA extract significantly increased liver and muscle glycogen content with respect to the Db group. Additionally, the Et.EA extract modulated the expression of glycogen synthase (GS) in the liver and muscles of Db mice, indicating that it plays a promotive role in glycogen synthesis. Mechanistically, Et.EA extract activates insulin receptor substrate (IRS1/IRS2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) in the liver and muscles of Db mice. In conclusion, Et.EA extract attenuates insulin resistance by regulating the expression of metabolic enzymes and signaling pathways. Full article

In the context of the contemporary accelerated pace of life, emphasizing the importance of sleep quality is essential for enhancing overall well-being and health. Historically underestimated, recent studies highlight sleep’s vital importance for physical, mental, and emotional well-being. Chronic sleep deprivation is connected to numerous health problems such as cardiovascular disease, diabetes, and weakened immune response. Additionally, lack of sleep can worsen stress, depression, and anxiety, impairing daily life and overall quality of life. This study investigates the link between poor sleep quality and key factors affecting wellness, such as mental health and eating disorders. Through a cross-sectional analysis involving 407 participants, utilizing established measures including the Depression Anxiety Stress Scale (DASS-21), the Eating Disorder Examination Questionnaire Short (EDE-QS), and the single-item Sleep Quality Scale (SQS), data were collected and analyzed using SPSS v28 and R-Statistics. The findings reveal a significant correlation (p < 0.05) between DASS-21, EDE-QS, and SQS, indicating that individuals experiencing poor sleep quality exhibit higher levels of depression, anxiety, and stress. Furthermore, multinomial logistic regression analysis highlights low sleep quality as a risk factor for both mental health (OR: 1.071, 95% CI: 1.042, 1.102, p < 0.05, low vs. high sleep quality) and eating disorders (OR: 1.047, 95% CI: 1.004, 1.092, p < 0.05, low vs. high sleep quality). Overall, these results underscore the critical role of sleep quality in mental health and suggest that insomnia is a predictive factor for both poor mental well-being and disordered eating habits. The main contribution of this study is its identification of poor sleep quality as a common risk factor linking mental health issues and eating disorders, which emphasizes the need for integrated treatment strategies focusing on sleep improvement. Further research through randomized controlled trials is warranted to validate the findings of this cross-sectional study. Full article

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and ¹H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found. Full article

After an initial positive response to chemotherapy, cancer patients often acquire chemoresistance and tumor relapse, which makes cancer one of the most lethal diseases worldwide. Exosomes are essential mediators of cell-to-cell communication by delivering their cargo, such as proteins, RNAs and DNA, from cell to cell. They participate in cancer progression, metastasis, immune response and therapy resistance. Their ability to shuttle between cells makes them efficient drug delivery systems. As drug transporters, they provide novel strategies for cancer therapy by advancing targeted drug therapy and improving the therapeutic effects of anti-cancer medications. In this review, a comprehensive overview of the potential of exosomes as therapeutic agents and targeted molecules in the treatment of cancer patients is given. The current challenges of preparation of exosomes loaded with drugs and delivering them to the recipient tumor cells as well as a consequent exosome-mediated cancer therapy are also discussed. Full article

Cross-sectional and longitudinal profiling of full sets of nucleic acids, peptides, or proteins as well as metabolites expressed in biospecimens acquired via a cardiovascular disease-oriented biobank may aid in the elucidation of the disease pathways and mechanisms underlying individual cardiovascular diseases, such as degenerative valvular heart disease. This may promote the development of novel and effective, personalized diagnostic and therapeutic strategies to efficiently reduce cardiovascular mortality and morbidity as well as its health and economic burden. This brief report aims to describe the unique, standardized, interdisciplinary, and interprofessional approach to cross-sectional and longitudinal cardiovascular biobanking and databasing at the University Hospital Augsburg. Moreover, we present the study protocol of a specific, well-defined, prospective, single-center research project involving cross-sectional and longitudinal cardiovascular biobanking. The aim of this project is to gain a better insight into the molecular mechanisms underlying aortic valve disease-induced cardiomyopathy and the long-term effect of surgical correction of the aortic valve pathology on the left ventricular myocardial molecule profile. Full article

The NLRP3 inflammasome is an important mediator of the host inflammatory response, and downregulation of inflammation is important in cancer treatment. Here, we investigated four different pancreatic ductal adenocarcinoma (PDAC) cell lines, AsPC-1, BxPC-3, CFPAC-1 and Panc-1, with regards to NLRP3 inflammasome formation and cytokine secretion. ASC specks were observed in all the cell lines investigated, but AsPC-1 was the only cell-line with the co-localization of anti-ASC and anti-NLRP3 and spontaneously formed multiple NLRP3 inflammasomes per cell. The co-localization of NLRP3 and ASC was not accompanied by IL-1β release nor significant IL-18 release. BxPC-3 displayed relatively high expression of the inflammasome-related genes IL1B and CASP1 and had the highest levels of IL1β and IL18 secretion and the highest amount of ASC. The inflammasome-associated genes IL18 and PYCARD were up-regulated in the PDAC primary tumors compared to normal tissue, and high PDAC tumor expression of IL18, CASP1 and PYCARD correlated with low patient survival. We have shown that PDAC cell lines display significant variations in their inflammasome-related gene expression and readouts. We conclude that spontaneous ASC speck formation is possible in PDAC cells and that multiple NLRP3 inflammasomes are formed spontaneously in AsPC-1 cells but that the co-localization of NLRP3 and ASC specks does not automatically entail inflammasome function. Full article

The liver is structurally organized into zonation, where Liver Sinusoidal Endothelial Cells (LSECs) play a crucial role during chronic liver injury and the early stages of fibrosis. Fibrosis can be reversed if diagnosed early at the molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in a normal and diseased fibrotic human liver. DGE analysis was performed over LSECs, and we identified the top 20 expressed genes in the periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells showed OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, and CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, and CTSL genes as expressed in DILI and NASH EC populations. The connection between LSEC marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases. Full article