The Bidirectional Relationship of Depression and Inflammation: Double Trouble.

Мета: оновити клінічні практичні настанови щодо вродженої гіперплазії надниркових залоз унаслідок дефіциту 21-гідроксилази, що були опубліковані Ендокринним Товариством у 2010 році. Висновки: представлені оновлені рекомендації з найкращої практики щодо клінічного управління вродженою гіпер­плазією надниркових залоз на основі опублікованих даних та експертної думки з додатковими міркуваннями щодо безпеки пацієнтів, якості життя, витрат та використання (J. Clin. Endocrinol. Metab. 103: 1—46, 2018).

Вроджена гіперплазія надниркових залоз внаслідок дефіциту 21-гідроксилази. Клінічні практичні настанови Ендокринологічного Товариства. Частина 1

This paper reviews new drug targets in the treatment of depression and new drug candidates to treat depression. Depression is characterized by aberrations in six intertwined pathways: (1) inflammatory pathways as indicated by increased levels of proinflammatory cytokines, e.g. interleukin-1 (IL-1), IL-6, and tumour necrosis factor α. (2) Activation of cell-mediated immune pathways as indicated by an increased production of interferon γ and neopterin. (3) Increased reactive oxygen and nitrogen species and damage by oxidative and nitrosative stress (O&NS), including lipid peroxidation, damage to DNA, proteins and mitochondria. (4) Lowered levels of key antioxidants, such as coenzyme Q10, zinc, vitamin E, glutathione, and glutathione peroxidase. (5) Damage to mitochondria and mitochondrial DNA and reduced activity of respiratory chain enzymes and adenosine triphosphate production. (6) Neuroprogression, which is the progressive process of neurodegeneration, apoptosis, and reduced neurogenesis and neuronal plasticity, phenomena that are probably caused by inflammation and O&NS. Antidepressants tend to normalize the above six pathways. Targeting these pathways has the potential to yield antidepressant effects, e.g. using cytokine antagonists, minocycline, Cox-2 inhibitors, statins, acetylsalicylic acid, ketamine, ω3 poly-unsaturated fatty acids, antioxidants, and neurotrophic factors. These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously. Both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways. GSK-3 inhibitors have antidepressant effects in animal models of depression. Nrf2 activators and GSK-3 inhibitors have the potential to be advanced to phase-2 clinical trials to examine whether they augment the efficacy of antidepressants or are useful as monotherapy.

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

Neuroplastic changes in depression: a role for the immune system.

Part I: Basic Concepts Underlying the Microbiota-Gut-Brain Axis.- Microbial Endocrinology and the Microbiota-Gut-Brain Axis.- Utilizing "omics" Tools to Study the Complex Gut Ecosystem.- The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control.- Intestinal Barrier Function and the Brain-Gut Axis.- Vagal Pathways for Microbiome-Brain-Gut Axis Communication.- The Brain-Gut Axis in Health and Disease.- Part II: Mechanistic Factors Influencing the Microbiota-Gut-Brain Axis.- Gastrointestinal Hormones and Their Targets.- Microbiome, HPA Axis and Production of Endocrine Hormones in the Gut.- Neuropeptides and the Microbiota-Gut-Brain Axis.- Bacterial Neuroactive Compounds Produced by Psychobiotics.- Multidirectional Chemical Signalling Between Mammalian Hosts, Resident Microbiota, and Invasive Pathogens: Neuroendocrine Hormone-Induced Changes in Bacterial Gene Expression.- Influence of Stressor-Induced Nervous System Activation on the Intestinal Microbiota and the Importance for Immunomodulation.- Part III: The Microbiota-Gut-Brain Axis in Health and Disease.- The Effects of Inflammation, Infection and Antibiotics on the Microbiota-Gut-Brain Axis.- Microbiota, Inflammation and Obesity.- Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders.- Microbiota-Gut-Brain Axis and Cognitive Function.- The Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential.- Neuroimaging the Microbiome-Gut-Brain Axis.- The Future of Probiotics for Disorders of the Brain-Gut Axis.- Index.

