RESUMO
Recent investigations in neuroscience implicate the role of microbial-derived metabolites, such as short-chain fatty acids (SCFAs) in brain health and disease. The SCFAs acetate, propionate and butyrate have pleiotropic effects within the nervous system. They are crucial for the maturation of the brain's innate immune cells, the microglia, and modulate other glial cells through the aryl-hydrocarbon receptor. Investigations in preclinical and clinical models find that SCFAs exert neuroprotective and antidepressant affects, while also modulating the stress response and satiety. However, many investigations thus far have not assessed the impact of sex on SCFA activity. Our novel investigation tested the impact of physiologically relevant doses of SCFAs on male and female primary cortical astrocytes. We find that butyrate (0-25 âµM) correlates with increased Bdnf and Pgc1-α expression, implicating histone-deacetylase inhibitor pathways. Intriguingly, this effect is only seen in females. We also find that acetate (0-1500 âµM) correlates with increased Ahr and Gfap expression in males only, suggesting immune modulatory pathways. In males, propionate (0-35 âµM) correlates with increased Il-22 expression, further suggesting immunomodulatory actions. These findings show a novel sex-dependent impact of acetate and butyrate, but not propionate on astrocyte gene expression.
RESUMO
OBJECTIVE: A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. DESIGN: We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples ('ON' and 'OFF' the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. RESULTS: The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. CONCLUSIONS: CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.
Assuntos
Colo/microbiologia , Neoplasias do Colo/microbiologia , Pólipos do Colo/microbiologia , Microbioma Gastrointestinal , RNA Ribossômico 16S/análise , Neoplasias Retais/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/análise , Bacteroidetes/imunologia , Bacteroidetes/isolamento & purificação , Estudos de Casos e Controles , Quimiocina CCL20/genética , Quimiocina CXCL1/genética , Neoplasias do Colo/genética , Pólipos do Colo/genética , Fezes/microbiologia , Feminino , Firmicutes/imunologia , Firmicutes/isolamento & purificação , Microbioma Gastrointestinal/genética , Expressão Gênica , Humanos , Interleucina-17/genética , Interleucina-23/genética , Mucosa Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Prevotella/imunologia , Prevotella/isolamento & purificação , Estudos Prospectivos , Neoplasias Retais/genéticaRESUMO
The following article is the last in a series that focuses on unique and effective human resources recruiting and retention tactics in Michigan hospitals. The education of health care employees is key to having a qualified work force. And paying for the further education of current employees is an easy way to supply a hospital with the registered nurses they need.
Assuntos
Recursos Humanos de Enfermagem Hospitalar/educação , Recursos Humanos de Enfermagem Hospitalar/provisão & distribuição , Desenvolvimento de Pessoal , Humanos , Michigan , Lealdade ao TrabalhoRESUMO
For the third part in the series of articles featuring innovative human resources programs in Michigan hospitals, the focus is on training staff. Hayes Green Beach Memorial Hospital, Charlotte, has implemented a program that ensures a new employee's compliance with training requirements and reduces the headaches that can come with fitting training into an already full work schedule.
Assuntos
Hospitais Comunitários/organização & administração , Capacitação em Serviço/métodos , Administração de Recursos Humanos em Hospitais , Fidelidade a Diretrizes , Humanos , Michigan , Inovação Organizacional , Recursos HumanosRESUMO
For the second part in the series of articles featuring human resources initiatives in Michigan hospitals (part one appeared in the November/December issue of Michigan Health & Hospitals magazine), the spotlight is on Lakeland Regional Health System, with three hospitals in southwest Nichigan. It has changed its culture of care to be more oriented toward service.
