The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtbinfected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.
Population-based epidemiologic studies can provide important insight regarding the role of the microbiome in human health and disease. Buccal cells samples using commercial mouthwash have been obtained in large prospective cohorts for the purpose of studying human genomic DNA. We aimed to better understand if these mouthwash samples are also a valid resource for the study of the oral microbiome. We collected one saliva sample and one Scope mouthwash sample from 10 healthy subjects. Bacterial 16S rRNA genes from both types of samples were amplified, sequenced, and assigned to bacterial taxa. We comprehensively compared these paired samples for bacterial community composition and individual taxonomic abundance. We found that mouthwash samples yielded similar amount of bacterial DNA as saliva samples (p from Student’s t-test for paired samples = 0.92). Additionally, the paired samples had similar within sample diversity (p from = 0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for diversity when analyzed by unsupervised hierarchical cluster analysis. No significant difference was found in the paired samples with respect to the taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q = 0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19), and Porphyromonas (q = 0.60). These results show that mouthwash samples perform similarly to saliva samples for analysis of the oral microbiome. Mouthwash samples collected originally for analysis of human DNA are also a resource suitable for human microbiome research.
Background: The Asian American, Native Hawaiian, and Pacific Islander (AANHPI) aging population is rapidly growing and the burden of Alzheimer’s disease and its related dementias (ADRD) will likely mirror this demographic growth. AANHPIs face significant barriers in obtaining timely ADRD diagnosis and services; yet little is known about ADRD in this population. Objective: The study objective is to conduct a systematic review on the published literature on ADRD among AANHPIs to identify gaps and priorities to inform future research and action plans. Methods: The systematic review was conducted following the PRISMA Protocol for Systematic Reviews. Co-author (TR), an experienced Medical Librarian, searched PubMed, EMBASE, PsycINFO, Cochrane Central of Clinical Trials, Ageline, and Web of Science for peer-reviewed articles describing ADRD among AANHPIs. The search was not limited by language or publication date. Each citation was reviewed by two trained independent reviewers. Conflicts were resolved through consensus. Results: The title/abstract and full texts of 1,447 unique articles were screened for inclusion, yielding 168 articles for analysis. Major research topics included prevalence, risk factors, comorbidities, interventions and outreach, knowledge and attitudes, caregiving, and detection tools. A limited number of studies reported on national data, on NHPI communities generally, and on efficacy of interventions targeting AANHPI communities. Conclusion: To our knowledge, this is the first systematic review on ADRD among AANHPI populations. Our review provides a first step in mapping the extant literature on ADRD among this underserved and under-researched population and will serve as a guide for future research, policy, and intervention.
With growing numbers of aging Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs), the availability of culturally and linguistically appropriate screening tools for Alzheimer’s disease and its related dementias (ADRD) is needed. The aim of this scoping review is to summarize the tools that have been adapted for and validated among the AANHPI population. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for systematic reviews, six databases were searched for peer-reviewed articles describing ADRD among AANHPIs. Among 1,477 articles screened for inclusion, 15 articles were included in the final analysis. Results showed a paucity of studies that psychometrically validate tools among this population. Furthermore, studies that culturally adapted and/or translated existing tools mostly targeted East Asian American populations. Our review provides a first step in mapping the extant literature on ADRD screening tools for this underresearched population and will serve as a guide for future research, policy, and intervention.
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