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Microbial endocrinology : the microbiota-gut-brain axis in health and disease

Evidence indicates that there is an emerging tendency towards autoimmunity occuring in major depressive disorder (MDD). The aim of our study is to investigate the mechanism of autoimmune process in MDD from a novel insight of Th17 cells, which have been identified as the significant activators of autoimmunity. We included 40 patients with MDD and 30 healthy control subjects. An indirect immunofluorescence test was used for the detection of serum antinuclear antibodies (ANA), and revealed that the patient group was positive more frequently than the control group. By flow cytometric analysis, depressed subjects revealed a significant increase in peripheral Th17 cell number, and an obvious decrease in T-reg cell number, showing an imbalance of Th17/Treg ratio compared to healthy controls. We also found a higher level of RORγt (retinoic acid-related orphan receptor-γt, the specific transcription factor of Th17 cell) mRNA expression in peripheral blood lymphocytes by RT-PCR and serum concentration of IL-17 by ELISA in patients. In conclusion, our study showed a potential role of Th17 cells in the autoimmune process in MDD patients, thus contributing to the existing evidence of autoimmune inclination in MDD.

Emerging tendency towards autoimmune process in major depressive patients: A novel insight from Th17 cells

Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process. Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs). Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%, ) and AIA (63.6% versus 0%, ) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region. Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity.

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Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

Traditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately.The retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters.1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters.The novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications. 

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation.

Serum uric acid (SUA) is regarded as an independent risk factor for nonalcoholic fatty liver disease (NAFLD). However, the role of SUA in the new diagnosis flowchart of metabolic-associated fatty liver disease (MAFLD) remains unclear. A cross-sectional study enrolled consecutive individuals with ultrasonography and magnetic resonance imaging–based proton density fat fraction (MRI-PDFF) measurements in the First Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2021. All patients were divided into four groups according to their baseline SUA levels and sex. Of the 3537 ultrasound-diagnosed and 1017 MRI-PDFF-diagnosed MAFLD patients included, the prevalence of severe steatosis determined with ultrasound or MRI-PDFF increased across the serum SUA quartiles. The SUA cutoffs were identified as ≥478 µmol/L and ≥423.5 µmol/L for severe steatosis in male and female MAFLD, respectively. Furthermore, using these cutoff values, patients with higher SUA levels in the NAFLD–non-MAFLD group had higher liver fat contents than those without (16.0% vs. 9.7%, p < 0.001). The lean/normal-weight NAFLD–non-MAFLD patients with higher SUA levels are still at high risk of severe steatosis. This study supports the rationale for SUA being established as another risk factor for metabolic dysfunctions in lean/normal-weight MAFLD.

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The Additive Values of the Classification of Higher Serum Uric Acid Levels as a Diagnostic Criteria for Metabolic-Associated Fatty Liver Disease

Introduction Measurement of glomerular filtration rate (GFR) is critical for the diagnosis and stratification of chronic kidney disease (CKD) Recent studies have shown that cystatin C is superior to creatinine for the detection of impaired GFR, and several cystatin C-based equations for estimating GFR have been developed for this clinical application We conducted the present study to assess the applicability of cystatin C as a routine clinical laboratory index and to determine the performance of cystatin Cbased equations in estimating GFR in CKD patients in China Methods Performance evaluation of particle-enhanced turbidimetric cystatin C assay on the Abbott Aeroset analyser was carried out according to the National Committee for Clinical Laboratory document EP10-A2 Estimated GFR, which was generated from cystatin C-based equations, was compared with measured GFR, which was detected by plasma clearance of 99mTc-DTPA Results Our cystatin C assay showed a very low total imprecision and linearity drift All eight cystatin C-based GFR estimating equations underestimated or overestimated GFR as compared with GFR determined by 99mTc-DTPA clearance Conclusion Although the cystatin C assay is acceptable for routine clinical laboratory monitoring, none of the existing cystatin C-based equations were ideal for estimating GFR in Chinese CKD patients

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Performance evaluation of a particle-enhanced turbidimetric cystatin C assay using the Abbott Aeroset analyser and assessment of cystatin C-based equations for estimating glomerular filtration rate in chronic kidney disease

Yanhong Sun

Papers

Emerging tendency towards autoimmune process in major depressive patients: A novel insight from Th17 cells

Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation.

The Additive Values of the Classification of Higher Serum Uric Acid Levels as a Diagnostic Criteria for Metabolic-Associated Fatty Liver Disease

Performance evaluation of a particle-enhanced turbidimetric cystatin C assay using the Abbott Aeroset analyser and assessment of cystatin C-based equations for estimating glomerular filtration rate in chronic kidney disease