Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

Air quality improvement assessment and exposure risk of Shandong Province in China during 2014 to 2020.

As one of the most polluted provinces in China, air pollution events occur frequently in Shandong. Based on the hourly (or daily) concentrations of six air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO), the situations of air quality improvement in three kinds of cities (key cities, coastal cities and general cities) are assessed comprehensively during 2014-2020. Contrary to the daily maximum 8-h average ozone (MDA8 O3), the annual average concentrations of other pollutants show the downward trends during 2014-2020. Therein, the improvement rates of annual average concentrations of air pollutants in key cities are highest. By 2020, the day proportions of O3 as the primary pollutant are up to 38% in three kinds of cities. Besides, due to the impact of COVID-19, the monthly average concentrations of PM2.5, PM10, NO2, SO2 and CO in February 2020 decrease by 32.1-49.5% year-on-year. There are still about 50% of population exposed to high-risk regions (R i > 2), which are mainly concentrated in main urban areas and industrial areas. Thus, the adjustment of industrial structure and energy composition in the context of carbon peak and carbon neutrality should be implemented in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04651-5.

LncRNA DANCR affected cell growth, EMT and angiogenesis by sponging miR-345-5p through modulating Twist1 in cholangiocarcinoma.

OBJECTIVE: LncRNA DANCR has been reported to play an important role in various cancers. Therefore, this study aimed at exploring the function and regulatory mechanism of DANCR in Cholangiocarcinoma (CCA). PATIENTS AND METHODS: qRT-PCR was used to measure the expression of DANCR, miR-345-5p in tissues and cells. Western blot was applied to measure the protein expression of Twist, N-cadherin, Vimentin, E-cadherin, VEGF-A, VEGF-C, PCNA and C-caspase 3. The relationship between DANCR and miR-345-5p was determined by luciferase reporter assay. MTT assay and flow cytometry were used to assess cell proliferation and apoptosis, respectively. Transwell assay was performed to detect cell invasion and migration. RESULTS: We found that the expression of DANCR was significantly induced in CCA tissues and cells. Inhibition of DANCR remarkably suppressed CCA cell proliferation, migration, invasion, EMT and angiogenesis as well as induced cell apoptosis in vitro and in vivo. Luciferase reporter assay determined that DANCR directly targeted miR-345-5p and Twist1 was a target mRNA of miR-345-5p. Otherwise, miR-345-5p down-expression partially reversed the effect induced by the suppression of DANCR in CCA. Moreover, the suppressive effects of high miR-345-5p expression on CCA cells were reversed by improving Twist1 expression. CONCLUSIONS: In this study, we verified that LncRNA DANCR affected cell proliferation, migration, invasion, angiogenesis, epithelial-mesenchymal transition (EMT) and induced apoptosis through modulating miR-345-5p/Twist1 axis in Cholangiocarcinoma.

MicroRNA-524-5p suppresses cell proliferation and promotes cell apoptosis in gastric cancer by regulating CASP3.

OBJECTIVE: To investigate miR-524-5p expression in gastric cancer (GC) tissues and the regulatory mechanism of miR-524-5p on biological behaviors of GC cell lines, such as proliferation, cell apoptosis and cycle. MATERIALS AND METHODS: The expression of miR-524-5p was detected in 48 paired of GC tissue samples and matched adjacent tissues, and also detected in GC cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Using miR-524-5p mimics, we analyzed the effects of overexpressed miR-524-5p on cell proliferation, cell apoptosis and cycle. Bioinformatics analysis, dual-luciferase activity assay and Western blot were recruited to validate the potential target gene of miR-524-5p. RESULTS: The expression of miR-524-5p was significantly decreased in GC tissue samples and cell lines. Increased miR-524-5p in GC cells significantly decreased cell proliferation capacity, promoted cell apoptosis and induced cell cycle arrest at G0/G1 phase, while decreased miR-524-5p exerted the opposite effects. Dual-luciferase, qRT-PCR and Western blot confirmed CASP3 as a target gene of miR-524-5p. Furthermore, recovery of CASP3 expression attenuated the suppressive effect of miR-524-5p on cell growth. CONCLUSIONS: MiR-524-5p participates in the development of GC via regulating CASP3, which might provide a new prospect for GC diagnosis and therapy.

