Erianin promotes apoptosis and inhibits Akt-mediated aerobic glycolysis of cancer cells.

Highly activated aerobic glycolysis provides the metabolic requirements for tumor cell growth and proliferation. Erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has been reported to exert antitumor activity in multiple cancers. However, whether Erianin exerts inhibitory effects on aerobic glycolysis and the inherent mechanism remain poorly defined in non-small cell lung cancer (NSCLC). Here, we showed that Erianin inhibited the cell viability and proliferation, and induced apoptosis in NSCLC cells. Moreover, Erianin overtly suppressed aerobic glycolysis via decreasing HK2 expression. Mechanistically, Erianin dose-dependently curbed the Akt-GSK3ß signaling pathway phosphorylation activation, which afterwards downregulated HK2 expression. Meanwhile, Erianin inhibited HCC827 tumor growth in vivo. Taken together, our results suggest that the natural product Erianin can suppress aerobic glycolysis and exert potent anticancer effects via the Akt-GSK3ß signaling pathway in NSCLC cells.

Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of Survivin.

Human malignancies exhibit elevated levels of survivin, and have been linked to poor prognosis. Targeting survivin expression is a promising therapeutic strategy against cancer cells. Natural compounds have become a hot topic in research due to their non-toxic, non-invasive, and efficient treatment of multiple diseases. In this current investigation, it was discovered that Dioscin, as a natural compound, exerted profound antitumor activity against NSCLC cell lines, inhibiting NSCLC cell viability and promoting apoptosis. Further mechanistic studies showed that Dioscin promoted ubiquitination-mediated survivin degradation via strengthening the interaction between survivin and the E3 ubiquitin ligase Fbxl7. Furthermore, Dioscin exhibited a strong tumor suppressive effect in xenograft tumor models, and Dioscin treatment led to a notable decrease in tumor volume and weight. Based on our findings, Dioscin is expected to be a potential antitumor agent for non-small cell lung cancer treatment.

Gastrodin destabilizes survivin and overcomes pemetrexed resistance.

Survivin is a bifunctional protein that plays crucial roles in tumorigenesis. In the present study, we discovered that the natural product gastrodin suppressed the cell viability and colony formation of non-small cell lung cancer (NSCLC) cell lines A549, HCC827, and H460 in a dose-dependent manner. In addition, gastrodin enhanced the protein levels of cleaved-caspase 3 by activating the endogenous mitochondrial apoptosis pathway. Gastrodin inhibits protein kinase B (Akt)/WEE1/cyclin-dependent kinase 1 (CDK1) signaling to downregulate survivin Thr34 phosphorylation. Survivin Thr34 dephosphorylation caused by gastrodin interfered with the binding of ubiquitin-specific protease 19 (USP19), which eventually destabilized survivin. We revealed that the growth of NSCLC xenograft tumors was markedly suppressed by gastrodin in vivo. Furthermore, gastrodin overcomes pemetrexed resistance in vivo or in vitro. Our results suggest that gastrodin is a potential antitumor agent by reducing survivin in NSCLC.

Survivin degradation by bergenin overcomes pemetrexed resistance.

PURPOSE: Chemoresistance is a primary factor for treatment failure and tumor recurrence in non-small cell lung cancer (NSCLC) patients. The oncoprotein survivin is commonly upregulated in human malignancies and is associated with poor prognosis, but its effect on carcinogenesis and chemoresistance in NSCLC is not yet evident, and to explore an effective inhibitor targeting survivin expression is urgently needed. METHODS: The protumor characteristics of survivin and antitumor activities of bergenin in NSCLC cells were examined by MTS, colony formation assays, immunoblot, immunohistochemistry, and in vivo xenograft development. RESULTS: Survivin was upregulated in non-small cell lung cancer (NSCLC) tissues, while its depletion inhibited NSCLC tumorigenesis. The current study focused on bergenin, identifying its effective antitumor effect on NSCLC cells both in vivo and in vitro. The results showed that bergenin could inhibit cell proliferation and induce the intrinsic pathway of apoptosis via downregulating survivin. Mechanistically, bergenin reduced the phosphorylation of survivin via inhibiting the Akt/Wee1/CDK1 signaling pathway, thus resulting in enhanced interaction between survivin and E3 ligase Fbxl7 to promote survivin ubiquitination and degradation. Furthermore, bergenin promoted chemoresistance in NSCLC cells re-sensitized to pemetrexed treatment. CONCLUSIONS: Survivin overexpression is required for maintaining multiple malignant phenotypes of NSCLC cells. Bergenin exerts a potent antitumor effect on NSCLC via targeting survivin, rendering it a promising agent for the treatment of NSCLC.

