[Help-seeking efficacy and the intention of social assistance among medical care personnel during the major public health events].

Objective: To explore the help seeking efficacy and social assistance willingness of medical staff during major public health events, so as to provide basis for improving the psychological resources and service quality of medical staff and further optimizing the prevention and treatment policies. Methods: In February 2020, a convenient sampling method was used to conduct an online questionnaire survey on medical staff in Henan Province, and a total of 2136 questionnaires were collected. Among them, there were 1940 valid questionnaires, and the effective recovery rate was 90.82%. The questionnaire of help seeking efficacy and willingness to social assistance under epidemic situation was used to investigate the help seeking efficacy and willingness of medical staff. The frequency and rate (%) were used to analyze the overall situation of medical staff's help seeking efficacy and social assistance willingness. The differences among different demographic variables were tested by χ(2) test. Results: Among the 1940 medical and nursing staff, 18.81% (365/1940) did not know how to obtain appropriate psychological assistance. Compared with the low age group, the medical staff in the high age group had the ability of information query, the ability to occupy knowledge resources, the ability to distinguish rumors and facts and the sense of efficacy of obtaining appropriate medical help, and the difference was statistically significant (P<0.05) . The willingness of medical and nursing staff to actively cooperate with the government, maintain social stability and volunteer work were 99.43% (1929/1940) , 98.81% (1917/1940) and 97.11% (1884/1940) . Conclusion: The medical staff had a higher sense of help seeking efficacy and willingness to social assistance. It is necessary to further strengthen the resource support of psychological, social and humanistic care for medical staff.

Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case-control study.

BACKGROUND: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. OBJECTIVE: To investigate the impact of early-life infections on AD development. METHODS: This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. RESULTS: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. CONCLUSION: Infections in early life are associated with AD development in infancy and early childhood.

Executive Function Predicts the Validity of Subjective Memory Complaints in Older Adults beyond Demographic, Emotional, and Clinical Factors.

BACKGROUND: Although evidence suggests that subjective memory complaints (SMCs) could be a risk factor for dementia, the relationship between SMCs and objective memory performance remains controversial. Old adults with or without mild cognitive impairment (MCI) may represent a highly heterogeneous group, based partly on the demonstrated variability in the level of executive function among those individuals. It is reasonable to speculate that the accuracy of the memory-monitoring ability could be affected by the level of executive function in old adults. OBJECTIVE: This study investigated the effects of executive function level on the consistency between SMCs and objective memory performance while simultaneously considering demographic and clinical variables in nondemented older adults. SETTING: Participants were recruited from both the memory clinics and local communities. PARTICIPANTS: Participants comprised 65 cognitively normal (CN) older adults and 54 patients with MCI. MEASUREMENTS: Discrepancy scores between subjective memory evaluation and objective memory performance were calculated to determine the degree and directionality of the concordance between subjective and objective measures. Demographic, emotional, genetic, and clinical information as well as several executive function measurements were collected. RESULTS: The CN and MCI groups exhibited similar degrees of SMC; however, the patients with MCI were more likely to overestimate their objective memory ability, whereas the CN adults were more likely to underestimate their objective memory ability. The results also revealed that symptoms of depression, group membership, and the executive function level together predicted the discrepancy between the subjective and objective measures of memory function; however, the executive function level retained its unique predictive ability even after the symptoms of depression, group membership, and other factors were controlled for. CONCLUSION: Although both noncognitive and cognitive factors were necessary for consideration, the level of executive function may play a unique role in understanding the equivocal relationship of the concurrence between subjective complaints and objective function measures. Through a comprehensive evaluation, high-risk individuals (i.e., CN individuals heightened self-awareness of memory changes) may possibly be identified or provided with the necessary intervention during stages at which objective cognitive impairment remains clinically unapparent.

TT genotype of rs10036748 in TNIP1 shows better response to methotrexate in a Chinese population: a prospective cohort study.

BACKGROUND: Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. OBJECTIVES: To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. METHODS: A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single-nucleotide polymorphisms in 14 susceptibility genes, and HLA-Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. RESULTS: Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. CONCLUSIONS: Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.

