Background & Aims: Radiation-induced enteritis develops in cancer patients treated with radiotherapy in the abdominal and pelvic cavity, a condition that impairs their quality of life. Radiation injury depletes pr...
详细信息
Background & Aims: Radiation-induced enteritis develops in cancer patients treated with radiotherapy in the abdominal and pelvic cavity, a condition that impairs their quality of life. Radiation injury depletes proliferative intestinal stem cells;in response to this, the epithelium activates a regenerative program that facilitates the healing of the intestine. However, the mechanisms that induce the activation of the intestinal regenerative program are poorly characterized. Methods: In this study, we induced radiation-induced enteritis in mice through abdominal irradiation, mimicking clinical scenarios. Through imaging and flow cytometric analysis, we investigated the recruitment of macrophages to the small intestine during injury and healing. Additionally, we developed a coculture system for mouse and human intestinal organoids and macrophages to explore the cross talk between these cells. Then by combining in vivo ablation of macrophages, fluorescent lineage tracing, imaging, bulk RNA-sequencing (RNA-seq), single-cell RNA-seq, human intestinal organoids, and cell trajectory analysis, we studied the macrophage induction of intestinal regeneration at the cellular and molecular level. Results: Our findings revealed that macrophages are recruited around the intestinal stem cell compartment upon radiation injury, promoting a fetal-like reprogramming and proliferation of epithelial cells that drives the regeneration process. In contrast, macrophage ablation led to compromised regeneration. Moreover, our single-cell RNA-seq analysis identified key secreted molecules, neuregulin 1 and osteopontin, as pivotal players in regulating this process. Additionally, characterization of human macrophage/organoid cocultures and cell trajectory inference confirmed the conservation of macrophages' role in triggering the regenerative program in primary human cells. Conclusions: This study identifies macrophages as essential contributors to intestinal regeneration beyond their innate im
Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the retinal signal is unclear. To quantify this, we developed a Bay...
The emergence of and transitions between distinct phenotypes in isogenic cells can be attributed to the intricate interplay of epigenetic marks, external signals, and gene regulatory elements. These elements include c...
详细信息
Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. Th...
详细信息
Objective: To investigate whether Ershen Pill(ESP,二神丸) could alleviate the symptom of Pi(Spleen)-Shen(Kidney) yang deficiency(PSYD)-induced diarrhea in rat model and explore its anti-diarrhea mechanism. Methods: Se...
详细信息
Objective: To investigate whether Ershen Pill(ESP,二神丸) could alleviate the symptom of Pi(Spleen)-Shen(Kidney) yang deficiency(PSYD)-induced diarrhea in rat model and explore its anti-diarrhea mechanism. Methods: Seventy-five Sprague-Dawley rats were divided into 5 groups by a random number table, including control, positive, model, low-dose(LD) and high-dose(HD) ESP groups, 15 rats in each group. All the rats, except those in the control group, were developed PSYD induced-diarrhea based on its pathology and etiology. The rats in positive, LD and HD ESP groups were treated with Shenling Baizhu Pill(参苓白术丸), LD(1.05 g/kg) or HD(3.50 g/kg) ESP petroleum ether extract once a day for 2 weeks, respectively. Body weight change and diarrhea index were measured. The histology scores of the kidney were evaluated via hematoxylin and eosin(HE) staining. Aquaporin-3(AQP3) expression in the colon was analyzed by immunofluorescence, quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and Western blot, respectively. Results: Compared with the model group, oral administration of LD and HD ESP prevented body weight loss and inhibited diarrhea after 2-week treatment(P<0.05). Kidney deterioration was impeded, and the histology score in LD and HD ESP groups were 8.2 and 10.5, respectively, which were both higher than those in the model group(P<0.05). In addition, ESP treatment alleviated rat colitis, and HD ESP significantly improved the AQP3 positive staining intensity in the colon tissue compared with the model group. The result from Western blot revealed that AQP3 protein synthesis in colon tissue of LD and HD ESP groups increased by 2.1-and 5.9-fold compared with the model group(P<0.05). qR T-PCR result showed that AQP3 gene expression in the HD ESP group was also up-regulated by 2.5-fold normalized to the model group(P<0.05). Conclusion: ESP extract effectively alleviates the symptoms of PSYD and relieves PSYD-induced diarrhea by improving AQP3 synthesis in the col
作者：
Mike WiningerReva JohnsonPhD
has faculty appointments at the University of Hartford (Prosthetics Program) and Yale University (Department of Biostatistics) and is a statistician of clinical trials with the Department of Veterans Affairs. PhD
is a professor in the Department of Mechanical Engineering and Bioengineering at Valparaiso University.
How Bayesian inference can decode movement intentions and control the next generation of powered prostheses. By Mike Wininger and Reva Johnson
How Bayesian inference can decode movement intentions and control the next generation of powered prostheses. By Mike Wininger and Reva Johnson
Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. During metastasis, a developmental program known as the epithelial-mesenchymal transition (EMT) plays a critical role....
详细信息
Graphical causal models are an important tool for knowledge discovery because they can represent both the causal relations between variables and the multivariate probability distributions over the data. Once learned, ...
详细信息
暂无评论