Effective Model of Food Allergy in Mice Sensitized with Ovalbumin and Freud's Adjuvant.

To better explore the pathophysiology of FA and its therapy, we aimed to establish a simple and practicable FA model with Freund's adjuvant and introduce an easy and reliable laboratory evaluation method for assessment of inflammation in intestinal segments at different anatomical locations. BALB/c mice were sensitized with ovalbumin combined with Freund's adjuvant. Complete Freund's adjuvant was chosen for the first sensitization and two weeks later incomplete Freund's adjuvant was used for a second sensitization. Two weeks later, the sensitized mice were challenged with 50 mg ovalbumin every other day. After the 6 challenge, all mice were assessed for systemic anaphylaxis, and then sacrificed for sample collection. All sensitized mice showed anaphylactic symptoms and markedly increased levels of serum ovalbumin-specific IgE and IgG1. The activity of mast cell protease-1 (mMCPT-1) was significantly increased in the serum and interstitial fluid of the duodenum, jejunum, ileum, and colon. A successful FA model was established, of which inflammation occurred in the duodenum, jejunum, ileum, and colon. This model provides a reliable and simple tool for analysis of the mechanism of FA and methods of immunotherapy. Moreover, combined detection of ovalbumin-specific antibody and local mMCPT-1 levels could potentially be used as the major indicator for assessment of food allergy.

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.

Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B-mediated NMDA currents and extrasynaptic responses that were induced by bursts of high-frequency stimulation, which may be associated with the loss of astrocytes and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in the mPFC was sufficient to induce depressive-like behavior and cause similar molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno-associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also rescued CUS-induced depressive-like behavior 7 days after treatment. A selective GluN2B antagonist did not have rewarding effects in the conditioned place preference paradigm. Altogether, our findings suggest that the DAPK1 interaction with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology of depression and is a potential target for new antidepressant treatments.

Fusion protein tTF-EG3287 induces occlusion of tumor vessels and impairs tumor growth in human colon caner.

The problems including narrow indications, low drug loading, and difficulty in intervention severely affect the clinical efficacy of anti-tumor embolization. Here, we designed a novel tTF-EG3287 protein consisting of the truncated tissue factor (tTF) fused with the bicyclic polypeptide which was encoded by exons 7 and 8 for accurate localization in the tumor vascular endothelial cells (EG3287). This study aims to explore its anti-cancer effect. Gene sequencing was used to verify the fusion gene and SDS-PAGE gel to confirm the optimal induction time and concentration of tTF-EG3287. Nickel affinity chromatography column was used to purify the fusion protein. Confocal microscopy was used to assess the target activity of tTF-EG3287 on colon cancer cells in vitro. Thrombelastography assay was used to identify the pro-coagulant activity of tTF-EG3287. In in vivo experiments, the specific localization of tTF-EG3287 in tumor tissues and the effect of tTF-EG3287 on tumor thrombosis were further detected by in vivo imaging and HE staining, respectively. The tTF-EG3287 fusion protein was efficiently purified by nickel-affinity chromatography column. Moreover, tTF-EG3287 fusion protein showed strong coagulation a ctivity and specific binding ability to the cell surface of colon cancer. In vivo, tTF-EG3287 stably and persistently accumulated in tumor tissues, and specifically induced mixed thrombus formation in tumor vessels, and then impaired tumor growth (tumor inhibition rate=79.2%, p<0.01). Our data prove that the fusion protein tTF-EG3287 could be used as a novel and promising anti-cancer strategy and has great potential value for clinical applications.

[Mid-term efficacy of laparoscopic sacral colpopexy of combined transabdominal-transvaginal approach in the treatment of stage â £ pelvic organ prolapse].