Nucleic Acid Tests for BK Polyomavirus Is Critical in Renal Transplant Recipients.

This study evaluates the incidence of BK polyomavirus (BKV) and prognosis of BKV infection in kidney transplant recipients (KTRs) who received transplantation in our hospital before and after regular BKV nucleic acid test (NAT) was implemented. METHODS: The study included 74 KTRs who received a single kidney either from standard- or expanded-criteria deceased donor between March 2011 and March 2017. BKV NATs were regularly checked in 26 patients (group 1) in the first posttransplant year in accordance with current guidelines since NAT was implemented in our laboratory in 2014. We retrospectively compared 48 KTRs (group 2) who either received NAT when necessary in another laboratory or were not checked before 2014. RESULTS: There was no significant difference in patient characteristics between groups. BKV viruria were confirmed in 8 of 26 (30.8%) group 1 patients, whereas only 2 of 48 (4.2%) BKV infections were confirmed in group 2. None of the BKV(+) KTRs in group 1 developed BK polyomavirus-associated nephropathy (BKVAN), whereas 2 BKV(+) patients (100%) of group 2 developed BKVAN, which indicates renal function deterioration and biopsy-validated nephropathy. There was no significant difference in graft survival and renal function between the 2 groups. CONCLUSIONS: The risk of BKV infection is considerably higher in KTRs using NAT. Because there is no approval treatment, early diagnosis of BKV infection and early reduction of immunosuppression agents is critical for KTRs. Implementation of regular BKV NAT is mandatory before BKVAN and malignant neoplasms develop.

Protective effect of tauroursodeoxycholic acid on the autophagy of nerve cells in rats with acute spinal cord injury.

OBJECTIVE: To investigate the impact and protective effect of tauroursodeoxycholic acid (TUDCA) on the autophagy of nerve cells in rats with acute spinal cord injury. MATERIALS AND METHODS: Seventy-two 6-8-week-old male Sprague-Dawley (SD) rats were selected and were randomly divided into a sham operation group, a saline control group and a TUDCA treatment group (high and low dose groups). The experimental animals were sacrificed at 24 hours, 5 days and 10 days after spinal cord injury. The Basso, Beattie, Bresnahan locomotor scale was used to assess the hind limb locomotor function after the rats were injured but before sudden death. Electron microscopy, hematoxylin and eosin (HE) staining, TUNEL assays and immunohistochemistry techniques were used to observe the autophagy of the cells. Western blotting was used to analyze the expression of the autophagy-related factor Beclin-1 and the apoptosis-related factor caspase-3, and reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the above proteins. RESULTS: The locomotor scores of the rats in the saline group were significantly reduced, their Beclin-1 expression levels in neurons were decreased, and caspase-3 expression was increased. The hind limb locomotor scores of rats in the TUDCA groups were decreased, with no difference between the high- and low-dose groups. Beclin-1 expression in their neurons was increased, and caspase-3 expression was decreased; there was a significant difference when compared with the control group, while there was no significant difference between the high- and low-dose groups. CONCLUSIONS: TUDCA significantly activates the neuronal autophagic expression in rats with acute spinal cord injury to inhibit the apoptosis of nerve cells; therefore, it has a protective effect on neurons.

Noninvasive quantitative analysis of ceramide in skin of healthy Chinese population.

OBJECTIVE: The objective of this study was to make noninvasive quantitative analysis of ceramide (CER) in skin of healthy Chinese population by high performance liquid chromatography tandem mass spectrometry. METHODS: Seven healthy subjects were selected and the stratified skin samples were available using cyanoacrylate adhesion method. High performance liquid chromatography tandem mass spectrometry, use ceramide Subclass Standard C42H85NO3 Quantification of the 12 corresponding ceramide subclass in the epidermis on the 7 skin samples, which cannot get all the standard of ceramides subclass since the stratum corneum ceramide is complex and diverse. Data were collected and analyzed using full-flow lipid analysis software (LipidSearch). RESULTS: All the seven skin samples contained 12 subclasses of ceramide and the samples were quantitated with ceramide C42H85NO3 standard. The average contents were 33.63, 27.59, 108.57, 220.75, 149.20, 43.06, and 22.78 µg/mL, respectively. CONCLUSION: Ceramide is an important lipid in the epidermis and is closely related to the skin barrier function. There are 12 subtypes of ceramide detected in the skin of Chinese healthy people, and there is a difference in the concentration between individuals. The difference may be associated with the skin barrier condition, and may also be related to the unavoidable error in the process of sampling, treatment, and detection.

