Targets, Volume 2, Issue 2 (June 2024) – 4 articles

Fibrosarcoma represents a significant challenge in oncology, characterized by high invasiveness and a poor prognosis. Gelatinases, particularly matrix metalloproteinases MMP-2 and MMP-9, play a pivotal role in the degradation of the extracellular matrix, facilitating tumor invasion and metastasis. Inhibiting these enzymes has emerged as a promising therapeutic strategy. This review evaluates the progress in the development and therapeutic potential of gelatinase inhibitors as treatments for fibrosarcoma over the last decade, highlighting molecular mechanisms and future directions. A comprehensive literature review was conducted, focusing on studies published from 2013 to 2023. Research articles and review papers relevant to gelatinase inhibition and fibrosarcoma were examined to assess the efficacy and mechanisms of gelatinase inhibitors. Gelatinase inhibitors have shown the potential to reduce tumor progression, invasion, and metastasis in fibrosarcoma. Clinical trials, although limited, have indicated that these inhibitors can be effectively integrated into existing therapeutic regimens, offering a reduction in metastatic spread and potentially improving patient survival rates. Mechanistic studies suggest that the inhibition of MMP-2 and MMP-9 disrupts critical pathways involved in tumor growth and cell invasion. Gelatinase inhibition represents a viable and promising approach to fibrosarcoma treatment. Future research should focus on developing more specific inhibitors, understanding long-term outcomes, and integrating gelatinase inhibition into multimodal treatment strategies to enhance efficacy. Full article

This study aimed to investigate whether non-fasting plasma triglycerides were associated with diabetes mortality. It included 7312 US adult participants. Diabetes mortality data were obtained via the linkage to National Death Index (NDI) records. Hazard ratios of non-fasting plasma triglycerides for diabetes mortality were assessed using Cox proportional hazards models, adjusting for age, gender, ethnicity, obesity, poverty–income ratio, education levels, physical activity, alcohol consumption, cigarette smoking status, survey period, hypercholesterolemia, hypertension, diabetes, and family history of diabetes. Among these participants, 1180 had diabetes. A total of 420 diabetes-caused deaths were recorded during a mean follow-up of 16.8 years. A 1-natural-log-unit increase in non-fasting plasma triglycerides was associated with a 41% higher diabetes mortality risk (hazard ratio, 1.41; 95% confidence interval, 1.19–1.67). Participants with non-fasting plasma triglycerides in the highest quintile, versus those in the lowest quintile, had a 141% higher diabetes mortality risk (hazard ratio, 2.41; 95% confidence interval, 1.46–3.97). The positive association of non-fasting plasma triglycerides with diabetes mortality was independent of diabetes status at the baseline. In conclusion, this study demonstrated that non-fasting plasma triglycerides were positively associated with diabetes mortality, independent of diabetes status at baseline. Non-fasting triglycerides may be a therapeutic target for diabetes-related complications. Full article

Background: Staphylococcus aureus is a leading cause of skin and bloodstream infections in humans. Antibiotic resistant strains of S. aureus continue to be a problem in treating patients that are infected, so treatment options are needed. A drug discovery project identified SK-03-92 as a novel anti-staphylococcal drug, but the SK-03-92 mechanism of action is unknown. We hypothesized that a lethal factor was being released by the bacteria that killed siblings. Methods: In this study, filtration through molecular weight cut-off filters as well as boiling, trypsin treatment, and proteinase K treatment were used to ascertain what the lethal factor was released by SK-03-92 treated S. aureus cells. Results: Filtration through molecular weight cut-off filters demonstrated the lethal factor released by SK-03-92 treated S. aureus cells had a molecular cut-off between 10,000 Da and 30,000 Da that killed fresh S. aureus cells but was not released by untreated cells. Through proteinase K digestion, trypsin digestion, and boiling experiments, the lethal factor was shown to be a protein. Further experiments are needed to identify what proteins released following SK-03-92 treatment cause the death of S. aureus cells. Conclusions: The data show that SK-03-92 treatment causes S. aureus to release a lethal factor protein that kills S. aureus cells, suggesting a new mechanism of action for an antibacterial drug. Full article

Honey has become popular as a potential treatment for several ailments, including cancer. Honeys from different parts of the world have been shown to have different anti-proliferative, immune-modulatory, and anti-inflammatory actions. Yemeni Sidr honey (YSH) is world-renowned for its anti-inflammatory activity and has been suggested to have anti-cancer activity, although empirical evidence is lacking. We tested three YSH samples by HPLC to show they contained similar sugars and an overlapping group of phenolic and flavonoid components, as described previously. YSH’s apoptotic and anti-proliferative activities were measured in in vitro models of cancer growth. The treatment of breast cancer cell lines (MDA-MB-231 and MCF-7), a cervical cancer cell line (HeLa), and mouse melanoma cells (B16-BL6) with 1% (w/v) YSH in media for 48–72 h almost completely inhibited cell proliferation and promoted cell apoptosis. In contrast, a non-malignant HBL-100 cell line was more resistant to treatment with YSH. This suggests that YSH may be a good candidate as an anti-cancer treatment, which requires further study. Full article