[Relationship between C-C chemokine receptor type 2 and P38 mitogen-activated protein kinase signaling pathway in the spinal cord of rats with bone cancer pain].

Objective: To investigate the relationship between C-C chemokine receptor type 2(CCR2) and P38 mitogen-activated protein kinase (P38MAPK) signaling pathway in the spinal cord of rats and further clarify the mechanism of bone cancer pain (BCP). Methods: A total of 92 healthy female SD rats, of which 60 were subjected to behavioral tests using a ciliary mechanical stimulation needle. SD rats were randomly divided into six groups: sham operation group (group S), bone cancer pain group (group B), sham operation + DMSO solvent group (group SD), bone cancer pain + DMSO solvent group (group BD), sham operation + RS102895 CCR2 inhibitor group (group SR), bone cancer pain + RS102895 CCR2 inhibitor group (group BR), and Von Frey was used in the behavioral test. Another 32 SD rats were randomly divided into the following 8 groups (n=4): sham operation group (group S), bone cancer pain 5 d group (group B5), bone cancer pain 9 d group (group B9), bone cancer pain 14 d group (group B14), bone cancer pain + DMSO solvent group (group BD), bone cancer pain + RS102895 CCR2 inhibitor 0.5 h group (group BR0.5 h), bone cancer pain + RS102895 CCR2 inhibitor 4 h group (group BR4 h), bone cancer pain + RS102895 CCR2 inhibitor 12 h group (group BR12 h). Western blot was used to detect the expression of P38, p-P38 and CCR2 in spinal cord of rats. Results: At day 5, 7, 9, 14, 21 post-injection, mechanical withdrawal thresholds of group S were(30.9±1.5), (31.9±1.2), (32.0±1.1), (31.6±1.5), (32.2±1.4)g respectively, the mechanical withdrawal thresholds of group B were( 26.4±0.7), (24.4±0.8), (21.4±0.8), (13.5±0.4), (9.9±0.2)g respectively, the mechanical withdrawal thresholds in group B decreased obviously versus group S, and the differences were statistically significant(t=-13.177, -16.660, -23.778, -35.574, -48.401, all P<0.01). At day 9 post-injection, the mechanical withdrawal thresholds in SD, BD, SR and BR groups were (32.4±1.7), (19.4±1.1), (32.1±1.3), (26.3±1.0) g respectively, the difference was statistically significant (F=224.681, P<0.01), and the mechanical withdrawal thresholds in group BD decreased obviously versus group SD, while the mechanical withdrawal thresholds in group BR increased obviously versus group BD. The expression levels of p-P38 in spinal cord of group S, group B5, group B9 and group B14 were(0.08±0.03), (0.20±0.05), (0.40±0.17), (0.65±0.14)respectively, the expression levels of CCR2 were(0.08±0.04), (0.18±0.05), (0.30±0.09), (0.58±0.07)respectively, the difference was statistically significant(F=19.123, 40.746, all P<0.01), and the expression of p-P38 and CCR2 in group B9 were showed a significant up-regulation versus group S. The expression levels of p-P38 in spinal cord of group BD, group BR0.5 h, group BR4 h and group BR12 h were (0.57±0.06), (0.17±0.11), (0.03±0.01), (0.25±0.11)respectively, and the difference was statistically significant(F=29.582, P<0.01). The expression of p-P38 in group BR0.5 h, BR4 h, BR12 h showed a significant down-regulation versus group BD. Conclusion: CCR2 in the spinal cord may be involved in the development of bone cancer pain by activating P38MAPK signaling pathway in rats.

[Prevention and treatment of Horner syndrome in treatment of head and face hyperhidrosis by thoracic sympathetic nerve modulation].

