Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Influenza a virus NS1 resembles a TRAF3-interacting motif to target the RNA sensing-TRAF3-type I IFN axis and impair antiviral innate immunity.

BACKGROUND: Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection. Yet, it remains unclear if IAV NS1 can exploit a common mechanism to counteract these RNA sensing pathways to type I IFN production at once, then promoting viral propagation in the host. METHODS: Luciferase reporter assays were conducted to determine the effect of NS1 and its mutants on the RIG-I and TLR3 pathways to the activation of the IFN-ß and NF-κB promoters. Coimmunoprecipitation and confocal microscopic analyses were used to the interaction and colocalization between NS1 and TRAF3. Ubiquitination assays were performed to study the effect of NS1 and its mutants on TRAF3 ubiquitination. A recombinant mutant virus carrying NS1 E152A/E153A mutations was generated by reverse genetics for biochemical, ex vivo, and in vivo analyses to explore the importance of NS1 E152/E153 residues in targeting the RNA sensing-TRAF3-type I IFN axis and IAV pathogenicity. RESULTS: Here we report that NS1 subverts the RIG-I, TLR3, and TLR7 pathways to type I IFN production through targeting TRAF3 E3 ubiquitin ligase. NS1 harbors a conserved FTEE motif (a.a. 150-153), in which the E152/E153 residues are critical for binding TRAF3 to block TRAF3 ubiquitination and type I IFN production by these RNA sensing pathways. A recombinant mutant virus carrying NS1 E152A/E153A mutations induces higher type I IFN production ex vivo and in vivo, and exhibits the attenuated phenotype in infected mice, indicating the importance of E152/E153 residues in IAV pathogenicity. CONCLUSIONS: Together our work uncovers a novel mechanism of IAV NS1-mediated immune evasion to promote viral infection through targeting the RNA sensing-TRAF3-type I IFN axis.

Patients with preoperative asymptomatic pyuria are not prone to develop febrile urinary tract infection after ureteroscopic lithotripsy.

BACKGROUND: This study aimed to evaluate the association of asymptomatic pyuria before ureterorenoscopic lithotripsy (URSL) with postoperative febrile urinary tract infection (UTI). METHODS: This observational case-control study identified the patients undergoing URSL for ureteral stones between May 2011 and October 2015. The included patients were classified into two groups: the asymptomatic pyuria group (6-50 white blood cells [WBCs]/high-power field [HPF]) and the non-pyuria group (≤ 5 WBCs/HPF). All data were collected by reviewing medical records. Postoperative outcomes were collected in terms of febrile UTI, emergency visits, and stone-free rate. RESULTS: A total of 232 patients were included, 101 in the pyuria group, 131 in the non-pyuria group. Two (0.9%) patients developed febrile UTI after URSL and 12 (5.2%) patients visited emergency department for URSL-related symptoms. The overall stone-free rate was 90.9%. There was no significant difference between the pyuria and non-pyuria groups regarding febrile UTI, emergency visits, and stone-free rate. Multivariate analysis revealed that pyuria was neither significantly associated with postoperative febrile UTI (OR = 1.03, 95% CI = 0.06-18.10, P = 0.98), nor with emergency visits (OR = 0.48, 95% CI = 0.13-1.85, P = 0.29). CONCLUSIONS: Compared to the patients with sterile urine prior to URSL, those with asymptomatic pyuria were not prone to develop febrile UTI after URSL.

Preventing forgotten double J ureteral stents in a high-volume service medical center: An autoregistration monitoring system.

BACKGROUND: To evaluate the efficacy of an autoregistration monitoring system (ARMS) for tracking the placement and removal of ureteral stents. METHODS: The system was designed to tie in closely with the billing system. Once a stent was used and charged, a stent "episode" was created in the ARMS. When the stent was removed and the charge for the procedure was issued, the stent episode for that stent was removed automatically. The ARMS identified stents which exceeded their deadline, generating an alarm until the stent was removed and the ARMS updated. RESULTS: A total of 10 105 patients with 12 440 stent episodes were registered in the ARMS between March 2010 and August 2018. Of the 10 105 patients, 8597 (85.07%) were automatically detected to have had their stents removed before their deadline. We contacted the 1508 (14.93%) patients whose stents were not registered as having been removed by their deadline, of whom 122 (1.21%) had undergone stent removal at other hospitals, 490 (4.85%) had died, and 875 (8.66%) knew that they had ureteral stents inserted and were urged to come back for stent removal. Twenty-one patients (0.21%) did not know that they had implanted stents. None of these 21 patients were urological patients, and they had stents placed during urological consultation in an operating room. CONCLUSION: Our study showed that the ARMS reduced the manpower in tracking stent removal by 85.07% and that it was useful for detecting and preventing forgotten stents.

Role of urodynamics in management of urethral diverticulum in females.

BACKGROUND: Few studies have focused on the urodynamic findings of urethral diverticula (UD). We characterized the symptoms and urodynamic findings in women with UD. METHODS: A retrospective review of all women in a single center having surgical treatment for symptomatic UD between May 2004 and September 2014 was done. Lower urinary tract symptoms were evaluated with International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires. All patients underwent magnetic resonance imaging and videourodynamic study (VUDS) prior to surgery, and postoperative evaluation with VUDS. RESULTS: A total of 20 female patients were enrolled into the study. 12 (60%) UD patients presented with symptoms of stress urinary incontinence (SUI). However, there were merely 3 (15%) patients diagnosed as urodynamic SUI. 15 (75%) patients exhibited low catheter-free uroflow. Detrusor overactivity was demonstrated in 4 (20%) patients. Bladder outlet obstruction (BOO) was diagnosed in 8 (40%) cases. Postoperative VUDS revealed persistent BOO in 50% of patients with preoperative BOO. Of these, residual diverticulum was noted by VUDS in one patient. CONCLUSION: For UD patients with urinary incontinence or voiding dysfunction, VUDS is helpful in accurately characterizing these symptoms.