Stress-sensitive neural circuits change the gut microbiome via duodenal glands.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis.

An Amygdalar-Vagal-Glandular Circuit Controls the Intestinal Microbiome.

Psychological states can regulate intestinal mucosal immunity by altering the gut microbiome. However, the link between the brain and microbiome composition remains elusive. We show that Brunner's glands in the duodenal submucosa couple brain activity to intestinal bacterial homeostasis.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with NTRK family mutations.

Background: The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure.

Methods: The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort.

Stress-activated brain-gut circuits disrupt intestinal barrier integrity and social behaviour.

Chronic stress underlies the etiology of both major depressive disorder (MDD) and irritable bowel syndrome (IBS), two highly prevalent and debilitating conditions with high rates of co-morbidity. However, it is not fully understood how the brain and gut bi-directionally communicate during stress to impact intestinal homeostasis and stress-relevant behaviours. Using the chronic social defeat stress (CSDS) model, we find that stressed mice display greater intestinal permeability and circulating levels of the endotoxin lipopolysaccharide (LPS) compared to unstressed control (CON) mice.

D1 and D2 neurons in the nucleus accumbens enable positive and negative control over sugar intake in mice.

Although the consumption of carbohydrates is needed for survival, their potent reinforcing properties drive obesity worldwide. In turn, sugar overconsumption reveals a major role for brain reward systems in regulating sugar intake. However, it remains elusive how different cell types within the reward circuitries control the initiation and termination of sugary meals.

Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint inhibitors.

Background: Although immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.

Methods: The profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed.

An inter-organ neural circuit for appetite suppression.

Glucagon-like peptide-1 (GLP-1) is a signal peptide released from enteroendocrine cells of the lower intestine. GLP-1 exerts anorectic and antimotility actions that protect the body against nutrient malabsorption. However, little is known about how intestinal GLP-1 affects distant organs despite rapid enzymatic inactivation.

as a Predictive Biomarker for Immune Checkpoint Inhibitors in Patients With Lung Adenocarcinoma.

The application of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer has significantly improved patient survival. However, most patients fail to respond to ICIs or develop drug resistance during treatment. Therefore, novel biomarkers are needed to predict the efficacy of ICIs or provide clues on how to overcome drug resistance.

Functional mechanism of hsa-miR-128-3p in epithelial-mesenchymal transition of pancreatic cancer cells via ZEB1 regulation.

Pancreatic cancer (PC) often correlates with high mortality due to late diagnosis, rapid metastasis, and resistance to chemotherapy. miR-128-3p has been validated as a tumor suppressor in PC. This study explored the functional mechanism of miR-128-3p in epithelial-mesenchymal transition (EMT) of PC cells.

Targeted paclitaxel-octreotide conjugates inhibited the growth of paclitaxel-resistant human non-small cell lung cancer A549 cells in vitro.

The application of chemotherapy in non-small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi-drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs-mediated targeted therapy against NSCLC.

Dissection and surgical approaches to the mouse jugular-nodose ganglia.

The jugular-nodose ganglia contain the sensory peripheral neurons of the vagus nerve, linking visceral organs to the medulla oblongata. Accessing these ganglia in smaller animals without damaging the vascular and neural structures may be challenging, as ganglionic fibers imbed deeply into the carotid sheath, and vagal parasympathetic fibers cross through the interior of the ganglia. We describe a practical protocol for locating and accessing the mouse jugular-nodose ganglia , including instructions for intraganglionic injections and postperfusion dissection.

Nausea and the Brain: The Chemoreceptor Trigger Zone Enters the Molecular Age.

Area postrema in brainstem has long been known to trigger emesis by detecting blood-borne toxins and pathogens. In this issue, Zhang and colleagues provide a single-cell molecular atlas of this region, opening new possibilities for harnessing its neurons in vivo.

Author Correction: Microbiota modulate sympathetic neurons via a gut-brain circuit.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Microbiota modulate sympathetic neurons via a gut-brain circuit.

Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content, regulating both physiological intestinal functions such as nutrient absorption and motility, and brain-wired feeding behaviour. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology. Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations.

Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood.

On the roles of the Duodenum and the Vagus nerve in learned nutrient preferences.

Background And Aim: In most species, including humans, food preference is primarily controlled by nutrient value. However, the gut-brain pathways involved in preference learning remain elusive. The aim of the present study, performed in C57BL6/J mice, was to characterize the roles in nutrient preference of two critical elements of gut-brain pathways, i.

Sugar Metabolism Regulates Flavor Preferences and Portal Glucose Sensing.

In most species, including humans, food preference is primarily controlled by nutrient value. In particular, glucose-containing sugars exert exquisitely strong effects on food choice via gut-generated signals. However, the identity of the visceral signals underlying glucose's rewarding effects remains uncertain.

A Neural Circuit for Gut-Induced Reward.

The gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that optical activation of gut-innervating vagal sensory neurons recapitulates the hallmark effects of stimulating brain reward neurons.

Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala.

Superior predatory skills led to the evolutionary triumph of jawed vertebrates. However, the mechanisms by which the vertebrate brain controls predation remain largely unknown. Here, we reveal a critical role for the central nucleus of the amygdala in predatory hunting.

Separate circuitries encode the hedonic and nutritional values of sugar.

Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar.

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite.

Reductions in calorie intake contribute significantly to the positive outcome of bariatric surgeries. However, the physiological mechanisms linking the rerouting of the gastrointestinal tract to reductions in sugar cravings remain uncertain. We show that a duodenal-jejunal bypass (DJB) intervention inhibits maladaptive sweet appetite by acting on dopamine-responsive striatal circuitries.

A genome-wide study of DNA methylation modified by epigallocatechin-3-gallate in the CAL-27 cell line.

In order to gain greater understanding of the mechanisms underlying the effect of epigallocatechin-3-gallate (EGCG) on DNA methylation and its chemopreventative action in oral squamous cell carcinoma (OSCC), a genome‑wide methylation and mRNA expression screen was performed in the CAL‑27 cell line with and without EGCG (100 µM) treatment. A total of 761 differentially methylated gene loci were identified following treatment with EGCG. Comparison of gene expression profiling in OSCC samples revealed 184 transcripts with a significant difference (P<0.

The effects of bisphosphonate on the remodeling of different irregular bones in mice.

Background: We aimed to compare the effects of bisphosphonate on the remodeling of irregular bones (the jaw and ilium) in mice after trauma.

Methods: To verify the feasibility of modeling osteonecrosis, 20 mice were injected intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group), dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR) group]. Mice then underwent extraction of the right maxillary first molar and creation of an artificial bony cavity in the ilium.