Objective: To evaluate the clinical effect after laparoscopic sacral colpopexy (LSC) of combined transabdominal-transvaginal approach on stage Ⅳ pelvic organs prolapse (POP). Methods: The clinical data of 65 patients undergoing LSC of combined transabdominal-transvaginal approach from January 1st, 2010 to July 30th, 2017 due to POP stage Ⅳ in First Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. Objective outcome was assessed by comparing preoperative and postoperative pelvic organ prolapse quantification (POP-Q) systems. Subjective effects were assessed by comparing pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire short form (PFIQ-7), pelvic organ prolapse/urinary incontinence sexual questionnaire-12 (PISQ-12) and patient global impression of improvement (PGI-I). Results: All 65 patients were successfully performed without any intraoperative complications. Fifty-three patients were followed in the clinic department and 12 were followed up by telephone. The follow-up duration was 6.1-80.3 months and the median follow-up duration was 24.5 months. The bleeding loss was 20-250 ml. Postoperative urethral catheter residence day was (2.5±1.1) days, length of postoperative stay was (6.2±1.7) days. The postoperative POP-Q scores were compared with preoperative scores which had significantly improved except pb (all P<0.01). The objective cure rates of vaginal anterior wall, apical and posterior wall prolapse stage Ⅳ were 90% (47/52), 100% (23/23) and 95% (20/21).About PGI-I, except for 1 patient who chose "improvement" , the other 64 patients (98%, 64/65) all chose "significant improvement" . Furthermore, preoperative and postoperative PFDI-20, PFIQ-7, and PISQ-12 scores were all statistically significant (all P<0.01). Subjective efficacy was significant. Three cases (5%, 3/65) of postoperative fever occurred. Two cases (4%, 2/53) had mesh exposure. Six patients (11%, 6/53) had recurrence of postoperative prolapse. Five cases had recurrence of vaginal anterior wall prolapse and no reoperation was performed; 1 case was recurrence of posterior vaginal wall prolapse who diagnosed as vaginal posterior wall prolapse stage Ⅲ; no recurrence of apical prolapse. The rate of reoperation (including exposed-mesh removal and pelvic floor reconstruction surgery) was 5% (3/65). Conclusions: The LSC of combined transabdominal-transvaginal approach has a high subjective efficacy rate. The objective cure rate in the case of apical prolapse stage Ⅳ is one hundred percent.The LSC of combined transabdominal-transvaginal approach has low mesh exposure, low postoperative infection and the reoperation rate, which is one of optional pelvic floor reconstruction surgery. However, there is still a risk of recurrence in patients with POP stage Ⅳ with severe bladder bulging.

Dust mite allergen, glutathione S-transferase, induces T cell immunoglobulin mucin domain-4 in dendritic cells to facilitate initiation of airway allergy.

BACKGROUND: Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. OBJECTIVE: This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. METHODS: The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. RESULTS: Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. CONCLUSION: Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME.

Forkhead box protein-3 (Foxp3)-producing dendritic cells suppress allergic response.

BACKGROUND: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be upregulated by Staphylococcal enterotoxin B (SEB). METHODS: The expression of Foxp3 by DCs was evaluated by real-time RT-PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay. RESULTS: We observed that mice treated with SEB at 0.25-0.5 µg/mouse showed high frequencies of transforming growth factor (TGF)-ß-producing CD4+ T cells and TGF-ß-producing DCs in the intestine, while the IL-4+ CD4+ T cells and TIM4+ DCs were dominated in the intestine in mice treated with SEB at 1-10 µg/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF-ß promoter locus. The function of Foxp3 was blocked by STAT6 (signal transducer and activator transcription-6); the latter was induced by exposing DCs to SEB in the culture at doses of 100-400 ng/ml. Treating allergic mice with specific immunotherapy (SIT) together with SEB significantly promoted the therapeutic effects on the allergic responses than treating with SIT alone. CONCLUSION: Dendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.