Objective: By summarize the Prevention and Treatment of Horner Syndrome of CT-guided thoracic sympathetic nerve modulation in the treatment of head and face Hyperhidrosis, reduce the occurrence of the complications. Methods: A retrospective analysis was made on 116 patients of CT-guided thoracic sympathetic nerve modulation in the treatment of head and face Hyperhidrosis in The First Hospital of Jiaxing from January 2010 to December 2016. Analysis the reasons of Horner syndrome and external management to sum up the corresponding prevention and treatment measures. Results: Under the guidance of CT positioning, 116 patients were successfully punctured to the intended target (both sides of the R3 above the rib head), after injection of local anesthetic plus contrast agent, CT scan showed there are 39 sides of the liquid parallel to the outside of pleural (26 sides) or over (13 sides) R1 above the rib head. CT scan again after the injection of anhydrous alcohol, there are 43 sides of the liquid parallel to the outside of pleural (24 sides) or over (19 sides) R1above the rib head.After the operation, 22 sides appeared Horner syndrome, 19 of which immediately give physiological saline 5 ml into the ipsilateral Satellite ganglion.Within 2 hours Horner's syndrome completely disappeared, while 3 cases were not treated, Horner syndrome lasts for 3 months to 2 years. Conclusion: The incidence of Horner syndrome relatively high during the CT-guided thoracic sympathetic nerve modulation to treatment of head and face Hyperhidrosis. Injecting 5 ml physiological saline into the ipsilateral Satellite ganglion immediately can completely eliminate this common complications.

[Detection trend of vaginal intraepithelial neoplasia diagnosed by colposcopy guided biopsy from 2013 to 2015].

Objective: To explore the detection trend of vaginal intraepithelial neoplasia (VaIN) of lower genital tract from 2013 to 2015. Methods: A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results: (1) Overall data of CIN, VaIN and VIN: a total of 16 732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16 732/72 128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48% (14 053/72 128), 2.67% (1 923/72 128), 1.05% (756/72 128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99% (14 053/16 732), 11.49% (1 923/16 732), 4.52% (756/16 732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3 955/4 598),83.25%(4 795/5 760) and 83.20% (5 303/6 374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09%(372/4 598), 12.45%(717/5 760) and 13.08%(834/6 374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89%(271/4 598), 4.31%(248/5 760) and 3.72%(237/6 374), respectively. Conclusion: The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

[Efficacy and safety of linezolid among patients with methicillin-resistant Staphylococcus aureus bacteremia].

Objective: To study the efficacy and safety of linezolid for the treatment of patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Totally 52 cases of MRSA bacteremia patients, from January 2010 to April 2014 in the First Affiliated Hospital, School of Medicine, Zhejiang University, were retrospectively analyzed. They were classified into two groups based on linezolid therapeutic regimen: primary treatment with linezolid (19 cases) and alternated to linezolid (33 cases). The following data were collected and compared: clinical characteristics, lasting time of fever, bacterial clearance rate, clinical efficacy, fatality rate, and adverse events. Results: Forty three of the 52 patients (82.7%) suffered complicated MRSA bacteremia. The most common clinical feature was fever[86.5%(45/52)]. Linezolid was initiatively used mostly because of renal insufficiency[68.4%(13/19)]. In the other 33 patient, glycopeptides were initiatively used, then alternated to linezolid because of persistent fever[69.7%(23/33)]; damage of kidney function during treatment period of glycopeptides[12.1%(4/33)]; occurrence of new infectious site related to MRSA[18.2%(6/33)]. The clinical efficacy were 78.9%(15/19) in the group of primary treatment with linezolid and 81.8% (27/33) in the group of alternated to linezolid, persistent time of fever were 4(3, 15) d and 12(5, 24) d, mortality during 28 d period were 15.8% (3/19) and 9.1% (3/33), adverse rate were 15.8% (3/19) and 12.1% (4/33) in these two groups, respectively (all P>0.05). Conclusion: Linezolid is an option with high clinical efficacy and good safety for MRSA bacteremia patients.