A real-time prediction model for post-irradiation malignant cervical lymph nodes.

OBJECTIVE: To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. METHODS: One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. RESULTS: A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05). CONCLUSIONS: A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation.

Clinical research on airway intervention before tracheal extubation after general anesthesia on snoring children.

OBJECTIVE: To analyze the method and the effect of airway intervention before tracheal extubation in post-anesthesia cure unit (PACU) after anesthesia when removing the tonsil under general anesthesia and adenoidectomy under nasal endoscope on children with snoring. PATIENTS AND METHODS: 46 cases diagnosed as snoring were executively selected in this study. The cases were randomly divided into the control group (n = 22) and the observation group (n = 24). For airway intervention after general anesthesia during the recovery period, the control group was treated with intravenous injection of 0.5 µg/kg remifentanil, whereas the observation group was treated with atomization inhalation of 15 mg ambroxol hydrochloride and 0.5 mg budesonide suspension. RESULTS: The clinical effects of both methods were compared and analyzed for statistical analysis. The blood pressure, heart rate and blood oxygen saturation at 30 min and 10 min after extubation in the control group was significantly more stable than those in the observation group (p < 0.05). The alertness/sedation (OAA/S) score in the observation group was significantly higher than that in the control group (p < 0.05). The prevalence rate of complications after extubation in the two groups was not statistically significant (p > 0.05). The levels of serum cortisol (Cor) and IL-8 in the control group were significantly lower than those in the observation group (p < 0.05). CONCLUSIONS: Both methods are effective for treatment of airway intervention concerned with snoring children after general anesthesia during the recovery period. The effect of remifentanil on hemodynamics is relatively huge compared with that of atomization inhalation.

GSK3ß controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug.

This corrects the article DOI: 10.1038/onc.2013.279.

Effects of mulberry leaves on production performance and the potential modulation of antioxidative status in laying hens.

This study evaluated the antioxidant ability of Taisung No. 3 mulberry leaf extract (MLE) as well as the potential of mulberry leaf (ML)-based dietary supplementation for modulating the antioxidative status of laying hens. The results showed that the MLE had a total phenolic compound content of 7.4 ± 0.15 mg of gallic acid equivalent/g dry weight (DW) and a total flavonoid content of 4.4 ± 0.19 mg of quercetin equivalent/g DW. The 2, 2-diphenyl-1-picrylhydrazyl free-radical-scavenging ability was 45.9% when 0.1 mg/mL MLE was added. The lipid oxidation inhibition ability was 43.9% when 50 mg/mL MLE was added. We subjected 96 laying hens (Hendrix Genetics) to 4 treatments, namely diets supplemented with dry ML at 0 (control), 0.5, 1, or 2% for 12 weeks. Each treatment involved 8 replicates with 3 hens each. The results indicated that the 0.5% ML-supplemented group exhibited significantly higher mRNA levels of antioxidant-regulated genes, such as Nrf2, HO-1, and GST, and significantly lower ROMO1 gene expression levels at wk 12. The serum malondialdehyde level was lower and the catalase activity and superoxide dismutase activity were higher in all the ML-supplemented groups than in the control group. The egg mass and feed conversion rate significantly improved in the ML-supplemented groups compared with the control group, and, overall, 1% ML supplementation had the most favorable effects at one to 12 weeks. The egg yolk weight, shell weight, shell strength, shell thickness, yolk color, and Haugh unit were increased among all ML-supplemented groups at one to 12 weeks. On the basis of these observations, we conclude that 0.5% ML can be used as a new feed additive to potentially modulate the antioxidative status of laying hens and improve their production performance and egg quality.

