Expert opinion on therapeutic targets
-
Expert Opin. Ther. Targets · Jun 2016
Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection.
Previously, we demonstrated that sirtuin (SIRT)1 plays vital roles in the small intestine (SI), protecting against severe hemorrhagic shock (HS), and that polydatin (PD) can attenuate SI injury via SIRT1 activation. ⋯ The SIRT3-SOD2 signaling pathway is involved in mitochondrial dysfunction induced by HS. PD attenuates mitochondrial dysfunction via activation of the SIRT3-SOD2 pathway, and may be a new approach for HS treatment.
-
Expert Opin. Ther. Targets · Jan 2016
ReviewTherapeutic implications of innate immune system in acute pancreatitis.
Acute pancreatitis (AP) is an inflammatory disorder of the pancreas encompassing a cascade of cellular and molecular events. It starts from premature activation of zymogens with the involvement of innate immune system to a potential systemic inflammatory response and multiple organ failure. Leukocytes are the major cell population that participate in the propagation of the disease. Current understanding of the course of AP is still far from complete, limiting treatment options mostly to conservative supportive care. Emerging evidence has pointed to modulation of the immune system for strategic therapeutic development, by mitigating the inflammatory response and severity of AP. In the current review, we have focused on the role of innate immunity in the condition and highlighted therapeutics targeting it for treatment of this challenging disease. ⋯ The current state of knowledge on AP, limitations of presently available therapeutic approaches and the promise of therapeutic implications of innate immune system in AP are discussed.
-
Kisspeptins are a family of neuropeptides whose identification has become one of the biggest discoveries in reproductive endocrinology during the past decade. Kisspeptins act upstream of GnRH as high-level mediators of the reproductive axis. ⋯ The identification of the kisspeptin signaling pathway has greatly advanced the study of reproductive endocrinology. Building on a large body of animal data, a growing number of human studies have shown that exogenous kisspeptin can stimulate physiological gonadotropin responses in both healthy subjects and those with disorders of reproduction. There is an increasing appreciation that kisspeptin may act as a signal transmitter between metabolic status and reproductive function. Future work is likely to involve investigation of novel kisspeptin analogs and further exploration of role of neurokinin B and dynorphin on the kisspeptin-GnRH axis.
-
Expert Opin. Ther. Targets · Jul 2015
Comparative StudyPolydatin protects hepatocytes against mitochondrial injury in acute severe hemorrhagic shock via SIRT1-SOD2 pathway.
The aim of the study was to determine whether hepatocyte mitochondrial injury instigates severe shock and to explore effective therapy. ⋯ PD effectively preserved hepatocytes from mitochondrial injury via SIRT1-SOD2 pathway and may be a new approach to treatment of irreversible shock.
-
Expert Opin. Ther. Targets · Apr 2015
ReviewBrain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?
Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. ⋯ This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.