Association of LINC00673 rs11655237 polymorphism with pediatric glioma susceptibility in a Chinese population.

BACKGROUND: Previous researches have suggested that LINC00673 rs11655237 C>T polymorphism might be correlated to cancer susceptibility. However, its correlation with pediatric glioma is unknown. Therefore, this study aimed to determine whether LINC00673 rs11655237 C>T polymorphism is correlated with pediatric glioma. METHODS: In total, we included 399 subjects from South China. The Student's t-test was performed to evaluate age differences between glioma cases and controls. Differences in the categorical variables between the two groups were assessed using the χ2 test. A logistic regression was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: We conducted this case-control study to investigate the association between LINC00673 polymorphism and pediatric glioma susceptibility. Our results revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population (CC/CT compared with TT: adjusted OR =2.49, 95% CI: 0.87-7.15, P=0.091). Furthermore, a stratified analysis also indicated LINC00673 rs11655237 C>T polymorphism did not increase the risk of glioma in different subgroups. CONCLUSIONS: Our study revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population. In the future, further exploration of this genetic factor in relation to glioma susceptibility will require a larger sample size to verify the current findings.

The correlation between polymorphisms in the XPC gene and glioma susceptibility in a Chinese pediatric population.

BACKGROUND: A previous study revealed that single nucleotide polymorphisms (SNPs) in coding genes play a key role in tumorigenesis, genetic disorders, and drug resistance. Xeroderma pigmentosum group C (XPC) protein is a key DNA damage recognition factor that is required for maintaining the genomic stability. However, the correlation between XPC polymorphisms and glioma susceptibility is still unclear. Hence, this study aimed to investigate the correlation between XPC polymorphisms and pediatric glioma susceptibility. METHODS: A total of 399 participants (171 glioma patients and 228 controls) were enrolled to evaluate the correlation between XPC polymorphism and pediatric glioma susceptibility. The count data of two groups was analyzed by chi-squared (χ2) test. Moreover, logistic regression was used to assess the strength of XPC polymorphisms associated with glioma susceptibility. RESULTS: We identified that XPC rs1870134 G>C reduced pediatric glioma susceptibility. Compared to participants with rs1870134 GG/GC genotypes, those with rs1870134 CC genotype had a significantly lower risk for glioma [adjusted odds ratio (AOR) =0.10, 95% confidence interval (CI): 0.01 to 0.78, P=0.028]. Patients with 4-5 genotypes have higher risk of glioma than those with 0-3 genotypes (AOR =1.59, 95% CI: 1.04 to 2.43, P=0.031). The stratified analysis showed that the risky effects of rs2228000 CT/TT genotypes and rs2229090 GC/CC genotypes were more predominant among children aged ≥60 months, astrocytic tumors, and clinical stage I. CONCLUSIONS: We found for the first time that XPC polymorphisms had a statistically significant correlation with pediatric glioma susceptibility in a Chinese population. The XPC rs2228000 CT/TT and rs2229090 GC/CC genotypes could both increase the risk of pediatric glioma in subgroups with females, astrocytic tumors, and clinical stage I. The XPC polymorphism has potential to be a useful adjunct method to screen pediatric glioma.

