miRNA contributes to neuropathic pains.

Neuropathic pain (NP) is a kind of chronic pain caused by direct injury to the peripheral or central nervous system (CNS). microRNAs (miRNAs) are small noncoding RNAs that mostly interact with the 3 untranslated region of messenger RNAs (mRNAs) to regulate the expression of multiple genes. NP is characterized by changes in the expression of receptors and mediators, and there is evidence that miRNAs may contribute to some of these alterations. In this review, we aimed to fully comprehend the connection between NP and miRNA; and also, to establish a link between neurology, biology, and dentistry. Studies have shown that targeting miRNAs may be an effective therapeutic strategy for the treatment of chronic pain and potential target for the prevention of NP.

Genistein Effects on Various Human Disorders Mediated via Nrf2 Signaling.

Genistein is a flavonoid, mostly found in soybean extract and is widely used for its antioxidant and anti-inflammatory activities. Genistein can interact with estrogen receptors due to its structural similarities to estrogen. It also inhibits protein tyrosine kinases and affects a variety of intracellular signal transductions. Genistein attenuates oxidative stress via diverse cellular mechanisms. However, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the main antioxidant regulator, potentiates genistein's antioxidant effects and reduces cell damage. Nrf2 includes of seven domains and controls the expression of the phase II antioxidant enzymes to decrease oxidative stress. In this review, we address findings related to Nrf2 signaling pathways in the context of genistein's effects on diverse human diseases.

Adipose-derived mesenchymal stem cells reduced transient cerebral ischemia injury by modulation of inflammatory factors and AMPK signaling.

Stem cell-based treatments have been recommended as a feasible therapy for stroke victims due to their potential for angiogenesis, neurogenesis, and synaptic plasticity. The intracellular mechanisms of stem cells against cerebral hypoperfusion are not well recognized. In this study, by releasing the clips, the reperfusion period was extended to 96 h, and two hours after cerebral ischemia, animals received adipose-derived MSCs. MSCs were isolated from the inguinal fat pads of rats and injected into two-vessel occlusion (2VO) rats 1 h after ischemia induction. Ninety-six hours after 2VO induction, behavioral and molecular tests were assessed. Adipose-derived MSCs treatment improves neurological scores, passive avoidance memory, and novel object recognition tests in the 2VO model compared to 2VO rats (P < 0.001). MSCs treatment decreased TNF-α (P < 0.01) and IL-6 (P < 0.01) and apoptotic factors (Bax/Bcl-2 ratio and caspase-3 level (P < 0.01)) compared with ischemic rats. MSCs treatment of ischemic rats could enhance Klotho-α and AMPK-α compared with ischemic rats (P < 0.001). The study disclosed that adipose-derived MSCs could improve neurological damage and memory deficits by reducing neuronal death in cerebral ischemia. Data proposed that adipose-derived MSCs inhibit pro-inflammatory factors such as IL-6 and TNF-α, consequently decreasing apoptosis in the hippocampus of CCAO rats. Besides, the Klotho-α and AMPK-α measurements found that MSCs might induce intracellular neuroprotective pathways via activation of Klotho-α/AMPK-α signaling.

Dimethyl fumarate protects the aged brain following chronic cerebral hypoperfusion-related ischemia in rats in Nrf2-dependent manner.

It has been stated that chronic cerebral hypoperfusion (CCH) markedly prompts neuronal damage and affects cognition. Dimethyl fumarate (DMF), a nuclear erythroid 2-related factor 2 (Nrf2) activator, represents a class of molecules exhibiting neuroprotection. We explored the effect of DMF on CCH using a model of permanent left common carotid occlusion. The left common carotid artery was occluded and then DMF (100mg.kg-1) was orally administrated three times per week for four consecutive weeks. Behavioral rests, PET imaging and Hematoxylin and Eosin staining, were examined and also, the hippocampal level of inflammatory, Nrf2 antioxidant, neuronal plasticity and apoptotic factors were determined using Western blot analysis and related ELISA kits. The neurological deficit scores were significantly reduced in the treatment group compared with the CCH group (P<0.001). DMF decreased the novel object recognition index (NOR) compared with the CCH group, while CCH + DMF increased the NOR compared with the CCH group (P<0.001). CCH + DMF reduces the ratio of Bax/Bcl2 and capase-3 activity in comparison to the CCH group (P<0.001). Treatment with DMF increased Nrf2, NAD(P)H dehydrogenase-1 and Heme oxygenase-1 and decreased Tumor necrosis factor α and Nuclear factor-κB density compared with the CCH group (P<0.001). A significant increase in brain-derived neurotrophic factor and c-fos was found in DMF-treated rats compared with the CCH group (P<0.001). Also, retinoic acid inhibits Nrf2 activation via DMF and increases inflammatory factors in hypoperfused rats' hippocampus compared with the CCH group (P<0.001). Long-term DMF treatment induces the Nrf2 pathway and has beneficial effects on memory and motility in CCH.