Effects of LeY glycan expression on embryo implantation.

OBJECTIVE: To investigate the correlation between LeY glycan expression and embryo implantation. MATERIALS AND METHODS: Uterine epithelial cells before implantation were transfected with FUT1siRNA to inhibit FUT1 (the gene encoding the key enzyme of LeY synthesis) expression and treated with 10 ng/ml leukemia inhibitory factor (LIF). Murine embryo implantation model in vitro was prepared by late blastocysts with identical morphology and treated uterine epithelial cells co-culture. Using RT-PCR, dot blot and observation of embryo attachment to analyze FUT1 gene expression and LeY synthesis of uterine epithelial cells and studied further the correlation of LeY expression level and embryo implantation. RESULTS: FUT1 gene expression and LeY synthesis declined after cells were transfected with FUT1siRNA, and LIF promoted FUT1 expression and LeY synthesis. After expression of FUT1 gene was inhibited, attachment rate of embryos lowered, but LIF up-regulated FUT1 expression and increased the attachment rate of embryos. CONCLUSIONS: These results indicated regulating FUT1 expression affected LeY synthesis, and then LeY regulated the recognition and attachment of uterus-embryo and participates in embryo implantation further.

Propagation of dysbindin-1B aggregates: exosome-mediated transmission of neurotoxic deposits.

Given the detection of aggregated deposits in chronic mental diseases (CMD), the disturbance of proteostasis in those diseases is receiving increasing attention. The study of aggregated proteins can contribute to our understanding of the chronic and progressive condition of such diseases. Dysbindin, encoded by the schizophrenia susceptibility gene DTNBP1, has been reported to co-aggregate with DISC1. However, there has been no evidence to date on the aggregation tendency of dysbindin. Therefore, we investigated the isoform-specific aggregation of dysbindin. We found that dysbindin-1B aggregated into cell-invasive deposits in mice. Because of the efficient propagation of dysbindin-1B, we further studied the mechanism of propagation and identified it as exosome-mediated transmission of the aggregates. In addition, aggregates of dysbindin-1B were toxic. Through exosome-mediated propagation, the deposits of dysbindin-1B exerted toxic effects on recipient neurons a long distance away from the initial aggregation site in mice brain. The rapid long distance propagation of neurotoxic deposits of dysbindin-1B in affected neuronal circuitry indicates a possible mechanism for the progressive deterioration of neurons and cognitive function in CMD.

The TNFAIP3 polymorphism rs610604 both associates with the risk of psoriasis vulgaris and affects the clinical severity.

BACKGROUND: Genome-wide association studies in white and Chinese Han populations have found that the single-nucleotide polymorphism (SNP) rs610604, at the tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) locus, is associated with psoriasis, and is also associated with response to TNF blockade in psoriasis. AIM: To examine whether this SNP is also associated with the clinical traits of psoriasis vulgaris (PV). METHODS: A hospital-based case-control study was performed, which involved 647 subjects [351 patients with PV and 296 healthy controls (HC)]. The rs610604 variants were typed using a SNaPshot assay. RESULTS: Both the G allele and the dominant model genotype (GG + GT) of rs610604 were associated with risk of PV (OR = 1.53; P = 0.01 and OR = 1.68, P < 0.01, respectively). In genotype-phenotype analysis, both the G allele and the GG + GT genotype were also associated with the clinical severity of PV. Severe cases [Psoriasis Area and Severity Index (PASI) > 6] had a higher frequency of the G allele and the GG + GT genotype compared with mild cases (PASI ≤ 6) (OR = 2.03, P = 0.001 and OR = 2.46, P < 0.001, respectively). In addition, rs610604 was significantly associated with almost all of the phenotypes in subphenotype-control analyses. CONCLUSIONS: SNP rs610604 in the TNFAIP3 locus is associated with the clinical severity of PV in a Chinese Han population.

