Association of dietary antioxidant intake with depression risk and all-cause mortality in people with prediabetes.

People with diabetes has an elevated risk of depression, and depression contributes to a worse prognosis for people with diabetes. Dietary antioxidants have been shown to reduce the risk of depression in the general population. Therefore, we hypothesized that dietary antioxidants would also help to reduce the risk of depression and all-cause mortality in people with prediabetes. A total of 8789 participants aged 20 years and older from the 2005-2018 National Health and Nutrition Examination Surveys who met the diagnostic criteria for prediabetes were included in our study. The associations between six dietary antioxidant intakes and the composite dietary antioxidant index (CDAI) with depression risk and all-cause mortality were assessed using weighted logistic and Cox regression. Possible nonlinear associations were further explored using restricted cubic spline. To ensure the reliability of the findings, the multiple imputations by chained equation were applied to missing covariates to avoid potential bias. Our study found that moderate dietary antioxidant intake prevents depression and improves prognosis in people with prediabetes. Moreover, a CDAI score near three allows for maximum benefit. Our findings could provide clues for early intervention in people with diabetes.

Effect of a systemic intervention combined with a psychological intervention in stroke patients with oropharyngeal dysfunction.

BACKGROUND: Stroke frequently results in oropharyngeal dysfunction (OD), leading to difficulties in swallowing and eating, as well as triggering negative emotions, malnutrition, and aspiration pneumonia, which can be detrimental to patients. However, routine nursing interventions often fail to address these issues adequately. Systemic and psychological interventions can improve dysphagia symptoms, relieve negative emotions, and improve quality of life. However, there are few clinical reports of systemic interventions combined with psychological interventions for stroke patients with OD. AIM: To explore the effects of combining systemic and psychological interventions in stroke patients with OD. METHODS: This retrospective study included 90 stroke patients with OD, admitted to the Second Affiliated Hospital of Qiqihar Medical College (January 2022-December 2023), who were divided into two groups: regular and coalition. Swallowing function grading (using a water swallow test), swallowing function [using the standardized swallowing assessment (SSA)], negative emotions [using the self-rating anxiety scale (SAS) and self-rating depression scale (SDS)], and quality of life (SWAL-QOL) were compared between groups before and after the intervention; aspiration pneumonia incidence was recorded. RESULTS: Post-intervention, the coalition group had a greater number of patients with grade 1 swallowing function compared to the regular group, while the number of patients with grade 5 swallowing function was lower than that in the regular group (P < 0.05). Post-intervention, the SSA, SAS, and SDS scores of both groups decreased, with a more significant decrease observed in the coalition group (P < 0.05). Additionally, the total SWAL-QOL score in both groups increased, with a more significant increase observed in the coalition group (P < 0.05). During the intervention period, the total incidence of aspiration and aspiration pneumonia in the coalition group was lower than that in the control group (4.44% vs 20.00%; P < 0.05). CONCLUSION: Systemic intervention combined with psychological intervention can improve dysphagia symptoms, alleviate negative emotions, enhance quality of life, and reduce the incidence of aspiration pneumonia in patients with OD.

Eukaryotic initiation factor 3b regulates the development and progression of breast cancer.

The tumorigenesis of breast cancer is a complex process involving multiple factors, among which abnormal gene expression is a key event. Nevertheless, studies on the regulation of gene expression have focused primarily on the transcriptional level, although the abnormal translation regulation is also closely related to tumorigenesis. Accumulating evidence has indicated the dysregulation of eukaryotic initiation factor (eIF) subunits in a variety of tumors, which contributes to the malignant transformation, tumor growth, metastasis, and the prognosis of patients. In this study, we examined the expression of eIF3b and found an upregulation of eIF3b in breast cancer cell lines as well as tumor tissues. In addition, the expression of eIF3b was related to the tumor stage with highest eIF3b expression in TNM stage III-IV and/or lymph node metastatic breast cancer. Furthermore, in vitro experiments demonstrated that eIF3b knockdown markedly inhibited tumor hyperplasia as well as the migration and invasion of breast cancer cells, while eIF3b overexpression showed the opposite effects. Importantly, eIF3b silencing inhibited the growth and pulmonary metastasis of xenograft tumor in breast cancer mouse model. Mechanistically, we found that eIF3b downregulation suppressed the malignant development of breast cancer by modulating Wnt/ß-catenin pathway. Collectively, our data suggested that eIF3b might not only participate in the tumorigenesis of breast cancer, but also promote the proliferation, invasion, and metastasis of tumor cells. Thus, eIF3b may service as a potential therapeutic target for the treatment of patients with breast cancer.

