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Dairy processing provides acceptable safety and shelf-life to final products, and improves their bioactivity. The present study evaluated the potential of different milk processing techniques to improve the antioxidant and angiotensin-I converting enzyme (ACE)-inhibitory activity of Cheddar cheese, during ripening. Cheese was made from milk subjected to different pre-treatments (C = untreated control, US-1 = ultrasonication, specific energy = 23 J/g, 20 kHz frequency; US-2 = Ultrasonication specific energy = 41 J/g, 20 kHz; HPP = high-pressure processing, 400 MPa for 15 min, at temperature < 40 °C; MW = microwave, temperature<40 °C, specific energy = 86.5 J/g) and analysed after ripening for 0, 3, 6 and 9 months. The results showed that the rate of proteolysis during both cheese making and subsequent ripening was significantly affected by the pre-treatment. Antioxidant activity and ACE-inhibitory potential of …