Case report. Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa (DEB). This disease is characterized by severe itching, lichenoid nodules or prurigo-like lesions, and linear scarring with a predilection for the extensor limbs. Pathogenic mutations in the type VII collagen alpha 1 (COL7A1) gene have been identified. We analyzed mutations in the COL7A1 gene in a Chinese family including 5 affected individuals with typical DEB-Pr and in a patient previously reported with sporadic DEB-Pr. The entire coding region and exon-intron boundaries of COL7A1 were detected by polymerase chain reaction and direct sequencing. We identified one novel heterozygote mutation (c.6842G>T, p.G2281V) and a second mutation (c.5443G>A, p.G1815R) reported previously in patients with DEB. Our findings contribute to the COL7A1 mutation database and further reveal the genetic and phenotypic heterogeneity of DEB-Pr.

A novel insertion mutation in the ADAR1 gene of a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules that are mainly present on the dorsal portions of the extremities. The DSH locus was mapped to chromosome 1q11-q12 and, subsequently, pathogenic mutations in the double-stranded RNA-specific adenosine deaminase (ADAR1) gene were identified. We performed a mutational analysis of the ADAR1 gene in a Chinese family that included three individuals affected with typical DSH phenotypes. Mutations within the entire coding region and the exon-intron boundaries of ADAR1 were detected and confirmed by polymerase chain reaction and direct sequencing, respectively. An insertion mutation within exon 12, c.3035_3036insC (p.P1012fsX1017), was identified in all family members affected by DSH, but not in the healthy members or 100 unrelated controls. This finding improves our understanding of the role of ADAR1 in DSH.

Leptin levels in patients with psoriasis: a meta-analysis.

BACKGROUND: There have been inconsistent results reported for leptin levels in patients with psoriasis. AIM: To evaluate leptin levels in patients with psoriasis using a meta-analysis of studies comparing leptin levels in controls and in patients with psoriasis. METHODS: PubMed (MEDLINE), EMBASE and the Cochrane Library were searched for relevant papers published in English. Pooled weighted mean differences (WMDs) and 95% CIs were calculated using random-effects and fixed-effects models. Heterogeneity between studies was assessed using the Cochran Q and I(2) statistics. RESULTS: In total, 11 studies, comprising 773 patients with psoriasis and 570 healthy controls, were identified. Leptin levels were significantly higher in patients with psoriasis compared with controls (WMD = 7.24, 95% CI 4.55-9.93; P < 0.001). On stratified analysis, significant differences in leptin levels between patients with psoriasis and controls were reported only in serum samples (P < 0.001), and not in plasma samples (P = 0.025). Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. CONCLUSIONS: Leptin levels are higher in patients with psoriasis compared with those in controls. Future studies are warranted to clarify the association between leptin levels and the pathomechanism of psoriasis.

Application of (15)N- (18)O double stable isotope tracer technique in an agricultural nonpoint polluted river of the Yangtze Delta Region.

One strategy to combat nitrate (NO3-N) contamination in rivers is to understand its sources. NO3-N sources in the East Tiaoxi River of the Yangtze Delta Region were investigated by applying a (15)N-(18)O dual isotope approach. Water samples were collected from the main channel and from the tributaries. Results show that high total N and NO3-N are present in both the main channel and the major tributaries, and NO3-N was one of the most important N forms in water. Analysis of isotopic compositions (δ (18)O, δD) of water suggests that the river water mainly originated from three tributaries during the sampling period. There was a wide range of δ (15)N-NO3 (-1.4 to 12.4 ‰) and a narrow range of δ (18)O-NO3 (3.7 to 9.0 ‰) in the main channel waters. The δ (15)N and δ (18)O-NO3 values in the upper, middle, and lower channels along the river were shifted as 8.2, 3.5, and 9.5 ‰, and 9.0, 4.2, and 6.0 ‰, respectively. In the tributary South Tiao, the δ (15)N and δ (18)O-NO3 values were as high as 9.5 and 7.0 ‰, while in the tributaries Mid Tiao and North Tiao, NO3-N in most of the samples had relatively low δ (15)N and δ (18)O-NO3 values from 2.3 to 7.5 ‰ and 4.7 to 7.0 ‰, separately. Our results also suggest that the dual isotope approach can help us develop the best management practice for relieving NO3-N pollution in the rivers at the tributary scale.

