A prospective and consecutive study assessing short-term clinical and radiographic outcomes of Chinese domestically manufactured 3D printing trabecular titanium acetabular cup for primary total hip arthroplasty: evaluation of 236 cases.

Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?

BACKGROUND: The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. METHODS: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). RESULTS: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). CONCLUSIONS: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.

Yeast glucan particles: An express train for oral targeted drug delivery systems.

As an emerging drug delivery vehicle, yeast glucan particles (YGPs) derived from yeast cells could be specifically taken up by macrophages. Therefore, these vehicles could rely on the recruitment of macrophages at the site of inflammation and tumors to enable targeted imaging and drug delivery. This review summarizes recent advances in the application of YGPs in oral targeted delivery systems, covering the basic structure of yeast cells, methods for pre-preparation, drug encapsulation and characterization. The mechanism and validation of the target recognition interaction of YGPs with macrophages are highlighted, and some inspiring cases are presented to show that yeast cells have promising applications. The future chances and difficulties that YGPs will confront are also emphasized throughout this essay. YGPs are not only the "armor" but also the "compass" of drugs in the process of targeted drug transport. This system is expected to provide a new idea about the oral targeted delivery of anti-inflammatory and anti-tumor drugs, and furthermore offer an effective delivery strategy for targeted therapy of other macrophage-related diseases.

The clinical-histologic and prognostic characteristics in patients with a second primary non-small-cell lung cancer after a lobectomy.

OBJECTIVES: The goal of this study was to investigate whether an operation can offer survival benefits for patients with a second primary non-small-cell lung cancer (NSCLC) after a lobectomy for a first primary NSCLC and to analyse the characteristics affecting the survival of those patients. METHODS: We performed survival analyses of patients with a second primary NSCLC based on the Surveillance, Epidemiology and End Results program and used propensity score matching to reduce the potential bias and analyse the data. In addition, the primary observational end point was overall survival (OS), and the secondary observational end point was histologic migration. RESULTS: The data from 944 patients were used to perform the main analysis. A total of 36.2% of patients experienced a shift in tumour histologic type between 2 diagnoses of primary NSCLC, and this shift significantly affected OS (P = 0.0065). The median survival time in patients with surgical resection and those without an operation was 52.0 months versus 33.0 months, respectively. Patients with surgical resection at the secondary diagnosis had better survival than those without surgery (5-year OS rate: 48.0% vs 34.0%, P < 0.001). In addition, compared with a pneumonectomy and a sublobar resection, a lobectomy was the optimal surgical procedure for patients diagnosed with a second primary NSCLC after adjusting for other confounders (adjusted hazard ratio: 0.68, P < 0.01). However, in the subgroup analysis, lobar and sublobar resections could provide similar survival benefits for patients with tumour size ≤20 mm (P = 0.5). CONCLUSIONS: The operation, especially a lobectomy, can prolong OS in patients with a second primary NSCLC. Besides, sublobar resection can be performed in selected patients with tumour size ≤20 mm. Moreover, histologic migration may impact the survival of those patients with a secondary primary NSCLC.

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Systematic review and meta-analysis of imaging differential diagnosis of benign and malignant ovarian tumors.