Apparent metabolizable and net energy values of corn and soybean meal for broiler breeding cocks.

The AME and net energy (NE) values of 4 corn varieties, including 2 normal corn varieties (Zheng Dan 958 and Xian Yu 335), and one each of waxy corn and sweet corn, and 2 soybean meal samples including regular (RSBM) and dehulled soybean meal (DSBM), were determined in 2 experiments for broiler breeding cocks using the indirect calorimetry method. The 4 test diets in Experiment 1 consisted of each test corn, which replaced 40% of the corn-soybean meal basal diet, and the test diets in Experiment 2 contained 25% RSBM or DSBM, which was used to replace the corn basal diet. Thirty (Experiment 1) or 18 (Experiment 2) 50-week-old Arbor Acre (AA) broiler breeding cocks were used in a completely randomized design. After a 7 d dietary adaptation period, 6 birds as replicates from each treatment were assigned to individual respiration chambers for energy measurement via gaseous exchange and total excreta collection for 10 d. In Experiment 1, the AME, ME intake (MEI), retained energy (RE), NE, and NE:AME ratio values were higher (P < 0.001) in the test diets as compared with the corn-soybean meal basal diet. The AME and NE values in the sweet corn diet were higher (P < 0.05) than those values in the other 3 test diets. The heat production (HP), fasting heat production (FHP), and respiration quotient (RQ) were not influenced by the various experimental diets. The respective AME and NE values were 3,785, 3,775, 3,738, and 3,997 kcal/kg (DM basis), and 2,982, 3,006, 2,959, and 3,146 kcal/kg (DM basis) for Zheng Dan 958, Xian Yu 335, waxy corn, and sweet corn. Birds fed a corn basal diet in Experiment 2 had higher AME, MEI, RE, NE, and NE:AME ratio values (P < 0.001). Soybean meal substitution had no effect on HP, FHP, or RQ. The average AME and NE content was 2,492 and 1,581 kcal/kg (DM basis) for RSBM, and 2,580 and 1,654 kcal/kg (DM basis) for DSBM, respectively.

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis.

Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.

Investigation of the inhibitors of histone-lysine N-methyltransferase SETD2 for acute lymphoblastic leukaemia from traditional Chinese medicine.

Leukaemia is the leading cause of childhood malignancies. Recent research indicates that the SETD2 gene is associated with acute lymphoblastic leukaemia. This study aims to identify potential lead compounds from traditional Chinese medicine (TCM) using virtual screening for SET domain containing 2 (SETD2) protein against acute lymphoblastic leukaemia. Docking simulation was performed to determine potential candidates which obtain suitable docking poses in the binding domain of the SETD2 protein. We also performed molecular dynamics (MD) simulation to investigate the stability of docking poses of SETD2 protein complexes with the top three TCM candidates and a control. According to the results of docking and MD simulation, coniselin and coniferyl ferulate have high binding affinity and stable interactions with the SETD2 protein. Coniselin is isolated from the alcoholic extract of Comiselinum vaginatum Thell. Coniferyl ferulate can be isolated from Angelica sinensis, Poria cocos (Schw.) Wolf, and Notopterygium forbesii. Although S-adenosyl-L-homocysteine has more stable interactions with key residues in the binding domain than coniselin and coniferyl ferulate during MD simulation, the TCM compounds coniselin and coniferyl ferulate are still potential candidates as lead compounds for further study in the drug development process with the SETD2 protein against acute lymphoblastic leukaemia.

Targeting TYRO3 inhibits epithelial-mesenchymal transition and increases drug sensitivity in colon cancer.