Renal Hemodynamic Changes and Postsurgical Recovery in Children Treated for Ureteropelvic Junction Obstruction.

OBJECTIVE: The aims of the study were to measure renal hemodynamic indexes and to evaluate postsurgical recovery in children diagnosed with obstructive hydronephrosis using color Doppler ultrasound. METHODS: This study enrolled 36 patients with ureteropelvic junction obstruction who underwent Anderson-Hynes pyeloplasty. The peak systolic velocity (PSV) and the resistive index (RI) of the main renal arteries (MRAs) and interlobar renal arteries (IRAs) were measured using color Doppler ultrasound. Renal hemodynamic indexes were measured before surgery and 2, 4, 6, 8, 10, 12, 14, and 16 weeks after surgery. RESULTS: Split renal function and renal parenchymal thickness were positively correlated with PSV and negatively correlated with RI. Anterior-posterior diameter had no significant correlation with PSV or RI. The PSV in MRAs and IRAs were lower than those of the contralateral kidneys but increased after surgery. Anderson-Hynes pyeloplasty was successfully performed in all patients, including one patient whose kidney was removed 16 weeks after surgery. The RI in the MRAs and IRAs were higher than those of the contralateral kidneys but decreased within 2 weeks after surgery. Peak systolic velocity and RI were still atypical 16 weeks after surgery. The hemodynamic index of the nonfunctional kidney did not show improvement after surgery. CONCLUSIONS: Peak systolic velocity and RI were correlated with renal function and renal parenchymal thickness but were not correlated with dilatation of the renal pelvis. Peak systolic velocity increased whereas RI decreased after surgery and were stable at 8 weeks, but remained abnormal 16 weeks after surgery. Hemodynamic measurements may be a useful and convenient method to evaluate surgical outcomes after Anderson-Hynes pyeloplasty.

Enhancement of Colonic Absorptive Function after the Massive Resection of the Small Intestine Based on the Creation of an Artificial Colonic Valve.

The colon can have an absorptive function similar to that of the small intestine after the massive resection of the small bowel. To improve colonic absorptive function, we created a valve in the colon (artificial colonic valve, ACV). ACVs were created in 20 rats that had 80 percent of their small intestine resected, with an observation time of 30 weeks. The ACV rats were compared with those in the non-operated control group, the short bowel syndrome (SBS) group and the colon interposition (CI) group. The ACV rats were much heavier than those in the control group, SBS group and CI group. In terms of histology and the levels of α-amylase and the Na+-dependent bile salt transporter, the absorptive function of the colons before the valves resembled that of the small intestine. The colonic absorptive function was more obvious in ACV rats than in CI rats. An ACV can enhance colonic absorptive function after the massive resection of the small intestine. The colonic absorptive function of ACV rats was better than that of the rats in the CI group.

[Preliminary experimental study on intrauterine abdominal wall defect repair of fetal lamb at late pregnancy].

OBJECTIVE: To evaluate the feasibility of intrauterine abdominal wall defect repair of fetal lamb at late pregnancy. METHODS: Eight healthy pregnant ewes at 110-115 days of gestation (weighing 14-22 kg) were randomly divided into 2 groups. In group A (n = 3), the abdominal wall defect of 5 cm x 1 cm was made in the fetal lambs, then was closed by strengthening suture; in group B (n = 5), the abdominal wall defect of 5 cm x 2 cm was made in the fetal lambs, then was repaired by 2 layers of biological patches. After the lambs delivered naturally, the lambs and their wounds were observed; at 10th day after birth, the scars were harvested for biomechanical and histological observations. RESULTS: One ewe of group A and 2 ewes of group B aborted, while the others were successfully delivered. In group A, the abdominal incisions of 2 lambs healed well with a line-like scar and mild intra-abdominal adhesion, and the scar thickness was 4-5 mm. In group B, the abdominal incisions of 3 lambs did not heal completely with minor intra-abdominal adhesions, and the scar thickness was 3-4 mm. The wound breaking strength was 16, 20 N in group A and 10, 14, and 18 N in group B, respectively. A slight scar was seen in group A; skin ulcer and underlying fibrous connective tissue with inflammatory cell infiltration were seen in group B. CONCLUSION: It was feasible to repair the abdominal wall defect of fetal lamb at late pregnancy in uterine. Small abdominal wall defect can be sutured directly; biological patch can be used to repair larger abdominal wall defect.