Environmental risk factors for women with polycystic ovary syndrome in china: a population-based case-control study.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease with heterogeneous phenotype. Environmental factors are thought to be involved in the development of PCOS. The present study aimed to explore the potential environmental risk factors of PCOS. A cross-sectional study and stratified population-based case-control study were carried out. Pre-designed questionnaires were prepared, including questions about medication history, contact history of endocrine disruptors (EDs), environment and habituation. Fasting blood was collected for measurement of sex hormone, glucose and insulin. Matched logistic regression analysis was used to find the potential independent risk factor of PCOS. One thousand eight hundred fifty-four participants (aged 12-44 years) were analyzed in the cross-sectional investigation. One hundred sixty-nine PCOS patients and 338 matched controls were compared. PCOS patients were more frequent than controls in eating plastic-packaged food (p=0.001), contacting pesticide (p=0.021), eating fruit with pericarp (p=0.001), living beside a garbage heap (p=0.001), working at an acid plant (p=0.028), taking Chinese patent drugs (p=0.001), smoking (p=0.028) and drinking alcohol (p=0.001). However, PCOS patients were less likely to use kitchen ventilators (p=0.002), eat canned food (p=0.049), contact decorated materials, use skin care products (p=0.01) and cosmetics (p=0.027). No difference was found in taking antiepileptic drugs (p=0.93). Eating plastic-packaged food (p=0.001, OR=44.449), eating fruit with pericarp (p=0.03, OR=5.7) and drinking alcohol (p=0.001, OR=29.632) were found to be the independent risk factors for PCOS. The existence of an association between EDs and PCOS was proved. Plastic-packaged food, fruit with pericarp and drinking alcohol should be avoided as possible as we can. However, the causal relationships among these factors and PCOS should be proved by further research.

Author Correction: Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (11): 5264-5279. DOI: 10.26355/eurrev_202306_32646-PMID: 37318501-published online on June 13, 2023. After publication, the authors applied a correction in the Funding section. The section has been amended as follows: This study was supported by a grant from the National Natural Science Foundation of China (No. 81671421). Moreover, the corresponding author's name was wrong. Therefore, in accordance with the email address, the correct corresponding author has been corrected from D.-H. LU to L.-Z. XU. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32646.

Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone replacement therapy (HRT). MATERIALS AND METHODS: Full-text articles published up to April 30, 2021, were searched through PUBMED, EMBASE, the Cochrane library and Web of Science (WOS) databases and were screened strictly according to inclusion criteria. Randomized clinical trials and case control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. Data are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random effect models were used for the meta-analysis. RESULTS: HRT administration increases estradiol (E2) and reduces follicle stimulating hormone (FSH) serum levels compared with pre-treatment. Their changes are evident when oral and transdermal HRT are administered, while vaginal HRT not. No significant effect on E2 and FSH was found between 6 and 12 months, as well as between 12 and 24 months. No significant effect on E2 and FSH was shown between different regimes. No difference was observed between different HRT regarding their effect on lipid profiles, breast pain and vaginal bleeding, but oral estrogen combined synthetic progestin caused a reduction in sex hormone-binding globulin (SHGB). CONCLUSIONS: The review suggested oral and transdermal HRT could lead to a rise in E2 serum levels and a decrease in FSH. The types and doses of HRT did not seem to modify the E2 and FSH level. Also, oral estrogen combined synthetic progestin could cause a reduction in SHGB. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

1073 nm continuous-wave Nd:YVO4 laser with Type I phase-matching LiB3O5.

Continuous output from a Nd:YVO4 crystal around 1073 nm was studied. The output of 1064 nm was suppressed with a Type I phase-matching LiB3O5 (LBO) crystal rotated by 45°. With a pump power of 4.5 W, a 300 mW continuous output at 1073 nm was achieved for what we believe is the first time, and the optical-to-optical efficiency was 7%. With an adjustable LBO crystal, the wavelength is tunable from 1073.2 to 1073.5 nm. Even simultaneous output of 1066 and 1073 nm was realized by adjusting the LBO crystal. The experiments proved related theoretical analysis.

[Mixed reality technology in fibula flap preparation clinical teaching application].

Objective: To explore the effect of the application of mixed reality (MR) technology in clinical teaching of fibular flap preparation. Methods: Twenty residents from the Department of Oral and Maxillofacial Surgery in School of Stomatology, the Fourth Military Medical University in 2018 and 2019 participated in the present study. They were randomly divided into two groups according to the method of random drawing. The teaching content of the two groups was fibular flap preparation. The MR group was taught by using the new teaching mode which was mainly based on MR, while the conventional teaching group was educated by conventional teaching method. At the end of the training, the theoretical knowledge and operational skills of the residents were statistically analyzed to evaluate the learning effect. Questionnaire survey was also conducted. Each item in the questionnaire was scored between 0 and 5, representing poor to excellent. Results: The theoretical scores of MR group (91.4±4.4) were higher than that of the conventional teaching group (83.3±3.2) (P<0.01). The durations of preoperative marking and simulated osteotomy in MR group [(5.7±1.2) and (20.9±2.28) min, respectively] were shorter than those in the conventional teaching group [(7.2±1.7) and (26.1±3.6) min, respectively] (P<0.05). The results of the questionnaire showed that MR group had a significant improvement in the scores of classroom atmosphere, satisfaction, three-dimensional construction, theoretical knowledge and problem-solving ability (P<0.01). However, there was no statistically significant difference in scores of learning concentration between the two groups (P>0.05). Conclusions: The application of MR technology achieved a better teaching effect, which could help residents to deeply understand the methods of fibular flap preparation, and showed a broad application prospect.