Colon cancer is the third leading cause of death from cancer worldwide with less than 10% survival rate at the late stage. Although mutations of certain genes have been implicated in familial colon cancer development, the etiology of the majority of colon cancer remains unknown. Herein, we identified TYRO3 as a potential oncogene. Immunohistochemical staining results demonstrated that levels of TYRO3 were markedly elevated in polyps and colon cancer cells and were negatively correlated with prognosis. Overexpression of TYRO3 enhanced cell motility, invasion, anchorage-independent growth and metastatic ability, while knockdown of TYRO3 impaired all these processes. Results from meta-analysis showed that TYRO3 was associated with epithelial-mesenchymal transition (EMT) signatures. Gain-of-function and loss-of-function experiments demonstrated that expression of SNAI1, the master regulator of EMT, was regulated by TYRO3 and played a major role in mediating TYRO3-induced EMT processes. The murine model also demonstrated that Tyro3 and Snai1 were upregulated in the early stage of colon cancer development. To provide a proof-of-concept that TYRO3 is a druggable target in colon cancer therapy, we raised anti-TYRO3 human antibodies and showed that treatment with the human antibody abolished TYRO3-induced EMT process. More importantly, administration of this anti-TYRO3 antibody increased drug sensitivity in primary cultured colon cancer cells and xenografted mouse tumors. These findings demonstrate that TYRO3 is a novel oncogene and a druggable target in colon cancer.

Serum brain-derived neurotrophic factor levels and psychotic symptoms in heroin dependence.

OBJECTIVES: Psychotic symptoms are commonly observed among heroin users. Low serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the relationship between serum BDNF levels and psychotic symptoms in heroin dependence are lacking. METHOD: A total of 31 heroin-dependent patients who had never experienced psychotic symptoms during heroin consumption and 21 patients with a history of psychotic symptoms were consecutively recruited. We measured by enzyme-linked immunosorbent assay (ELISA) serum BDNF levels during early abstinence. A gender- and age-matched sample of healthy controls was also recruited and underwent measurement of BDNF. RESULTS: BDNF levels were significantly lower in patients with psychotic symptoms than in those without psychotic symptoms (P<0.001). BDNF levels were not found to be correlated with sex, age, age of onset, duration of heroin use, average daily dose of heroin use, frequency of heroin use, SDS scores, BAI scores and BDI scores in the psychotic subsamples (all P>0.05). CONCLUSIONS: Our findings suggest that heroin-dependent patients with psychotic symptoms share some of the neurotrophic insult that characterizes schizophrenia and psychosis.

The oncogenic role of androgen receptors in promoting the growth of oral squamous cell carcinoma cells.

OBJECTIVES: The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. MATERIALS AND METHODS: Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. RESULTS: OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. CONCLUSION: Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.

GSK3ß controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug.

Glycogen synthase kinase 3 beta (GSK3ß) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3ß-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3ß-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3ß-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.

Dose-dependent effects of D-methionine for rescuing noise-induced permanent threshold shift in guinea-pigs.

The purpose of this study was to examine the dose-response effectiveness of d-methionine (d-met) in rescuing a noise-induced permanent threshold shift (PTS) and cochlear biochemistry following noise exposure. One hour after being exposed to continuous broadband white noise at 105dB sound pressure level (SPL) for 6h, guinea-pigs were treated five times at 12-h intervals with 200, 400, or 600mg/kg d-met or sterile 0.9% saline (each group, N=6) by intraperitoneal injection. Six guinea-pigs with normal hearing that were not exposed to noise served as control animals. Although administration of d-met 200mg/kg did not significantly reduce the mean PTS, treatment with d-met 600mg/kg achieved a complete rescue response. The level of rescue from noise-induced PTS following treatment with 200, 400, or 600mg/kg d-met was dose dependent. The attenuation of the noise-induced decreases in the activities of the Na(+), K(+)-ATPase and Ca(2+)-ATPase following treatment with 200, 400, or 600mg/kg d-met was also dose dependent. Likewise, d-met-dose-dependent decreases in mean lipid peroxidation and nitric oxide levels were observed in the d-met treated groups. Significant attenuation of increased oxidative stress and decreased ATPase activities was concurrent with the d-met-mediated improvements in noise-induced auditory dysfunction.