The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity.

The sympathetic nervous system maintains metabolic homeostasis by orchestrating the activity of organs such as the pancreas, liver, and white and brown adipose tissues. From the first renderings by Thomas Willis to contemporary techniques for visualization, tracing, and functional probing of axonal arborizations within organs, our understanding of the sympathetic nervous system has started to grow beyond classical models. In the present review, we outline the evolution of these findings and provide updated neuroanatomical maps of sympathetic innervation. We offer an autonomic framework for the neuroendocrine loop of leptin action, and we discuss the role of immune cells in regulating sympathetic terminals and metabolism. We highlight potential anti-obesity therapeutic approaches that emerge from the modern appreciation of SNS as a neural network vis a vis the historical fear of sympathomimetic pharmacology, while shifting focus from post- to pre-synaptic targeting. Finally, we critically appraise the field and where it needs to go.

Placebo's invisible brother: a restricted scoping review of the biomedical literature on the nocebo effect.

ABSTRACT: Placebos and their beneficial clinical and psychological effects are well-researched, but nocebo effects receive far less attention, despite being highly undesirable. The aim of this restricted scoping review was to examine how nocebo effects are represented in the biomedical literature and to identify the trends and gaps in existing knowledge. After searching 5 biomedical databases and 2 clinical trials registries (from their inception to December 23, 2020) for articles on nocebo effects or negative placebo effects, 1161 eligible publications were identified. The 2 main publication types were nonsystematic reviews (37.7%) and primary research studies (35.6%); only 85 publications (7.3%) were systematic reviews and meta-analyses. The nonsystematic reviews, many of them heavily opinion-based, may contribute to the amplification of narratives, attitudes, and beliefs about nocebo effects that do not objectively reflect the primary research. The primary research articles often used nocebo effects to explain results, rather than as the primary phenomenon under investigation. Most publications were concerned with both positive and negative placebo effects, rather than just nocebo effects. Over half of the abstracts were in the field of neurology, psychiatry, psychology, or neuroscience (52.8%). The nocebo effect was most frequently investigated in the context of pain. Studies were almost exclusively in adults and more often in healthy participants than in patients. In conclusion, in the biomedical literature, there is an overabundance of nonsystematic reviews and expert opinions and a lack of primary research and high-quality systematic reviews and meta-analyses specifically dealing with nocebo effects.

Expression of proteins upregulated in hepatocellular carcinoma in patients with alcoholic hepatitis (AH) compared to non-alcoholic steatohepatitis (NASH): An immunohistochemical analysis of candidate proteins.

Both non-alcoholic steatohepatitis (NASH) and alcoholic hepatitis (AH) can lead to cirrhosis and hepatocellular carcinoma. However, the rate of progression to cirrhosis and tumorigenesis in AH is greater than that in NASH. We asked whether there are differences between the two conditions in the expression levels of proteins involved in the pathogenesis of hepatocellular carcinoma. The proteins tested were presented at the 2017 American Association for the Study of Liver Diseases (AASLD) Liver Meeting as overexpressed in hepatocellular carcinoma: KLF4, SCL19A1, FANCG, HRH-1, DNMT1, DNMT3B, TNFR2, DUSP4, EGFR, Integrin α6, HDACII, PDE3A, BCL-XL, and MTCO2. The expression of these proteins was measured in liver biopsy sections from NASH and AH patients using immunohistochemical staining with fluorescent antibodies and then quantifying the fluorescence intensity morphometrically. In AH patients, levels of all tested proteins except HRH-1 were elevated compared to normal patients. In NASH patients, KLF4, SCL19A1, FANCG, HDACII, BCL-XL levels were increased compared to normal controls while HRH-1, DNMT1 and PDE3A levels were decreased. The relative expression of all proteins studied except BCL-XL was significantly higher in AH compared to NASH. In conclusion, proteins involved in hepatocellular cancer development are more highly expressed in AH compared to NASH and normal liver, which corresponds with the higher rate of tumorigenesis in AH patients compared to NASH patients.