Impact of extended nursing model after multi-disciplinary treatment on young patient with post-stroke.

BACKGROUND: Stroke has become one of the most serious life-threatening diseases due to its high morbidity, disability, recurrence and mortality rates. AIM: To explore the intervention effect of multi-disciplinary treatment (MDT) extended nursing model on negative emotions and quality of life of young patients with post-stroke. METHODS: A total of 60 young stroke patients who were hospitalized in the neurology department of our hospital from January 2020 to December 2021 were selected and randomly divided into a control group and an experimental group, with 30 patients in each group. The control group used the conventional care model and the experimental group used the MDT extended nursing model. After the in-hospital and 3-mo post-discharge interventions, the differences in negative emotions and quality of life scores between the two groups were evaluated and analyzed at the time of admission, at the time of discharge and after discharge, respectively. RESULTS: There are no statistically significant differences in the negative emotions scores between the two groups at admission, while there are statistically significant differences in the negative emotions scores within each group at admission and discharge, at discharge and post-discharge, and at discharge and post-discharge. In addition, the negative emotions scores were all statistically significant at discharge and after discharge when compared between the two groups. There was no statistically significant difference in quality of life scores at the time of admission between the two groups, and the difference between quality of life scores at the time of admission and discharge, at the time of discharge and post-discharge, and at the time of admission and post-discharge for each group of patients was statistically significant. CONCLUSION: The MDT extended nursing mode can improve the negative emotion of patients and improve their quality of life. Therefore, it can be applied in future clinical practice and is worthy of promotion.

Total Barley Maiya Alkaloids Prevent Increased Prolactin Levels Caused by Antipsychotic Drugs and Reduce Dopamine Receptor D2 via Epigenetic Mechanisms.

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people's quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels. Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction. Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3ß) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing. Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs. Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.

Testicular injury during SARS-CoV-2 infection may be neglected: An assessment from scRNA-seq profiling and protein detection of angiotensin-converting enzyme II.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is outbreaking globally. SARS-CoV-2 invades host cells via angiotensin-converting enzyme II (ACE2) and causes multiple-organ injury. Autopsy studies indicated that the testis of patients with COVID-19 exhibited various degrees of spermatogenic cell reduction and injury, but the composition of ACE2-expressing cells and their proportion in the testes have remained to be determined. Recent clinical evidence suggested that the ratio of male sex hormones in males with COVID-19 was significantly changed. The present study aimed to explore whether SARS-CoV-2 is able to damage the male reproductive system. For this, the ACE2-expressing cell composition and proportion in male testes were analyzed using single-cell RNA sequencing (RNA-seq) datasets downloaded from the Gene Expression Omnibus (GEO) database and immunohistochemical (IHC) staining. The single-cell RNA-seq data indicated that ACE2 mRNA was highly expressed in myoid cells, Leydig cells and spermatogenic cells, accounting for 5.45, 1.24 and 0.423% of adult testicular cells. ACE2 mRNA-expressing Sertoli cells, spermatogenic cells and myoid cells accounted for 5.00, 0.56 and 0.73% of infant testicular cells. IHC demonstrated that ACE2 protein was also highly expressed in testicular tissues. In conclusion, the present results demonstrated that testicular injury may be missed by clinicians in patients with COVID-19 and male reproductive function should be closely followed up.

Bay-Region Annulative π-Extension of o-Iodobiphenyls with Aliphatic Anhydrides Catalyzed by Pd(OAc)2.