Background: With the increasing incidence of gynecological ovarian tumors, the differential diagnosis of benign and malignant ovarian tumors is of great significance for subsequent treatment. Currently, ovarian examinations commonly use computed tomography (CT) or magnetic resonance imaging (MRI). This study sought to compare the value of CT and MRI in differentiating between benign and malignant ovarian tumors. Methods: The PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and Weipu databases were searched for published articles using the following terms "CT" or "Computed Tomography" or "MRI" or "Magnetic Resonance imaging" and "ovarian cancer" or "ovarian tumor" or "ovarian neoplasm" or "adnexal mass" or "adnexal lesion". The articles were screened and the data were extracted based on the inclusion and exclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies-2 recommended by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and the network meta-analysis was performed by Stata 15.0. Results: The results showed that the overall sensitivity and specificity of CT were 0.79 [95% confidence intervals (CI): 0.70-0.87] and 0.87 (95% CI: 0.80-0.92), respectively. The overall sensitivity and specificity of MRI were 0.94 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.90-0.93), respectively. The area under the curve of the CT and MRI summary receiver operating characteristics were 0.9016 and 0.9764, respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CT were 5.26 (95% CI: 2.78-9.93), 0.26 (95% CI: 0.13-0.50), and 22.19 (95% CI: 7.54-65.30), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of MRI were 8.69 (95% CI: 5.06-14.92), 0.07 (95% CI: 0.04-0.13), and 146.19 (95% CI: 68.88-310.24), respectively. Conclusions: Compared to CT, MRI has a stronger ability to differentiate between benign and malignant ovarian tumors. It's a promising non-radiological imaging technique and a more favorable choice for patients with ovarian tumors. However, in the future, large-sample, multi-center prospective studies need to be conducted to compare the performance of MRI and CT in distinguishing between benign and malignant ovarian tumors.

Luteolin inhibits H2O2-induced cellular senescence via modulation of SIRT1 and p53.

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated ß-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis.

Fowl adenovirus serotype 4 (FAdV-4) strain SD1511 was isolated from chickens with severe inclusion body hepatitis and hydropericardium syndrome in Shandong Province, China. The isolate was cultured in primary chicken embryo kidney cells. A study of pathogenicity indicated that SD1511 readily infected 7-35-d-old chickens by intramuscular injection and intranasal and oral routes, causing 50%-100% mortality. The 35-d-old chickens suffered more severe infection than 7- and 21-d-old chickens with mortality highest in the intramuscular injection group. The serum from surviving chickens showed potent viral neutralizing capability. The complete genome of SD1511 was sequenced and analyzed. The strain was found to belong to the FAdV-4 cluster with more than 99% identity with the virulent FAdV-4 strains isolated in China in recent years except for some distinct variations, including deletions of open reading frame 27 (ORF27), ORF48, and part of ORF19. Our findings suggest that SD1511 might be used as a prototype strain for the study of pathogenesis and vaccine development.

The chemical constituents from Urtica fissa leaves.

A new ceramide urticamide (1), two new secolignans urticalactones I (2) and Ⅱ (3), and a new flavonoid glycoside urticaside (4), together with 15 known compounds (4-19), were isolated from the leaves of Urtica fissa, a folk medicine for rheumatism arthritis in China. The active evaluation results showed that 1, 2, 3, 8, and 13 possessed the potent anti-inflammatory. They could inhibit the release of NO and TNF-α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells, with IC50 values less than 4.0 µM.

Correction: Nur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFα secretion and lowering CSF-1R expression.

[This corrects the article DOI: 10.1371/journal.pone.0171347.].

Nur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFα secretion and lowering CSF-1R expression.

Nur77, an orphan member of the nuclear receptor superfamily, plays critical roles in inflammation and immunity. However, the role of Nur77 in tumor microenvironment remains elusive. Results showed that deletion of Nur77 strikingly enhanced tumor metastasis compared to WT mice. Additionally, compared to the conditioned media derived from Nur77+/+ peritoneal macrophages (CM1), the conditioned media derived from Nur77-/- peritoneal macrophages (CM2) significantly promoted the EMT of cancer cells, and greatly enhanced the migratory and invasive abilities of cancer cells. Moreover, studies using TNF-α blocking antibody demonstrated that pro-inflammatory cytokine TNF-α was indispensable in supporting CM2-induced EMT to drive cancer cells migration and invasion. Furthermore, we found that Nur77 promoted the expression of CSF-1R, a novel downstream target gene of Nur77, and subsequently enhanced the migration of inflammatory cells. Notably, infiltration of inflammatory cells in the tumors of Nur77-/- mice was markedly abrogated compared to Nur77+/+ mice. Collectively, these results revealed that host Nur77 expression was pivotal in antitumor immune response, and in inhibiting tumor metastasis.

