The present review aimed to systematically review skin toxicity changes following breast cancer radiotherapy (RT) using ultrasound (US). PubMed and Scopus databases were searched according to PRISMA guidelines. The characteristics of the selected studies, measured parameters, US skin findings, and their association with clinical assessments were extracted. Seventeen studies were included with a median sample size of 29 (range 11-166). There were significant US skin changes in the irradiated skin compared to the nonirradiated skin or baseline measurements. The most observed change is skin thickening secondary to radiation-induced oedema, except one study found skin thinning after pure postmastectomy RT. However, eight studies reported skin thickening predated RT attributed to axillary surgery. Four studies used US radiofrequency (RF) signals and found a decrease in the hypodermis's Pearson correlation coefficient (PCC). Three studies reported decreased dermal echogenicity and poor visibility of the dermis-subcutaneous fat boundary (statistically analysed by one report). The present review revealed significant ultrasonographic skin toxicity changes in the irradiated skin most commonly skin thickening. However, further studies with large cohorts, appropriate US protocol, and baseline evaluation are needed. Measuring other US skin parameters and statistically evaluating the degree of the association with clinical assessments are also encouraged.
We evaluated the acute (single-dose) and subacute (repeated-dose) oral toxicity of alcalase-hydrolyzed whey protein concentrate. Our acute study revealed no death or treatment-related complications, and the median lethal dose of whey protein concentrate hydrolysate was >2,500 mg/kg. In the subacute study, when the hydrolysate was fed at 3 different concentrations (200, 400, and 800 mg/kg), no groups showed toxicity changes compared with controls. Then, whey protein concentrate hydrolysate was orally administered to spontaneously hypertensive rats. Results revealed significant reductions in blood pressure in a dose-dependent manner, and dosing at 400 mg/kg led to significant blood pressure reduction (-47.8 mm Hg) compared with controls (blood pressure maintained) and the findings of previous work (-21 mm Hg). Eight peptides-RHPEYAVSVLLR, GGAPPAGRL, GPPLPRL, ELKPTPEGDL, VLSELPEP, DAQSAPLRVY, RDMPIQAF, and LEQVLPRD-were sequentially identified and characterized. Of the peptides, VLSELPEP and LEQVLPRD showed the most prominent in vitro angiotensin-I converting enzyme inhibition with half-maximal inhibitory concentrations of 0.049 and 0.043 mM, respectively. These findings establish strong evidence for the in vitro and in vivo potential of whey protein concentrate hydrolysate to act as a safe, natural functional food ingredient that exerts antihypertensive activity.