Bay-region annulative π-extension of o-iodobiphenyls with aliphatic anhydrides was developed. Many o-iodobiphenyls and aliphatic anhydrides can react well under the optimized conditions. A lot of phenanthrol derivatives can be efficiently prepared by this approach. The control experiments support that dibenzopalladacyclopentadienes may be the reaction intermediates.

Synthesis of Tribenzo[b,d,f]azepines via Palladium-Catalyzed Annulation Reaction of 2-Iodobiphenyls with 2-Halogenoanilines.

A palladium-catalyzed annulation reaction of 2-iodobiphenyls with 2-halogenoanilines has been developed. A variety of 2-iodobiphenyls and 2-halogenoanilines can undergo this transformation. Diversified tribenzo[b,d,f]azepine derivatives can be synthesized in moderate to excellent yields according to this method.

ω-3PUFAs Improve Cognitive Impairments Through Ser133 Phosphorylation of CREB Upregulating BDNF/TrkB Signal in Schizophrenia.

Schizophrenia (SZ) is a serious mental condition and is associated with cognitive impairments. Brain-derived neurotrophic factor (BDNF) is one of the learning- and memory-related molecules found in the CNS and its level was reported to be reduced in SZ brain, while ω-3 polyunsaturated fatty acids (ω-3PUFAs) could improve SZ symptoms, but its mechanism of action remains unknown. Using MK801 injection-induced SZ rat model, we here found that supplementation with ω-3PUFAs improved the levels of p-CREB, BDNF, and p-TrkB in the brain of SZ rats, and restore hippocampal neuronal damage, thereby reducing cognitive impairments in SZ rats. However, overexpression of AAV9/CREB S133A (CREB inactivated mutation) downregulated BDNF/TrkB signaling pathway and remarkably abolished the preventive effect of ω-3PUFAs in MK801-induced schizophrenia. Interestingly, AAV9/CREB S133D (CREB activated mutation) improved synaptic dysfunctions and cognitive defects in MK801 rats. In conclusion, these findings indicate that MK801-induced SZ lesions dephosphorylate CREB at Ser133 site, leading to neuron damage, and ω-3PUFAs improve SZ cognitive impairments by upregulating the CREB/BDNF/TrkB pathway, which provides new clues for the mechanism of SZ cognitive impairments, and a basis for therapeutic intervention.

hsa_circ_0006459 and hsa_circ_0015962 affect prognosis of Dengue fever.

Circular ribonucleic acids (circRNAs) are widely expressed in human cells and play an important role in the pathogenesis of many diseases. Some circRNAs have microRNA (miRNA) binding response elements and interact with miRNA to regulate the expression of target genes.Four patients with a preliminary diagnosis of dengue fever (DF), peripheral whole blood sample in anticoagulant was collected before treatment (pretreatment group) and after effective treatment (posttreatment group), and eight samples were separated and used to screen differentially expressed circRNAs with microarray analysis. The relative expression level of circRNAs was determined using reverse-transcription polymerase chain reaction (RT-PCR). TargetScan v7.1 and miRDB v5 bioinformatics software were used to predict circRNA-binding miRNAs; dual luciferase reporters were constructed to detect binding between circRNA and miRNA. Microarray screening revealed 263 differentially expressed circRNAs in peripheral leukocytes pretreatment versus posttreatment; 107 of these were upregulated and 156 were downregulated. RT-PCR confirmed that hsa_circ_0015962 was significantly upregulated and hsa_circ_0006459 significantly downregulated (P < 0.05). Moreover, hsa_circ_0015962 binds to miR-4683, and hsa_circ_0006459 binds to miR-133b.Downregulation of hsa_circ_0006459 and upregulation of hsa_circ_0015962 affect the treatment response of DF and are potential biomarkers in DF patients. The molecular mechanism involves hsa_circ_0006459-mediated targeted negative regulation of miR-133b and hsa_circ_0015962-mediated targeted negative regulation of miR-4683.