Evaluation of multiple sclerosis diagnostic criteria in Suzhou, China--risk of under-diagnosis in a low prevalence area.

OBJECTIVE: To evaluate the discharge diagnosis of demyelinating diseases in the central nervous system (CNS) and analyze the predictive value of the new diagnostic criteria in Suzhou, China. MATERIALS AND METHODS: We collected clinical information and data of laboratory examinations for all cases with a diagnosis of various demyelinating diseases in the CNS. All data were reviewed individually by four senior neurologists, and a diagnosis was finally given to each patient according to the McDonald criteria and the Poser criteria for multiple sclerosis (MS). RESULTS: In the analysis, 176 patients with a diagnosis of demyelinating diseases in the CNS at discharge were included. In 82 patients with a diagnosis of MS at discharge, the MS diagnosis was confirmed for 74 patients according to the McDonald criteria for MS, and the positive predictive value for the discharge diagnosis of MS was 90.2% (74/82). According to the Poser criteria, 61 patients were diagnosed as MS. The consistency of the two diagnostic criteria for MS was 78.4%, based on the results of the evaluation. CONCLUSIONS: Under-diagnosis of MS could be one of the explanations for the low prevalence of MS in China. Compared to the Poser criteria, the McDonald criteria had a higher sensitivity for the diagnosis of MS.

RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6.

OBJECTIVE: RBBP6 is identified to be a cancer-associated gene by bioinformatics analysis. This study aims to explore the role of RBBP6 in regulating proliferation and metastasis in ovarian cancer, thus providing theoretical references for ovarian cancer treatment. PATIENTS AND METHODS: Differential expressions of RBBP6 in ovarian cancer and normal ones were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between RBBP6 and prognosis in ovarian cancer patients was analyzed. The interaction between RBBP6 and PIK3R6 was detected by bioinformatics analysis and Dual-Luciferase reporter assay. Moreover, regulatory effects of RBBP6 and PIK3R6 on proliferative and migratory potentials in A2780 and CAOV3 cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Finally, tumorigenicity assay was conducted in nude mice to illustrate the in vivo regulations of PBBP6 and PIK3R6 on ovarian cancer growth. RESULTS: RBBP6 was upregulated in ovarian cancer tissues than normal ones. RBBP6 was irrelevant to age, tumor size and tumor node metastasis (TNM) staging in ovarian cancer patients, but correlated to lymphatic metastasis and distant metastasis. RBBP6 was abundantly expressed in ovarian cancer cells, and among the tested cell lines, CAOV3 and A2780 expressed the highest level of RBBP6. Knockdown of RBBP6 attenuated in vitro proliferative and migratory potentials in CAOV3 and A2780 cells. PIK3R6 was the target gene binding RBBP6, which was positively regulated by RBBP6. Overexpression of PIK3R6 could abolish the inhibited proliferative and migratory potentials in ovarian cancer cells with RBBP6 knockdown. In addition, the knockdown of RBBP6 slowed the in vivo growth of ovarian cancer in nude mice, and the alleviated cancer progression was reversed by overexpression of PIK3R6. CONCLUSIONS: RBBP6 is highly expressed in ovarian cancer cases, which stimulates proliferative and migratory potentials by targeting PIK3R6. RBBP6 may be a novel therapeutic target for ovarian cancer.

Mitochondrial modulation is involved in the hepatoprotection of Limonium sinense extract against liver damage in mice.

