Dl-3-N-butylphthalide alleviates renal ischemia-reperfusion injury by down-regulating NF-κB signaling pathway and inhibiting cell pyroptosis in rat models / 器官移植

Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.

Research progress of NF-κB signaling pathway in kidney ischemia-reperfusion injury / 器官移植

Kidney ischemia-reperfusion injury (IRI) is the major cause of poor prognosis after kidney transplantation and partial nephrectomy. Besides, it is also a critical pathophysiological process of acute kidney injury. Consequently, the prevention and treatment of kidney IRI are of significance to improve clinical prognosis of recipients undergoing kidney transplantation. However, the mechanism underlying IRI is complex, and the exact mechanism remains elusive. Inflammation, as one of the main pathogenesis of IRI, plays a significant role in IRI-induced kidney injury. Nuclear factor (NF)-κB, as a rapid response transcription factor, has been proven to be involved in the regulation of inflammation during kidney IRI. Therefore, in this article, the structure of NF-κB, the activation pattern of NF-κB signaling pathway, the regulatory mechanisms of NF-κB upstream and downstream signaling pathways in kidney IRI were reviewed, and the role of NF-κB signaling pathway in kidney IRI was investigated, aiming to provide novel clinical ideas for the prevention and treatment of kidney IRI.

Role of NLRP3 inflammasome and related inflammatory signaling pathways in renal ischemia-reperfusion injury / 器官移植

Renal ischemia-reperfusion injury (IRI) commonly occurs in renal transplantation, which is an important pathophysiological process that causes acute renal failure and severely affects clinical prognosis of the recipients. Inflammatory response plays a critical role in the pathogenesis and pathological process of IRI. Activated NOD-like receptor protein 3(NLRP3) inflammasome can mediate the maturation and release of various pro-inflammatory cytokines, thereby regulating the inflammatory response and relevant cell functions. In this article, the mechanism underlying NLRP3 inflammasome and its related inflammatory signaling pathway in renal IRI were reviewed, aiming to provide novel ideas for clinical prevention and treatment of renal IRI.

The progress on the mechanism of NLRP3 inflammasome in renal ischemia-reperfusion injury / 中华泌尿外科杂志

Renal ischemia-reperfusion injury often occurs during operations that need to block the blood supply of the kidneys. It is an important pathophysiological process that affects the recovery of kidney function and causes acute renal failure. Activated NLRP3 inflammasome can mediate the maturation and release of a variety of pro-inflammatory factors, and participate in the inflammatory response in renal ischemia-reperfusion injury, thereby regulating body inflammation and related cell functions. This article summarized how NLRP3 inflammasome mediated the occurrence of inflammation in renal ischemia reperfusion injury, and further provied a new basis for the prevention and treatment of renal ischemia-reperfusion injury.

Artesunate alleviates renal ischemia-reperfusion injury in rats by inhibiting pyroptosis via NLRP3 inflammasome / 器官移植

Objective To investigate the effect and mechanism of artesunate on renal ischemia-reperfusion injury (IRI) in rat. Methods Twenty-five SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), low-dose artesunate group (ART-L group), high-dose artesunate group (ART-H group) and NLRP3 inflammasome inhibitor group (INF39 group), with 5 rats in each group. The levels of serum creatinine (Scr), blood urea nitrogen (BUN) and pathological damage of renal tissue were analyzed. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum were quantitatively measured. The expression level of IL-1β in renal tissues was determined by immunohistochemical staining. The expression levels of pyroptosis-related proteins were detected by fluorescent staining and Western blot. Results Compared with the Sham group, the levels of Scr and BUN were higher, the renal tissue injury was aggravated, the expression levels of TNF-α, IL-6 and IL-1βwere higher, and the expression levels of kidney injury molecule (KIM-1), pyroptosis-related protein NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase-1), Gasdermin D (GSDMD) and IL-1β proteins were higher in the IRI group. Compared with the IRI group, the levels of Scr and BUN were decreased, the renal tissue injury was mitigated, the expression levels of TNF-α, IL-6 and IL-1β were down-regulated, and the expression levels of KIM-1, NLRP3, Caspase-1, GSDMD and IL-1β proteins were down-regulated in the ART-L, ART-H and INF39 groups. Conclusions Artesunate may inhibit pyroptosis induced by NLRP3 inflammasome, down-regulate the expression levels of pyroptosis -related proteins, reduce the release of inflammatory factors after renal IRI and alleviate renal IRI.

Progress of unilateral breast cancer undergoing contralateral prophylactic mastectomy / 国际外科学杂志

A growing number of people with unilateral breast cancer have chosen to undergo contralateral prophylactic mastectomy in order to prevent the occurrence of second primary breast cancer and thus avoid associated treatment and death. Contralateral prophylactic mastectomy has been considered beneficial in high-risk populations, such as premenopausal BRCA1/2 mutation carriers. As a result, contralateral prophylactic mastectomy acceptance in patients with no such mutation is controversial. Contralateral prophylactic mastectomy can reduce the risk by up to 95%. Therefore, it is very important to evaluate the risk of contralateral breast cancer and to make appropriate surgical treatment. A review of risk factors for contralateral breast cancer and the benefits of contralateral prophylactic mastectomy in patients with unilateral breast cancer is presented.

Research progress of CDK4/6 inhibitors in ER-positive and HER2-negative advanced breast cancer / 国际外科学杂志

Endocrine therapy is one of the standard treatment options for breast cancer which plays an important role in treating patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer.However,some patients develop resistance during therapy due to factors such as tumor heterogeneity,which is particularly acute in the treatment of advanced breast cancer.Based on aiming at a rational and effective treatment,some clinical trials recently have demonstrated that compared to endocrine therapy alone,cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy can significantly improve the prognosis of ER-positive,HER2-negative advanced breast cancer.Its main products are Palbociclib,Ribociclib and Abemaciclib.This review mainly focuses on the mechanism and related clinical trials of CDK4/6 inhibitor inhibitors in ER-positive,HER2-negative advanced breast cancer.