Microarray-based identification of differentially expressed genes in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy accounting for approximately 1-2% of vulvar cancers. The rarity of this disease has caused difficulties in characterization and the molecular mechanism underlying EMPD development remains largely unclear. Here we used microarray analysis to identify differentially expressed genes in EMPD of the scrotum comparing with normal epithelium from healthy donors. Agilent single-channel microarray was used to compare the gene expression between 6 EMPD specimens and 6 normal scrotum epithelium samples. A total of 799 up-regulated genes and 723 down-regulated genes were identified in EMPD tissues. Real-time PCR was conducted to verify the differential expression of some representative genes, including ERBB4, TCF3, PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR results were consistent with microarray data, and the expression of ERBB4, PRLR, TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD (P<0.05). Moreover, the overexpression of PRLR in EMPD, a receptor for the anterior pituitary hormone prolactin (PRL), was confirmed by immunohistochemistry. These data demonstrate that the differentially expressed genes from the microarray-based identification are tightly associated with EMPD occurrence.

[Applied research on autologous bone graft for acetabular defect of Crowetype III and IV hip dysplasia].

OBJECTIVE: To study clinical efficacy of autologous bone graft for acetabular defect of Crowe III and IV hip dysplasia. METHODS: The 22 patients with 25 hips of DDH (Crowe type III, IV) from March 2010 to May 2013 were retrospectively analyzed. Total hip arthroplasty (THA) combined autogenous bone grafting was performed for all these patients with osteoarthritis secondary to DDH. Among them, 19 patients were females (21 hips) and 3 patients were males (4 hips), ranging in age from 43 to 67 years old, averaged 55 years old. There were 6 hips with Crowe type III and 19 hips with Crowe type IV. Before surgery, all the patients had hip pain, limb shortening and hip limited function of hip joint. After 12 months, the degree of recovery about limb length, functional recovery, autogenous bone graft fusion were observed. RESULTS: All the patients were followed up and no dislocation were occurred. At 12 months after operation, the average Harris hip joint llzncation score were 83.30±6.13, and 18 cases got an excellent result and 4 good. The length of lower limbs decreased from preoperative (3.20±0.81) cm to 12 months after operation (0.92±0.23) cm (t=14.864, P<0.05). CONCLUSION: THA combined with structural femoral head autograft for patients with osteoarthritis secondary to DDH can obtain favorable results, significantly improving the effect of operation treatment.

[Study on chemical constituents of Euphorbia helioscopia and their antitumor activities].

OBJECTIVE: To investigate the chemical constituents of Euphorbia helioscopia and their antitumor activities. METHODS: Normal phase silica gel, RP-18 silica gel and Sephadex LH-20 column chromatographies combined with recrystallization were used to isolate and purify the constituents. Their structures were identifided by spectroscopic methods, including 1H-NMR, 13C-NMR, ESI-MS and EI-MS. And the antitumor activities of some of chemical constituents in vitro were detected by sulphorhodamine B protein staining. RESULTS: Nine compounds were isolated and their structures were identified as euphohelioscopin A (1), euphoscopin (2), 9, 19-cyclolanost-23E-ene-3, 25-diol (3), euphoscopin C (4), euphornin A (5), euphoheliosnoid A (6), ent-kaurane-3-oxo-16beta, 17-diol (7), 9, 19-cyclolanost-25-ene-3beta, 22-diol (8) and helioscopinolide A(9) Compound 9 showed effect on inhibiting the cell proliferations of MCF-7 cell line. CONCLUSION: Compounds 3, 7, 8 and 9 are obtained from this plant for the first time, and compound 9 shows the potential antitumor activity.

Dual effects of phloretin on aflatoxin B1 metabolism: activation and detoxification of aflatoxin B1.

