Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Food allergy and food‐based therapies in neurodevelopmental disorders

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided.     

The microbiota-gut-brain axis in functional gastrointestinal disorders

Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.     

Glucagon-like Peptide 1 (7-36 hide) Secretion in Response to Luminal Sucrose from the Upper and Lower Gut: A Study Using α-Glucosidase Inhibition (Acarbose)

Background: After nutrient ingestion there is an early response of glucagon-like peptide 1 (GLP-1) immunoreactivity, although GLP-1 is mainly produced in endocrine cells from the lower gut (ileum and colon/rectum), suggesting that indirect stimulation is important after the ingestion of carbohydrates that are predominantly absorbed from the upper intestine.

Methods: To enable contact of sucrose with lower gut mucosa, sucrose was administered by mouth with and without the simultaneous ingestion of 100mg of the α-glucosidase inhibitor acarbose to six normal healthy volunteers.

Results: There was an early increment in GLP-1 15min after sucrose ingestion. With acarbose, sucrose reached the colon approximately 120min after ingestion, as indicated by an increment in breath hydrogen exhalation (p < 0.0001), and GLP-1 release was prolonged (p < 0.0001). The sucrose-related increments in glucose, insulin, C-peptide, and gastric inhibitory polypeptide (GIP) and the suppression of glucagon were only marginally affected by acarbose administration.

Conclusions: GLP-1 release appears to be influenced by indirect mechanisms (early response after sucrose) and by direct luminal contact with lower gut mucosal endocrine cells (late response with acarbose).     

Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.     

BMPs and Chordin regulate patterning of the directive axis in a sea anemone

The TGF-β molecules Dpp/BMP2/4/7 and their antagonist Sog/Chd play a conserved role in establishing the dorso-ventral (DV) axis in bilaterians. Homologues of BMPs and the antagonist, Chordin, have been isolated from Cnidaria and show a striking asymmetric expression pattern with respect to the primary oral-aboral (OA) axis. We used Morpholino knockdowns of Nematostella dpp (bmp2/4), bmp5-8, chordin, and tolloid to investigate their function during early development of the sea anemone Nematostella vectensis. Molecular analysis of the BMP Morpholino phenotypes revealed an upregulated and radialized expression of bmps and chordin in ectoderm and endoderm indicating a negative feedback loop. Our data further suggest that BMP signaling is required for symmetry breaking of bmp and chordin expression during gastrulation. While bmps and chordin marker genes of the ectodermal OA axis extended aborally, other ectodermal markers of the OA axis were not significantly affected. By contrast, expression of other endodermal marker genes marking both the OA and the directive axis were abolished. Our data suggest that the logic of BMP2/4 signaling and the BMP antagonist, Chordin, differs significantly between Cnidaria and Bilateria, yet the double negative feedback loop detected in Nematostella bears systemic similarities with part of the regulatory network of the DV axis patterning system in amphibians.     

严重感染患者下丘脑-垂体-肾上腺轴功能的再评价

应用化学免疫发光法分组测定10例严重全身性感染（危重组）和12例感染性休克（休克组）患者在病程早期（确诊后1，3，5d）血清皮质醇和血浆ACTH水平，与12例对照组患者进行对照分析；并进行1μg ACTH刺激试验评价严重感染患者下丘脑-垂体-肾上腺（HPA）轴功能。结果显示，与对照组相比，危重组的ACTH明显升高（P〈0．05），休克组的ACTH明显降低（P〈0．05），ACTH与严重感染患者的病情危重程度密切相关（P〈0．05），在存活组和死亡组间存在显著差异（P〈0．05）。提示HPA轴在严重感染发生早期已经出现功能改变，ACTH水平与严重感染患者的病情危重程度及住院病死率密切相关。