Gut microbiota changes in patients with Alzheimer's disease spectrum based on 16S rRNA sequencing: a systematic review and meta-analysis.

Background: The gut microbiota (GM) is hypothesized to play roles in Alzheimer's disease (AD) pathogenesis. In recent years, many GM composition and abundance investigations in AD patients have been conducted; however, despite this work, some results remain controversial. Therefore, we conducted a systematic review and meta-analysis using 16S ribosomal RNA (16S rRNA) sequencing to explore GM alterations between patients with AD spectrum and healthy controls (HCs). Methods: A systematic and comprehensive literature search of PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc database, WanFang database and Social Sciences Citation Index databases was conducted from inception to January 2023. Inclusion and exclusion criteria were strictly defined, and two researchers independently screened and extracted information from selected studies. Data quality were evaluated according to the "Cochrane system evaluator manual" and pooled data were comprehensively analyzed using Stata 14 software with standardized mean differences (SMDs) and 95% confidence intervals (95% CIs) used to measure effect sizes. Also, geographical heterogeneity effects (related to cohorts) on GM abundance were examined based on subgroup meta-analyses if sufficient studies reported outcomes. Finally, publication bias was assessed using funnel plots. Results: Out of 1566 articles, 13 studies involving 581 patients with AD spectrum and 445 HCs were deemed eligible and included in our analysis. In summary, a decreased microbiota alpha diversity and a significantly distinct pattern of clustering with regard to beta diversity were observed in AD spectrum patients when compared with HCs. Comparative analyses revealed a decreased Ruminococcus, Faecalibacterium, Lachnospira, Dialister, Lachnoclostridium, and Roseburia abundance in AD spectrum patients while Phascolarctobacterium, Lactobacillus, and Akkermansia muciniphila were more enriched in patients when compared to HCs. Furthermore, regional variations may have been in play for intestinal microbes such as Bacteroides, Bifidobacterium, and Alistipes. Conclusion: Our meta-analysis identified alterations in GM abundance in patients with AD spectrum, with 12 genera from four major phyla significantly associated with AD. Moreover, we provided evidence for region-specific alterations in Bacteroides, Bifidobacterium, and Alistipes abundance. These findings may have profound implications for the development of innovative GM-based strategies to prevent and treat AD. Systematic review registration: https://doi.org/10.37766/inplasy2024.6.0067, identifier INPLASY202460067.

The immune landscape in apical periodontitis: From mechanism to therapy.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

Interplay of RUNX2 and KLF4 in initial commitment of odontoblast differentiation.

Odontoblast differentiation is a key process in dentin formation. Mouse dental papilla cells (mDPCs) are pivotal in dentinogenesis through their differentiation into odontoblasts. Odontoblast differentiation is intricately controlled by transcription factors (TFs) in a spatiotemporal manner. Previous research explored the role of RUNX2 and KLF4 in odontoblast lineage commitment, respectively. Building on bioinformatics analysis of our previous ATAC-seq profiling, we hypothesized that KLF4 potentially collaborates with RUNX2 to exert its biological role. To investigate the synergistic effect of multiple TFs in odontoblastic differentiation, we first examined the spatiotemporal expression patterns of RUNX2 and KLF4 in dental papilla at the bell stage using immunostaining techniques. Notably, RUNX2 and KLF4 demonstrated colocalization in preodontoblast. Further, immunoprecipitation and proximity ligation assays verified the interaction between RUNX2 and KLF4 in vitro. Specifically, the C-terminus of RUNX2 was identified as the interacting domain with KLF4. Functional implications of this interaction were investigated using small hairpin RNA-mediated knockdown of Runx2, Klf4, or both. Western blot analysis revealed a marked decrease in DSPP expression, an odontoblast differentiation marker, particularly in the double knockdown condition. Additionally, alizarin red S staining indicated significantly reduced mineralized nodule formation in this group. Collectively, our findings highlight the synergistic interaction between RUNX2 and KLF4 in promoting odontoblast differentiation from mDPCs. This study contributes to a more comprehensive understanding of the regulatory network of TFs governing odontoblast differentiation.

A magnetic beads-based ligand fishing method Coupled with UHPLC-QTOF MS for screening and identification of α-glucosidase inhibitors from Houttuynia cordata Thunb.

In this study, a method for the screening and identification of α-glucosidase inhibitors from natural products was developed. The α-glucosidase was immobilized on carboxyl terminated magnetic beads to form a ligand fishing system to screen the potential inhibitors. A total of 9 compounds were fishing out from the crude Houttuynia cordata Thunb. extract. Meanwhile, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) was used for the identification of the chemical structures, including 3 chlorogenic acid isomers, 2 flavone C-glycosides and 4 flavone O-glycosides. The combination of enzyme immobilization magnetic beads and UHPLC-QTOF MS could be used for the screening of bioactive multi-components from herbs with appropriate targets. Taking the advantage of the specificity of enzyme binding and the convenience of magnetic separation, the method has great potential for rapid screening of α-glucosidase inhibitors from complicated natural product extracts.