BACKGROUND AND PURPOSE Protective mechanisms of the endogenous cannabinoid (eCB) system against drug-induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation. EXPERIMENTAL APPROACH The 2-arachidonoyl glycerol (2-AG)-related signaling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg kg-1 day-1 ) of acetaminophen (APAP), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg/kg), or lacking CB1 and CB2 receptors. KEY RESULTS Acute APAP increased the expression of CB2, ABHD6 and COX-2, while repeated APAP increased that of CB1 and COX-2 and decreased that of DAGLβ. Both acute and repeated APAP decreased the liver content of acylglycerols (2-AG, 2-LG, 2-OG).  https://www.selleckchem.com/products/gpna.html  Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute APAP-exposed CB2ko mice had higher expression of the fibrogenic αSMA and the cytokine IL6, and lower apoptotic cleaved Caspase3. CB1 deficiency enhanced the repeated APAP-induced increases in αSMA and cleaved Caspase3, and blocked those of Cyp2e1, TNFα, the chemokine MCP1, and the circulating transaminase γGT. Although JWH015 reduced the expression of αSMA and TNFα in acute APAP, ACEA increased the expression of cleaved Caspase3 and MCP1 in repeated APAP. CONCLUSIONS AND IMPLICATIONS The differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to APAP-induced hepatotoxicity should be considered for designing alternative therapies against DILI. This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE DMSO has been found to promote tissue repair. However, the role of DMSO in diabetic skin wound healing and the underlying molecular mechanisms are still unclear. EXPERIMENTAL APPROACH The effects of DMSO on wound healing were evaluated by HE staining, immunohistochemistry, and collagen staining using a wound model of full-thickness skin resection on the backs of nondiabetic or diabetic mice. Real-time cell analysis and 5-ethynyl-2´-deoxyuridine incorporation assays were used to study the effect of DMSO on primary fibroblast proliferation. A transwell assay was used to investigate keratinocyte migration. The associated signalling pathway was identified by western blotting and inhibitor blocking. The effect of DMSO on the translation rate of downstream target genes was studied by RT-qPCR of polyribosome mRNA. KEY RESULTS We found that low-concentration DMSO significantly accelerated skin wound closure by promoting fibroblast proliferation in both nondiabetic and diabetic mice. In addition, increased migration of keratinocytes may also contribute to accelerated wound healing, which was stimulated by increased TGF-β1 secretion from fibroblasts. Furthermore, we demonstrated that this effect of DMSO depends on AKT/mTOR-mediated translational control and the promotion of the translation of a set of cell proliferation-related genes. As expected, DMSO-induced wound healing and cell proliferation were impaired by rapamycin, an inhibitor of AKT/mTOR signalling. CONCLUSION AND IMPLICATIONS DMSO can promote skin wound healing in diabetic mice by activating the AKT/mTOR pathway. Low-concentration DMSO presents an alternative medication for chronic cutaneous wounds, especially for diabetic patients. This article is protected by copyright. All rights reserved.Adipose tissue is an active metabolic organ that contributes to processes such as energy storage and utilization and to the production of a number of metabolic agents, such as adipokines, which play a role in inflammation. In this review, we try to elucidate the connections between peripheral inflammation at obesity and Type 2 diabetes and the central inflammatory process. Multiple lines of evidence highlight the importance of peripheral inflammation and its link to neuroinflammation, which can lead to neurodegenerative diseases such as dementia, Alzheimer's disease (AD) and Parkinson's disease. In addition to the accumulation of misfolded amyloid beta (Aβ) peptide and the formation of the neurofibrillary tangles of hyperphosphorylated tau protein in the brain, activated microglia and reactive astrocytes are the main indicators of AD progression. They were found close to Aβ plaques in the brains of both AD patients and rodent models of Alzheimer's disease-like pathology. Cytokines are key players in pro- and anti-inflammatory processes and are also produced by microglia and astrocytes. The interplay of seemingly unrelated pathways between the periphery and the brain could, in fact, have a common denominator, with inflammation in general being a key factor affecting neuronal processes in the brain. An increased amount of white adipose tissue throughout the body seems to be an important player in pro-inflammatory processes. Nevertheless, other important factors should be studied to elucidate the pathological processes of and the relationship among obesity, Type 2 diabetes and neurodegenerative diseases. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.A new coronavirus, referred to as SARS-CoV-2, is responsible for the recent outbreak of severe respiratory disease. This outbreak first detected in Wuhan, China in December 2019, has spread to other regions of China and to 25 other countries as of January, 2020. It has been known since the 2003 SARS epidemic that the receptor critical for SARS-CoV entry into host cells is the angiotensin-converting enzyme 2 (ACE2). The S1 domain of the spike protein of SARS-CoV attaches the virus to its cellular receptor ACE2 on the host cells. We thought that it is timely to explain the connection between the SARS-CoV, SARS-CoV-2, ACE2 and the rationale for soluble ACE2 as a potential therapy. © 2020 The Author(s).BACKGROUND Microvascular decompression (MVD) represents a milestone for the treatment of trigeminal neuralgia (TN). Nevertheless, several complications still occur and may negatively affect the outcome. We recently proposed some technical nuances for complication avoidance related to MVD. OBJECTIVE To verify the efficacy of the proposed refinement of the standard MVD technique in terms of resolution of the pain and reduction of complication rates. METHODS We analyzed surgical and outcome data of patients with TN using a novel surgical refinement to MVD, over the last 4 yr. Outcome variables included pain relief, facial numbness, muscular atrophy, local cutaneous occipital and temporal pain or numbness, cerebellar injury, hearing loss, cranial nerve deficits, wound infection, and cerebrospinal fluid (CSF) leak. Overall complication rate was defined as the occurrence of any of the aforementioned items. RESULTS A total of 72 consecutive patients were enrolled in the study. Pain relief was achieved in 91.6% and 88.