L-arginine attenuates Streptococcus uberis-induced inflammation by decreasing miR155 level.

L-arginine, as an essential substance of the immune system, plays a vital role in innate immunity. MiR155, a multi-functional microRNA, has gained importance as a regulator of homeostasis in immune cells. However, the immunoregulatory mechanism between L-arginine and miR155 in bacterial infections is unknown. Here, we investigated the potential role of miR155 in inflammation and the molecular regulatory mechanisms of L-arginine in Streptococcus uberis (S. uberis) infections. And we observed that miR155 was up-regulated after infection, accompanying the depletion of L-arginine, leading to metabolic disorders of amino acids and severe tissue damage. Mechanically, the upregulated miR155 mediated by the p65 protein played a pro-inflammatory role by suppressing the suppressor of cytokine signaling 6 (SOCS6)-mediated p65 ubiquitination and degradation. This culminated in a violently inflammatory response and tissue damage. Interestingly, a significant anti-inflammatory effect was revealed in L-arginine supplementation by reducing miR155 production via inhibiting p65. This work firstly uncovers the pro-inflammatory role of miR155 and an anti-inflammatory mechanism of L-arginine in S.uberis infection with a mouse mastitis model. Collectively, we provide new insights and strategies for the prevention and control of this important pathogen, which is of great significance for ensuring human food health and safety.

Antitumor potential of Hedyotis diffusa Willd: A systematic review of bioactive constituents and underlying molecular mechanisms.

Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the quest for more efficient and less toxic medication strategies is still at the forefront of current research. Hedyotis diffusa Willd (HDW), a Chinese herb medicine, has received great attention in the past two decades and has been well documented in clinics for antitumor activity in a variety of human cancers. This review discussed a total of 58 different kinds of active antitumor components isolated from HDW, including iridoids, flavonoids, flavonol glycosides, anthraquinones, phenolic acids, and their derivatives, sterols, and volatile oils. Their antitumor activities include inhibition of tumor cell proliferation, induction of tumor cell apoptosis and tumor angiogenesis, regulation of the host immune response, anti-inflammatory and antioxidant, and protective autophagy. Besides, we provide up-to-date and systematic evidence for HDW antitumor activities and the possible underlying molecular mechanisms and reference for further development of novel drugs and dosage formulation in control of human cancers.