High mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. The expression of HMGB1 has been described in many types of cancers, but the role of HMGB1 in nasopharyngeal carcinoma (NPC) is unknown. The aim of this study was to analyse the roles of HMGB1 in NPC progression and clinical outcome using NPC clinical samples. In an immunohistochemical study, HMGB1 had high expression in 89 of 166 cases of NPC (53.6%). HMGB1 overexpression was significantly associated with T classification (p = 0.01), N classification (p = 0.003), distant metastasis (p = 0.046), and clinical stage (p < 0.001). Patients with higher levels of HMGB1 expression had poorer overall survival and disease-free survival, whereas patients with lower levels of HMGB1 expression had better survival. Multivariate analysis showed that HMGB1 expression was an independent prognostic indicator for patient survival. Disruption of endogenous HMGB1 using small interfering RNAs suppressed NPC cell invasive ability. These data support the notion that HMGB1 overexpression has a role in the progression of NPC and hence its poor clinical outcome.
Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and function. Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis. However, the underlying cellular events in podocyte controlled by Cdc42 remain unclear. Here, we assessed the cellular mechanisms by which Cdc42 regulates podocyte apoptosis. We found that the expression of Cdc42 and its activity were significantly decreased in high glucose-, lipopolysaccharide- or adriamycin-injured podocytes. Reduced Cdc42 expression in vitro and in vivo by small interfering RNA and selective Cdc42 inhibitor ML-141, respectively, caused podocyte apoptosis and proteinuria. Our results further demonstrated that insufficient Cdc42 or Nwasp, its downstream effector, could decrease the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Moreover, our data indicated that the loss of stress fibers caused by Cdc42/Nwasp deficiency also decreased Yes-associated protein (YAP) mRNA and protein expression, and induced podocyte apoptosis. Podocyte apoptosis induced by Cdc42/Nwasp/stress fiber deficiency was significantly inhibited by overexpressing-active YAP. Thus, the Cdc42/Nwasp/stress fibers/YAP signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary Cdc42 would be one potent way to prevent proteinuria kidney diseases.
Appendicitis is a rare but life-threatening complication in patients undergoing haematopoietic stem cell transplantation (HSCT). Infectious complications arising from the gastrointestinal tract are common in immunocompromised patients with haematologic malignances. 1,2 Serious infection often occurs in neutropaenic patients, especially during HSCT. Acute appendicitis is frequently reported in leukaemia patients after chemotherapy but is rarely reported during HSCT. The Alvarado Scoring System (the MANTRELS acronym stands for 'Migration, Anorexia-acetone, Nausea-vomiting, Tenderness in right quadrant, Reboud pain, Elevation of temperature, Leukocytosis, Shif to the left'), which is shortened to ASS-MANTRELS, has been used to diagnose acute appendicitis. 3 However, acute appendicitis occurred in HSCT patients during the neutropaenic phase. The indexes of leukocytosis and shift to the left (LS) of the ASS-MANTRELS were not applicable to these patients. Therefore, a standard criterion applicable for such patients who underwent HSCT was set up. Here we report 10 cases of acute appendicitis, which were selected from 776 sequential HSCTs.
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