Does intervention in utero preserve the obstructed kidneys of fetal lambs? A radiological and pathological study.

OBJECTIVE: Ureteropelvic junction obstruction is a common cause of end-stage pediatric nephropathy. Our aim was to investigate whether in utero decompression can influence its development. METHODS: A silastic tube was tied around the superior segment of the left ureter to cause partial unilateral obstruction in 22 fetal lambs at 75-85 days of gestation. Three weeks later, tubes were removed in 10 of the fetuses. A single sham procedure was performed on 4 control fetuses. Intravenous pyelography (IVP) and pathological evaluations were conducted in obstructed, decompressed and control subjects. RESULTS: IVP revealed damaged renal function in obstructed subjects. Macroscopically, obstructed kidneys were larger but weighed less and had thinned parenchyma. Microscopy revealed cortical cysts of various sizes and interstitial fibrosis. The number of glomeruli was markedly decreased. In contrast, decompressed kidneys were visualized during IVP, and pathological changes were greatly ameliorated. CONCLUSIONS: Relief of obstruction in utero seems to prevent or attenuate development of nephropathy in lambs. Clinical application of this procedure should proceed with caution until further data are obtained.

Renal parenchymal thickness and urinary protein levels in patients with ureteropelvic junction obstruction after nephrostomy placement.

OBJECTIVE: To assess recovery of renal parenchymal thickness and urinary protein levels in patients with severely hydronephrotic kidneys after nephrostomy placement. METHODS: Fourteen patients (median age 1 year, range 6 months-7 years) who underwent nephrostomy placement for unilateral ureteropelvic junction obstruction at our hospital between May 2007 and January 2009 were included in a retrospective analysis. All patients had severe hydronephrosis, with a median parenchymal thickness of 1.8 mm (range 1-2.5 mm). Kidney morphology was examined by ultrasound before the procedure and 1, 2, 3, 4, 6 and 8 weeks after. Urinary proteins (including albumin, immunoglobulin [IgG], alpha2-macroglobulin, alpha1-microglobulin, beta2-microglobulin [beta2-MG] and kappa chain) and creatinine levels were also tested during these follow-up visits. Fifteen healthy children were assessed for urinary protein levels as well and made up the control group. RESULTS: Parenchymal thickness increased within 4 weeks of nephrostomy placement. Kidney volumes were significantly decreased within 2 weeks. No further changes in morphology were detected after 4 weeks. Urinary alpha1-microglobulin and beta2-MG levels decreased to baseline within 1 and 4 weeks, respectively. Urinary albumin, IgG, alpha2-macroglobulin and kappa chain levels decreased gradually after nephrostomy, but did not return to baseline within 8 weeks. CONCLUSIONS: After nephrostomy placement, parenchymal thickness increases within 4 weeks, tubular function returns to normal earlier than glomerular function and glomerular membrane repair is inversely correlated with the severity of damage.

Ureteral triplication combined with right renal ectopia and ureteral cyst.

Ureteral triplication is one of the rarest malformations of the upper urinary tract. We report the case of a 12-year-old girl with right ureteral triplication combined with renal ectopia and ureteral cyst with stenosis at the junction of the ureteral cyst and distal ureter. The ureteral cyst was tailored and tubularized, and the tight junction was removed, as in Hynes-Anderson ureteropyeloplasty; on reevaluation almost 4 years later, kidney function was normal and computed tomography showed a normal kidney and ureter.