Jumonji domain containing 5 is a potential prognostic indicator in non-small cell lung cancer patients who received platinum-based chemotherapy.

BACKGROUND: Platinum-based chemotherapy is the cornerstone of non-small cell lung cancer (NSCLC) therapy. However, the molecular mechanisms and predictive markers of platinum chemoresistance have not been fully understood. Our recent study revealed that Jumonji domain containing 5 (JMJD5) expression in cells was elevated under DNA damage by alkylating agent or UV radiation, which suggests a potential role of JMJD5 in DNA damage related chemoresistance. However, the role of JMJD5 in NSCLC chemotherapy has not been reported. In this study, we demonstrated JMJD5 as a potential prognostic indicator in NSCLC patients who received platinum-based chemotherapy. METHODS: JMJD5 protein expression level in tumor and adjacent normal tissues were detected by immunohistochemistry. Samples were from primary NSCLC patients who received platinum-based chemotherapy after surgical resection. Survival curves were presented by the Kaplan-Meier method and p value was acquired by log-rank test. Multivariate analysis was tested by Cox proportional-hazards regression method. RESULTS: Elevated JMJD5 expression was found in 27.2% cases of tumor tissues (22/81), and high JMJD5 expression were significantly associated with poor overall survival time (OS) [HR =2.881 (1.774-9.121), P=0.001] and progression-free survival time (PFS) [HR =2.255 (1.417-5.886), P=0.004] in NSCLC patients who received platinum-based chemotherapy. In multivariate analyses, JMJD5 was proved to be an independent prognostic indictor for shorter OS [HR =2.339 (1.158-4.724), P=0.018] and PFS [HR =2.031 (1.095-3.767), P=0.025). CONCLUSIONS: High JMJD5 expression indicated a worse prognosis in NSCLC patients who received platinum-based chemotherapy, and JMJD5 may serve as a novel predictive marker in NSCLC chemotherapy.

miR-21 is involved in transforming growth factor ß1-induced chemoresistance and invasion by targeting PTEN in breast cancer.

Transforming growth factor ß1 (TGF-ß1) has been associated with poor outcomes in patients with breast cancer. However, the functions and underlying molecular mechanisms of TGF-ß1 in breast cancer remain unknown. Therefore, the present study aimed to identify the effects of components of the TGF-ß/microRNA (miR-)21/phosphatase and tensin homolog (PTEN) signaling axis in breast cancer. TGF-ß1 was identified to upregulate the expression of miR-21, and miR-21 was demonstrated to be significantly upregulated in breast cancer tissues compared with benign proliferative breast disease. In addition, the expression of miR-21 was significantly associated with increased TGF-ß1 and clinical characteristics in patients, including tumor grade and lymph node metastasis (all P<0.05). Furthermore, in the breast cancer MCF-7 cell line, TGF-ß1 was revealed to induce the expression of miR-21 in a dose- and time-dependent manner. The results of the present study additionally demonstrated that increased miR-21, in response to TGF-ß1 signaling, was associated with tumor invasion and chemoresistance in vitro. In addition, suppression of PTEN was mediated by TGF-ß1-induced expression of miR-21 in breast cancer cells and using a miR-21 inhibitor revitalized the expression of PTEN. The results of the present study explored the functions of TGF-ß1-stimulated expression of miR-21 to suppress the PTEN axis, which promotes breast cancer progression and chemoresistance.

ω-3PUFAs prevent MK-801-induced cognitive impairment in schizophrenic rats via the CREB/BDNF/TrkB pathway.

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids (ω-3PUFAs) on MK-801-induced cognitive impairment in schizophrenia (SZ) rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.

Identification of a Fused-Ring 2'-Deoxyadenosine Adduct Formed in Human Cells Incubated with 1-Chloro-3-buten-2-one, a Potential Reactive Metabolite of 1,3-Butadiene.

