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Background: Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia. Methods: For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5′- (α, β-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis. Results: Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response. Conclusion: The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase. [ABSTRACT FROM AUTHOR]

To investigate the potential protective effect of intermittent cold stimulation on lung tissues of broilers exposed to acute cold stress (ACS). A total of 384 one-day-old broilers were assigned to 4 experimental groups with 6 replicates of 16 birds each: control (CON) and ACS groups were reared at normal feeding temperature from d 1 to 42; cold treatment groups (CS3+ACS and CS9+ACS) were reared, respectively, at 3°C or 9°C for 5 h on alternate days below the CON group from d 15 to 35. Animals in CS3+ACS, CS9+ACS, and ACS groups were exposed at 10°C for 24 h on d 43. Subsequently, lung tissues were collected to perform histopathological examination and measurement of relevant indexes. The results showed that lung tissues in CS9+ACS and ACS groups exhibited increased inflammatory cell infiltrates and collagen deposition compared to the CON group, while this pathological phenomenon was less pronounced in the CS3+ACS group. Compared to CON group, H 2 O 2 and MDA contents were increased, and the activities of antioxidant enzymes (CAT, SOD, GPx, T-AOC) were reduced in CS9+ACS and ACS group (P < 0.05); mRNA and protein levels of inhibitor of NF-κB, Smad7, matrix metallopeptidase (MMP)-2, MMP9, and antioxidant-related genes were downregulated, whereas mRNA and protein levels of genes related to NF-κB/NLRP3 pathway-regulated inflammation and TGF-β1/Smad pathway-regulated fibrosis were upregulated in cold-stressed broilers (P < 0.05). mRNA levels of heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and MMP9 were increased in CS3+ACS group (P < 0.05). Moreover, the expression of most antioxidant-related genes was increased, and that of inflammation- and fibrosis-related genes was reduced in CS3+ACS group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to pulmonary fibrosis in broilers, whereas intermittent mild cold stimulation at 3°C below normal rearing temperature alleviated fibrosis by inhibiting the TGF-β1/Smad pathway modulated by the Nrf2/HO-1 and NF-κB/NLRP3 signaling pathway. This study suggests that intermittent mild cold stimulation can be a potential strategy to reduce ACS-induced lung damage in broilers. [ABSTRACT FROM AUTHOR]