Cancer is a global problem with no sign that incidences are reducing. The great costs associated with curing cancer, through developing novel treatments and applying patented therapies, is an increasing burden to developed and developing nations alike. These financial and societal problems will be alleviated by research efforts into prevention, or treatments that utilise off-patent or repurposed agents. Phytosterols are natural components of the diet found in an array of seeds, nuts and vegetables and have been added to several consumer food products for the management of cardio-vascular disease through their ability to lower LDL-cholesterol levels. In this review, we provide a connected view between the fields of structural biophysics and cellular and molecular biology to evaluate the growing evidence that phytosterols impair oncogenic pathways in a range of cancer types. The current state of understanding of how phytosterols alter the biophysical properties of plasma membrane is described, and the potential for phytosterols to be repurposed from cardio-vascular to oncology therapeutics. Through an overview of the types of biophysical and molecular biology experiments that have been performed to date, this review informs the reader of the molecular and biophysical mechanisms through which phytosterols could have anti-cancer properties via their interactions with the plasma cell membrane. We also outline emerging and under-explored areas such as computational modelling, improved biomimetic membranes and ex vivo tissue evaluation. Focus of future research in these areas should improve understanding, not just of phytosterols in cancer cell biology but also to give insights into the interaction between the plasma membrane and the genome. These fields are increasingly providing meaningful biological and clinical data but iterative experiments between molecular biology assays, biosynthetic membrane studies and computational membrane modelling improve and refine our understanding of the role of different sterol components of the plasma membrane.
The optimal flap cover for managing open lower limb fractures is debated. Most studies have reported on surgical outcome but clinical outcome is not well recognised. We aimed to determine whether there are differences in patient-reported quality of life (QoL) outcome between local flap versus free flap.All patients admitted with lower limb open fractures were retrospectively reviewed. Patient notes were assessed for demographics, time to fracture union, wound healing and patient-reported QoL with EQ-5D-5L alongside a novel flap assessment tool.A total of 40 patients had flap reconstruction of their lower limb injury; 23 local flap (Group I) and 17 free flap (Group II). Average length of follow-up was 33.8 months. Group I -10 revisions of flaps (43.5%) and 14 surgical complications (60.9%). Fracture union was 171 days and wound healing 130 days. EQ-5D index and EQ-VAS scores were 0.709 and 79.3, respectively. Group II -8 revision of flaps (47.1%) and 12 surgical complications (70.6%). Fracture union was 273 days and wound healing 213 days. EQ-5D index and EQ-VAS scores were 0.525 and 57.2, respectively. Aesthetic appeal -48% Group I vs. 66% Group II. Significant differences were found between the two flap groups with higher scores for daily living in Group I (p = 0.007) compared to higher overall flap ratings in Group II (p = 0.049). Both groups were comparable in terms of complications; while flap congestion and dehiscence were more common with free flaps statistical interrogation did not elicit significance (p > 0.05).Local flap and free flap techniques offer distinct advantages. Local flaps have better surgical outcome and patient-reported QoL in the first few years post soft tissue reconstruction. Differences between local and free reconstructive techniques in terms of patient health and function are ameliorated in the longer term.
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