1-Chloro-3-buten-2-one (CBO) is an in vitro metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO exhibited potent cytotoxicity and genotoxicity that have been attributed in part to its reactivity toward DNA. Previously, we have characterized the CBO adducts with 2'-deoxycytidine and 2'-deoxyguanosine. In the present study, we report on the reaction of CBO with 2'-deoxyadenosine (dA) under in vitro physiological conditions (pH 7.4, 37 °C). We used the synthesized standards and their decomposition and acid-hydrolysis products to characterize the CBO-DNA adducts formed in human cells. The fused-ring dA adducts (dA-1 and dA-2) were readily synthesized and were structurally characterized as 1,N(6)-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine and 1,N(6)-(1-hydroxy-1-chloromethylpropan-1,3-diyl)-2'-deoxyadenosine, respectively. dA-1 exhibited a half-life of 16.0 ± 0.7 h and decomposed to dA at pH 7.4 and 37 °C. At similar conditions, dA-2 decomposed to dA-1 and dA, and had a half-life of 0.9 ± 0.1 h. These results provide strong evidence for dA-1 being a degradation product of dA-2. dA-1 is formed by replacement of the chlorine atom of dA-2 by a hydroxyl group. The slow decomposition of dA-1 to dA, along with the detection of hydroxymethyl vinyl ketone (HMVK) as another degradation product, suggested equilibrium between dA-1 and a ring-opened carbonyl-containing intermediate that undergoes a retro-Michael reaction to yield dA and HMVK. Acid hydrolysis of dA-1 and dA-2 yielded the corresponding deribosylated products A-1D and A-2D, respectively. In the acid-hydrolyzed reaction mixture of CBO with calf thymus DNA, both A-1D and A-2D could be detected; however, the amount of A-2D was significantly larger than that of A-1D. Interestingly, only A-2D could be detected by LC-MS analysis of acid-hydrolyzed DNA from cells incubated with CBO, suggesting that dA-2 was stable in DNA and thus may play an important role in the genotoxicity and carcinogenicity of BD. In addition, A-2D could be developed as a biomarker of CBO formation in human cells.

Zinc supplement modulates oxidative stress and antioxidant values in rats with severe acute pancreatitis.

Oxidative stress is a main factor in the pathogenesis of severe acute pancreatitis (SAP). The ability of zinc (Zn) to retard oxidative processes has been recognized for many years. This study aims to examine the levels of free oxygen radicals and antioxidant enzyme in SAP rats and know the effect of Zn supplementation on free oxygen radicals and antioxidant system in rats with SAP. Forty-five male Wistar rats were divided into three groups-the SAP group (n=15), the Zn-treated group (n=15), and the controlled group (n=15). For the SAP group, sodium taurocholate is injected into the pancreatic duct to induce SAP; for the Zn-treated group, Zn (5 mg/kg) is subcutaneously injected immediately after injection of 5% sodium taurocholate. Firstly, the activity of erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), and the content of plasma malondialdehyde (MDA), which are the toxic products of oxidative stress, is measured. Secondly, the levels of free oxygen radicals in the liver and kidney are detected. The result showed that the activity of GSH-Px and SOD was lower in the SAP group than that in the controlled group, although the content of plasma MDA increased. However, the activity of SOD and GSH-Px in the Zn-treated group was not significantly decreased after comparing with the controlled group; in the mean time, the content of MDA was not significantly increased either. Moreover, the content of free radical in liver and kidney was higher in the SAP group compared with the controlled group, but the content of free radical in the Zn-treated group was not higher than that in the controlled group (p>0.05). All of the above indicated that Zn may recover the activity of free radical-scavenging enzymes and decrease the content of free radical for the SAP group rats. In conclusion, the content of free radical increase may be one of the reasons that SAP rats are injured, and it is possible for Zn to be used to treat SAP through scavenging free radical and increasing the activity of SOD and GSH-Px of erythrocyte.

4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/Akt/mTOR-independent pathway.

Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein (4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma.

The positive correlation between DJ-1 and ß-catenin expression shows prognostic value for patients with glioma.