Typically, chemopreventive agents involve either induction of phase II detoxifying enzymes and/or inhibition of cytochrome P450 enzymes (CYPs) that are required for the activation of procarcinogens. In this study, we investigated the protective effects of phloretin against aflatoxin B1 (AFB1) activation to the ultimate carcinogenic intermediate, AFB(1)-8, 9-epoxide (AFBO), and its subsequent detoxification. Phloretin markedly inhibited formation of the epoxide with human liver microsomes in a dose-dependent manner. Phloretin also inhibited the activities of nifedipine oxidation and ethoxyresorufin O-deethylase (EROD) in human liver microsomes. These data show that phloretin strongly inhibits CYP1A2 and CYP3A4 activities, which are involved in the activation of AFB1. Phloretin increased glutathione S-transferase (GST) activity of alpha mouse liver 12 (AML 12) cells in a dose-dependent manner. GST activity toward AFBO in cell lysates treated with 20 µM phloretin was 23-fold that of untreated control cell lysates. The expression of GSTA3, GSTA4, GSTM1, GSTP1 and GSTT1 was induced by phloretin in a dose-dependent manner in AML 12 cells. GSTP1, GSTM1, and GSTT1 were able to significantly increase the conjugation of AFBO with glutathione. Concurrently, induction of the GST isozyme genes was partially associated with the Nrf2/ARE pathway. Taken together, the results demonstrate that phloretin has a strong chemopreventive effect against AFB1 through its inhibitory effect on CYP1A2, CYP3A4, and its inductive effect on GST activity.

Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells.

Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.

Sulforaphane induces glutathione S-transferase isozymes which detoxify aflatoxin B(1)-8,9-epoxide in AML 12 cells.

The aflatoxin B(1)-8,9-epoxide (AFBO) is hepatocarcinogenic intermediate of aflatoxin B(1) (AFB(1)) and is detoxified by glutathione S-transferases (GSTs). In this study, we investigated whether sulforaphane (SFN) could increase the rate of conjugation between AFBO and glutathione (GSH) as well as which of the GST isozymes were involved in the conjugation reaction. The conjugation potential was inhibited dose dependently with curcumin, an inhibitor of GSTs. SFN induced the expression of GST A3, GST A4, GST M1, GST P1, and GST T1 in alpha mouse line (AML) 12 cells. The cells treated with SFN (10 microM) for 12 h showed a 35-fold increase in conjugation potential of AFBO with GSH compared with the vehicle-treated cell. The conjugation potential was blocked partially by transfection of cells with siRNAs against each of the GST isozymes. The activity of GST A3 had the strongest effect on the conjugation potential. SFN treatment also increased total GST activity detected with 1-chloro-2,4-dinitrobenzene (CDNB) up to 4.3-fold. The induction fold was much lower than that detected with AFBO. These results suggest that the chemopreventive effect of SFN on the decomposition of AFBO is related to the upregulation of several GST isozymes genes. The increase of GST activity by SFN was extremely specific toward the conjugation reaction of AFBO compared with CDNB. Therefore, this system for detecting GST activity seems to be an excellent method for screening chemopreventive compounds toward AFB(1) toxicity.

Kaempferol suppresses cisplatin-induced apoptosis via inductions of heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit in HEI-OC1 cell.

PURPOSE: The present study was undertaken to elucidate the chemoprotective mechanism of kaempferol, which possesses anti-oxidative and anti-apoptotic properties. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with kaempferol in the presence or absence of cisplatin. Cisplatin-induced oxidative stress was assessed by analysis of Comet assay, DNA-laddering assay and activation of caspases. Heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK) pathway and nuclear factor-E2-related factor 2 (Nrf2) were measured by Western blot analysis. Transfection of small interfering RNAs (siRNA), glutathione (GSH) assay and RT-PCR were performed in this study. RESULTS: Kaempferol protected cells against cisplatin-induced apoptosis in a dose-dependent manner in HEI-OC1 cells. Kaempferol-induced HO-1 expression protected against cell death though the c-Jun N-terminal kinase (JNK) pathway and by the aid of Nrf2 translocation. Kaempferol increased the cellular level of GSH and the expression of GCLC time-dependently. siRNA GCLC blocked the increase of GSH level by kaempferol and the protective effect of kaempferol against cisplatin-induced cell death. CONCLUSION: The expression of HO-1 by kaempferol inhibits cisplatin-induced apoptosis in HEI-OC1 cells, and the mechanism of protective effect is also associated with its inductive effect of GCLC expression.