Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

Effect of broad-spectrum antibiotics on bacterial translocation in burned or septic rats.

BACKGROUND: Antibiotics are frequently used to treat critically ill patients, and its use is often accompanied by intestinal dysbiosis that might further lead to bacterial translocation (BT). Nevertheless, studies on the relationship between antibiotic therapy and BT are rare. In the present study, we investigated the effect of broad-spectrum antibiotics on BT in an experimental rat model of burn or sepsis injury. METHODS: The septic rat model was simulated by a second insult with lipopolysaccharides after burn injury. Ninety-two male Sprague-Dawley rats were randomly divided into control, burn, and sepsis groups (n = 8 or 9, each group), and the latter two groups were then treated with imipenem or ceftriaxone for 3 or 9 days. The mesenteric lymph nodes, liver, lungs, and blood were collected at each time point under sterile conditions for quantitative bacterial culture and strain identification. The differences between the groups were compared by Fisher exact test or Mann-Whitney U test. RESULTS: Only minimal Escherichia coli translocation to the mesenteric lymph nodes was observed in the normal control group, in which the BT rate was 12.5%. Burn injury did not affect the BT rate (Burn group vs. Control group, 12.5% vs. 12.5%, P = 1.000), whereas the BT rate showed an increased trend after the second insult with lipopolysaccharide (Sepsis group vs. Control group, 44.4% vs. 12.5%, P = 0.294), and many strains of Enterobacteria spp. were detected in distant organs (liver, lung, and blood) [Sepsis group vs. Control group, 0 (0,3) vs. 0 (0,0), U = 20, P = 0.045]. After the antibiotic treatment, BT to the distant organs was increased in burned rats [Burn IT3 group vs. Burn group, 0 (0,2) vs. 0 (0,0); Burn IT9 group vs. Burn group, 0 (0,1) vs. 0 (0,0); Burn CT9 group vs. Burn group, 0 (0,2) vs. 0 (0,0); all U = 20 and P = 0.076] but decreased in septic rats [Sepsis CT3 group vs. Sepsis group, 0 (0,0) vs. 0 (0,3), U = 20, P = 0.045]. The total amount of translocated bacteria, regardless of which antibiotic was used, was increased in burned rats [Burn IT9 group vs. Burn group, 2.389 (0,2.845) vs. 0 (0,2.301) Log10 colony-forming units (CFU)/g, U = 14, P = 0.034; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,2.301) Log10 CFU/g, U = 10.5, P = 0.009], but there was a slightly decreased trend in septic rats [Sepsis IT9 group vs. Sepsis group, 2.301 (2,3.146) vs. 0 (0,4.185) Log10 CFU/g, U = 36, P = 0.721; Sepsis CT9 group vs. Sepsis group, 2 (0,3.279) vs. 0 (0,4.185) Log10 CFU/g, U = 32.5, P = 0.760]. Remarkably, the quantity of Enterococci spp. dramatically increased after broad-spectrum antibiotic treatment in both the burned and septic groups [Burn IT3 group vs. Burn group, 1 (0,5.164) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn IT9 group vs. Burn group, 1 (0,2.845) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,0) Log10 CFU/g, U = 8; Burn CT9 group vs. Burn group, 1 (0,4.326) vs. 0 (0,0) Log10 CFU/g, U = 16; Sepsis IT3 group vs. Sepsis group, 2.477 (0,2.903) vs. 0 (0,0) Log10 CFU/g, U = 4.5; Sepsis IT9 group vs. Sepsis group, 2 (0,3.146) vs. 0 (0,0) Log10 CFU/g, U = 9; Sepsis CT3 group vs. Sepsis group, 1.151 (0,2.477) vs. 0 (0,0) Log10 CFU/g, U = 18; Sepsis CT9 group vs. Sepsis group, 2 (0,3) vs. 0 (0,0) Log10 CFU/g, U = 13.5; all P < 0.05]. CONCLUSIONS: Broad-spectrum antibiotics promote BT in burned rats but prevent BT in septic rats, especially preventing BT to distant organs, such as the liver and lung. Moreover, Enterococci spp. with high drug resistance and high pathogenicity translocated most after antibiotic treatment.

Effects of rhubarb on the expression of glucocorticoids receptor and regulation of cellular immunity in burn-induced septic rats.

BACKGROUND: It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats. METHODS: Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18); each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4,CD8,CD4CD25T cells, CD19B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement. RESULTS: The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01; t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05; t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4 T cells, CD4/CD25 T cell ratio, and CD19 B cells in the peripheral blood were significantly increased in the sepsis group (t = -3.395, P < 0.01; t = 2.568, P < 0.05; t = 2.993, P < 0.05, vs. control mice, respectively). However, the percentage of NK cells in the peripheral blood were significantly decreased in the sepsis group (t = -2.022, P < 0.05, vs. control mice). Twelve hours after sepsis, the percentage of CD8 T cells were significantly decreased in the peripheral blood in the sepsis group (t = -2.191, P < 0.05, vs. control mice) and were significantly increased in the rhubarb group (t = 2.953, P < 0.05, vs. sepsis mice). Seventy-two hours after sepsis, the ratio of CD4/CD25 T cell in peripheral blood were significantly increased in the sepsis group (t = 2.508, P < 0.05, vs. control mice) while were significantly decreased in the rhubarb group (t = 3.378, P < 0.05, vs. control mice). Furthermore, the percentages of CD19 B cell in peripheral blood were significantly decreased at 72 h in the rhubarb group (t = 2.041, P < 0.05 vs. sepsis group). CONCLUSIONS: Rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis processes.

Lycopene mitigates ß-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer's disease rats.

The choroid plexus is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, whether lycopene is involved in inflammatory responses at the choroid plexus in the early stages of Alzheimer's disease, and its molecular underpinnings are elusive. In this rat study, lycopene was used to investigate its protective effects on inflammation caused by ß-amyloid. We characterized the learning and memory abilities, cytokine profiles of circulating TNF-α, IL-1ß and IL-6ß in the serum and the expressions of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein at the choroid plexus. The results showed that functional deficits of learning and memory in lycopene treatment groups were significantly improved compared to the control group without lycopene treatment in water maze test. The levels of serum TNF-α, IL-1ß and IL-6ß were significantly increased, and the expressions of TLR4 and NF-κB p65 mRNA and protein at the choroid plexus were up-regulated, indicating inflammation response was initiated following administration of Aß1-42. After intragastric pretreatment with lycopene, inflammatory cytokines were significantly reduced and lycopene also reversed the Aß1-42 induced up-regulation of TLR4 and NF-κB p65 mRNA and protein expressions at the choroid plexus. These results provided a novel evidence that lycopene significantly improved cognitive deficits and were accompanied by the attenuation of inflammatory injury via blocking the activation of NF-κB p65 and TLR4 expressions and production of cytokines, thereby endorsing its usefulness for diminishing ß-amyloid deposition in the hippocampus tissues.