The relationship between DJ-1 and ß-catenin, and its impact on the prognosis for glioma patients has not been fully understood. This study determined the effect of DJ-1 on ß-catenin and the prognostic significance of this interaction in glioma patients. We collected tumor specimens from 88 glioma patients and determined the expression of DJ-1, ß-catenin and PTEN by using immunohistochemical staining. The involvement of DJ-1 and ß-catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ-1 expression (37.5%) and high ß-catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ-1 (P = 0.014) was a strong independent prognostic factor, correlated with a reduced overall survival time. In vitro DJ-1 expression was positively correlated with the expression levels of ß-catenin and p-Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO-38 and SHG44 human glioma cell lines. After the knockdown of DJ-1, Akt, p-Akt or ß-catenin expression levels were not affected in the PTEN-null cell lines (U87 and U251 MG). However, in the SWO-38 cell line, which has wild-type PTEN protein, the level of PTEN increased while Akt/p-Akt and ß-catenin levels were reduced. Furthermore, ß-catenin staining weakened in SWO-38 cells after DJ-1 levels decreased according to immunocytochemical analysis. In conclusion, DJ-1 and ß-catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ-1 may regulate ß-catenin expression via PTEN and p-Akt.

Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene.

The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene.

Silencing of MGMT with small interference RNA reversed resistance in human BCUN-resistant glioma cell lines.

BACKGROUND: Our previous study had cloned two glioma cell lines SWOZ1 and SWOZ2 isolated from parental glioma cell line SWO38. The 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance of SWOZ1 was higher than that of SWOZ2. Since O6-methylguanine-DNA methyltransferase (MGMT) was thought to be closely related to BCNU resistance in glioma, this study aimed to explore the function of MGMT in glioma resistant to BCNU. METHODS: A BCNU resistant glioma cell line SWOZ2-BCNU was established. The expression of MGMT was detected in SWOZ1, SWOZ2 and SWOZ2-BCNU. Small interferencing RNA targeting MGMT was used to silence the expression of MGMT in resistant cell lines SWOZ1 and SWOZ2-BCNU. The cytotoxicity of BCNU to these cells was measured using the cell counting kit-8 assay. Statistical analysis was carried out by one-way analysis of variance in statistical package SPSS 13.0. RESULTS: The resistance of SWOZ1 and SWOZ2-BCNU against BCNU was 4.9-fold and 5.3-fold higher than that of SWOZ2. The results of quantitative RT-PCR and Western blotting confirmed that MGMT was both significantly increased in SWOZ1 and SWOZ2-BCNU compared to SOWZ2. After transfection with small interferencing RNA targeting MGMT, a decreased level of MGMT mRNA expression in SWOZ1 and SWOZ2-BCNU for more than 75% compared to negative control was found and confirmed by Western blotting. As a result, the resistance against BCNU was reversed for about 50% both in the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU. CONCLUSIONS: Silencing MGMT with specific small interferencing RNA can reverse the BCNU resistant phenotype in these glioma cell lines. MGMT may play an important role both in intrinsic and acquired BCNU-resistance in glioma.

[Study on the extraction of polyphenol from Scindapsus officinalis with ultrasonic wave technology optimized by central composite design-response surface method].

OBJECTIVE: To optimize ultrasonic extraction technology process conditions of polyphenol from Scindapsus officinalis by the response surface method. METHODS: Based on ethanol concentration, ultrasonic time, the liquid-solid ratio of single factor experiment, the principle of design for 3 star factor 3 level response surface methodology was applied. With FC extraction method for determination of polyphenols, the response surface optimization extraction conditions were studied. RESULTS: The ethanol concentration of 61.14%, ultrasonic wave extracting time of 59.73 min and the ratio of solvent volume of 27.72:1 (Extract 3 times) were selected as the optimum conditions,the extraction yield of polyphenols was 1.352%, with the theoretical 1.361% for the relative error of -0.66%. CONCLUSION: Ultrasonic extraction is a good method for saving time, energy and material,and can be applied to the polyphenols extraction. Central composite design-response surface optimization can get better ecasting results.