Study of the physicochemical properties and oral bioavailability of the solid dispersion of cantharidin with polyethylene glycol 4000.

Cantharidin (CA) is partially water-soluble. Solid dispersion of CA (CA-SD) in polyethylene glycol 4000 (PEG 4000) was carried out by a solvent-fusion method to increase its dissolution rate and oral bioavailability. The physicochemical properties of this solid dispersion (SD) were evaluated immediately after preparation by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), and the oral in vivo bioavailability was studied. In in vitro experiments CA was analyzed by high-pressure liquid chromatography (HPLC) and by gas chromatography-mass spectrometry (GC-MS) in in vivo experiments. The solubility and dissolution rate of CA were improved by the SD technique. A comparison of the pharmacokinetics between CA-SD and free CA was performed in rats. The results showed that CA-SD had a higher bioavailability than free CA after oral dosing. By comparing the AUC(0-t) of CA and CA-SD, the relative bioavailability of CA-SD to free CA was 295.4%. From these observations it could be concluded that the CA-SD has a higher absorption than pure CA and this corresponds with the dissolution result in vitro.

Influence of propylthiouracil and methimazole pre-treatment on the outcome of iodine-131 therapy in hyperthyroid patients with Graves' disease.

There is ongoing controversy about potential differences in the influence of the anti-thyroid drugs propylthiouracil (PTU) and methimazole (MMI) on radioiodine treatment of Graves' hyperthyroidism. This retrospective study investigated the influence of PTU and MMI pre-treatment, individually or sequentially, on the outcome of iodine-131 ((131)I) therapy in 199 patients with Graves' disease who had been treated with (131)I for the first time and followed up at 3 and 6 months after treatment. Pre-treatment with PTU, or sequential PTU and MMI pre-treatment, increased the failure rate of (131)I therapy and reduced the rate of hypothyroidism. MMI pre-treatment alone had no significant influence on the results of (131)I therapy. Logistic regression analyses indicated that PTU pre-treatment and having a thyroid gland of > 60 g were both significantly related to (131)I therapy failure.

Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc.

Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc.

Effect of chemopreventive compounds from Brassica vegetables on NAD(P)H:quinone reductase and induction of DNA strand breaks in murine hepa1c1c7 cells.

We have compared the effects of aqueous extracts of cooked Brussels sprouts, isolated glucosinolates and their breakdown products on the activity of quinone reductase [NADPH:quinone-reductase] (QR) and on DNA strand breaks induced by hydrogen peroxide in murine hepa1c1c7 cells. QR activity was not significantly altered after incubation of the cells with Brussels sprouts extracts. However, some of the glucosinolates and in particular their myrosinase-catalysed hydrolysis products and the degradation product of indole-glucosinolates, indole-3-carbinole (I3C), di(indol-3-yl)-methane (DIM) and 2,3-bis(indol-3-ylmethyl)indole (TRI) effectively induced QR activity. Isolated isothiocyanates did not influence the QR activity. The extracts of cooked and autolysed Brussels sprouts and some glucosinolates inhibited the DNA strand breaks induced by 100 microM hydrogen peroxide. Maximum inhibition was by 20-38% after 24 h of preincubation. Hydrolysis of the glucosinolates by myrosinase decreased the inhibitory effects, whereas I3C, DIM or TRI had no effect on DNA damage. Accordingly, the protective effect of Brussels sprouts constituents against induction of oxidative DNA damage appears to be unrelated to enzyme inducing properties via the antioxidant responsive element. Both of these effects could be part of the suggested cancer preventive effect of cruciferous vegetables.