NLRP3 Inflammasome: An Emerging Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is currently the most prevalent neurological disease, and no effective and practical treatments and therapies exist. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3) inflammasome is vital in the human innate immune response. However, when the NLRP3 inflammasome is overactivated by persistent stimulation, several immune-related diseases, including AD, atherosclerosis, and obesity, result. This review will focus on the composition and activation mechanism of the NLRP3 inflammasome, the relevant mechanisms of involvement in the inflammatory response to AD, and AD treatment targeting NLRP3 inflammasome. This review aims to reveal the pathophysiological mechanism of AD from a new perspective and provide the possibility of more effective and novel strategies for preventing and treating AD.

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms.

Background: Exophytic papillary urothelial neoplasms (EPUN) are difficult to diagnose pathologically and are well-known for their heterogeneous prognoses. Thus, searching for an objective and accurate diagnostic marker is of great clinical value in improving the outcomes of EPUN patients. PHH3 was reported to be expressed explicitly in the mitotic phase of the cell cycle, and recent studies have shown that PHH3 expression was associated with the differential diagnosis and prognosis of many tumors. However, its significance in EPUN remains unclear. This study aimed to determine the expression of PHH3 in different EPUN, compare its expression with cell-cycle related proteins Ki67 and P53, and analyze its significance in the differential diagnosis and prognostic value for high-grade papillary urothelial carcinoma (HGPUC), low-grade papillary urothelial carcinoma (LGPUC), papillary urothelial neoplasm of low malignant potential (PUNLMP) and urothelial papilloma (UP). Methods: We retrospectively analyzed the pathological diagnosis and clinical features of 26 HGPUC cases, 43 LGPUC cases, 21 PUNLMP cases and 11 UP cases. PHH3, Ki67 and P53 were detected by immunohistochemistry in 101 EPUN cases samples. The cut-off values of PHH3 mitosis count (PHMC), HE mitosis count (HEMC), Ki67 and P53 in the different EPUN were determined using the ROC curve. The distribution of counts in each group and its relationship with clinical parameters and prognosis of EPUN patients were also analyzed. Results: The determination coefficient (R2 = 0.9980) of PHMC were more potent than those of HEMC (R2 = 0.9734) in the EPUN mitotic counts microscopically by both pathologists. Of the 101 EPUN cases investigated, significant positive linear correlations were found between PHMC and HEMC, PHMC and Ki67, and HEMC and Ki67 (P < 0.0001). In HGPUC, LGPUC, PUNLMP and UP, a decreasing trend was observed in the median and range of PHMC/10HPFs, HEMC/10HPFs, Ki67 (%) and P53 (%). PHMC, HEMC, Ki67 and P53 were associated with different clinical parameters of EPUN. PHMC, HEMC, Ki67 and P53 were found to exhibit substantial diagnostic values among different EPUN and tumor recurrence. Based on the ROC curve, when PHMC was >48.5/10HPFs, a diagnosis of HGPUC was more likely, and when PHMC was >13.5/10HPFs, LGPUC was more likely. In addition, when PHMC was >5.5/10HPFs, the possibility of non-infiltrating LGPUC was greater. Kaplan-Meier survival curve analysis showed that the median recurrence-free survival (RFS) for cases with PHMC > 13.5/10HPFs and HEMC > 14.5/10HPFs were 52.5 and 48 months, respectively, and their respective hazard ratio was significantly higher (Log-rank P < 0.05). Conclusion: PHH3 exhibited high specificity and sensitivity in diagnosing EPUN. Combined with HEMC, Ki67 and P53, it can assist in the differential diagnosis of EPUN and estimate its clinical progression with high predictive value to a certain extent.

The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors.

BACKGROUND: Leucine-rich alpha-2-glycoprotein-1 (LRG1) is widely involved in proliferation, migration, and invasion of various tumor cells. Recent studies have evaluated the potential of LRG1 as both an early tumor and a prognostic biomarker. METHOD: The relevant literature from PubMed is reviewed in this article. RESULTS: It has been found that LRG1 mainly acts on the regulatory mechanisms of angiogenesis, epithelial-mesenchymal transition (EMT), and apoptosis by transforming growth factor (TGF-ß) signaling pathway as well as affecting the occurrence and development of the tumors. Moreover, with advancement of research, LRG1 regulation pathways which are independent of TGF-ß signaling pathway have been gradually revealed in different tumor cells; There are several studies on the biological effects of LRG1 as an inflammatory factor, vascular growth regulator, cell adhesion, and a cell viability influencing factor. In addition, various tumor suppression methods which are based on regulation of LRG1 levels have also shown high potential clinical value. CONCLUSIONS: LRG1 are critical for the processes of tumorigenesis, development, and metastasis in various tumors. The present study reviewed the latest research on the achievements of LRG1 in tumor genesis and development. Further, this study also discussed the related molecular mechanisms of various biological functions of LRG1.