AIM OF THE STUDY: Limonium sinense (Girard) Ktze is a Chinese folk medicine used to treat fever, hemorrhage, hepatitis, and other disorders. The present research focused on the protective effects of L. sinense extracts (LSE) against liver damage. MATERIALS AND METHODS: In this study the extract from the root of Limonium sinense was used. Aminotransferase activity detection, electron microscopy, mitochondrial function evaluation, RT-PCR and western blot were used to evaluate the hepatoprotection of LSE in LPS/d-GalN-intoxicated mice. RESULTS: Pretreatment with 100, 200 or 400mg/kg LSE significantly blocked the increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels induced by treatment with LPS plus d-GalN (LPS/d-GalN). Ultrastructural observation by electron microscopy showed reduced hepatocyte nuclear condensation and less lipid deposition. The decrease in both the mitochondrial membrane potential (14.6%) and sensitivity to mitochondrial swelling induced by Ca(2+) (45.9%) observed in the liver of LPS/d-GalN-treated mice were prevented by pretreatment with LSE. In addition, different doses of LSE increased both the transcription and the translation of voltage-dependent anion channels (VDAC), which was down-regulated by LPS/d-GalN treatment. CONCLUSIONS: In summary, LSE protects livers against LPS/d-GalN-induced damage, possibly by mitochondrial mechanisms related to increased expression of VDAC.

Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.

Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.

Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.

This corrects the article DOI: 10.1038/onc.2017.368.

Stat1 serine phosphorylation occurs independently of tyrosine phosphorylation and requires an activated Jak2 kinase.

Gamma interferon (IFN-gamma) induces both tyrosine and serine phosphorylation of Stat1. Stat1 serine phosphorylation is required for maximal transcriptional activity of Stat1. In this report, we present evidence that Stat1 tyrosine phosphorylation is not a prerequisite for Stat1 serine phosphorylation, although an active Jak2 kinase is required for both phosphorylation events. Stat1 serine phosphorylation occurs with a more delayed time course than tyrosine phosphorylation. The occurrence of serine phosphorylation without tyrosine phosphorylation suggests that serine phosphorylation takes place in the cytoplasm. Experiments performed with cells expressing either dominant-negative or constitutively active Ras protein indicated that the Ras-mitogen-activated protein kinase pathway is probably not involved in IFN-gamma-induced Stat1 serine phosphorylation. Finally, a kinase capable of correct Stat1 serine phosphorylation was detected in partially purified cytoplasmic extracts from both IFN-gamma-treated and untreated cells.

p62/SQSTM1 enhances breast cancer stem-like properties by stabilizing MYC mRNA.

Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24- fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.

Phenotypic expression of non-Hodgkin's lymphomas in China.

Monoclonal antibodies were used to label malignant lymphomas obtained from 57 patients. On the basis of morphologic criteria, 18 lymphomas were the B-cell type, 10 were the T-cell type, and 6 were histiocytic; for 23 the type could not be determined. After monoclonal antibody labeling, 18 lymphomas of B-cell lineage were confirmed, 16 of the T-cell type were demonstrated, 6 were true histiocytic, and 17 were the null cell (non-T, non-B) type. Of the 16 lymphomas of T-cell lineage, 6 were lymphoblastic and 10 were the peripheral type. The percentages of cell types in the non-Hodgkin's lymphomas were as follows: B-cell, 31.5%; T-cell, 28%; null cell, 29%; and histiocytic, 10%. Of the 16 lymphomas of T-cell origin, 15 belonged to helper T-cell subsets (Leu1+, Leu4+, and Leu3a+), and the la marker was positive in all 16. Of the 18 B-cell lymphomas, 14 were kappa-positive and 4 were lambda-positive. Eleven were both B1- and kappa-positive, and 1 was kappa-positive but B1-negative. In the 4 cases that were lambda-positive, 2 were both lambda- and B1-positive. The results indicate that Leu4, Leu2a, Leu3a, and B1 are the most important markers to differentiate T-cell and B-cell lymphomas for pathologic classification. The findings also show a higher percentage of T-cell neoplasm in China as compared to that in Western countries.

Xanthones from the stems of Securidaca inappendiculata.

From the stems of Securidaca inappendiculata, securixanthones A (1,3,7-trihydroxy-2,8-dimethoxyxanthone) and B (3,7-dimethoxy-4-hydroxyxanthone) along with ten known xanthones were isolated. Their structures were elucidated by analysis chemical and spectroscopic evidence, and the chemotaxonomic significance of these findings are also discussed.