Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury.Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway,which may highlight a potential role of WFA for the treatment of ICH.

Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials

Objective:To identify differentially expressed long non-coding RNAs(lncRNAs) involved in the metastasis of epithelial ovarian cancer.Methods:An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines.Total RNA was then extracted,and microarray analysis was performed.Moreover,nine lncRNAs were selected for validation using RT-qPCR.Results:Compared with the SKOV3 cells,the SKOV3.ip1 cells significantly improved in the in vitro invasive activity.Of the 4,956 lncRNAs detected in the microarray,583 and 578 lncRNAs were upregulated and downregulated,respectively,in SKOV3.ip1 cells,compared with the parental SKOV3 cells.Seven of the analyzed lncRNAs(MALAT1,H19,UCA1,CCAT1,LOC645249,LOC100128881,and LOC100292680) confirmed the deregulation found by microarray analysis.Conclusion:LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials.This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis.Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.

CLINICAL APPLICATION OF BODY DIFFUSION WEIGHTED MR IMAGING IN THE DIAGNOSIS AND PREOPERATIVE N STAGING OF CERVICAL CANCER

Objective To evaluate the clinical impact of body diffusion weighted imaging (DWI) on the diagnosis and preoperative N staging of cervical cancer. Methods Twenty-four patients (mean age 37.9 years old) with proved cervical cancer by cervical biopsy and 24 female patients with other suspected pelvic abnormalities received preoperative body DWI scan. Results of body DWI were compared with pathological findings. The apparent diffusion coefficient (ADC) values of normal cervix and different pathological types of cervical cancer were compared. ADC value of normal or inflammatory lymph nodes was also compared with that of metastatic ones. Student's t test was used for statistical analysis. Results There were 5 adenocarcinomas and 19 epitheliomas showed with biopsy results, and DWI showed 21 cervical lesions out of them (87.5%). ADC values of the normal cervix (n = 24), epithelioma (n = 19), and adenocar- cinoma (n = 5) were (1.73 ± 0.31) ×10-3, (0.88 ± 0.22) ×10-3, and (1.08 ± 0.12) ×10-3 mm2/s, respectively. Statistical analysis showed significant difference in ADC value between normal cervical tissue and either tumor tissues (both P < 0.01). In patients had lymphadenectomy (n = 24), totally 67 lymph nodes including 16 metastatic lymph nodes were pathologically analyzed, and DWI showed 66 (98.5%) out of them. ADC values of normal/inflammatory and metastatic lymph nodes were (1.07 ± 0.16) ×10-3 and (0.77 ± 0.13) ×10-3 mm2/s (P < 0.01). Receiver operating characteristic (ROC) curve of ADC value of metastatic lymph node showed that area under curve was 0.961. Conclusions ADC value in cervical carcinoma is lower than that in normal cervix, and ADC may have predictive value in subtype discrimination. ADC value may improve the preoperative characterization of lymph node metastasis. And at least abdominal and pelvic DWI scan is suggested for N staging evaluation in such patients.

Morphological and genomic evidence for a new species of Corallorhiza(Orchidaceae:Epidendroideae)from SW China

Corallorhiza sinensis,a new species of mycoheterotrophic orchid from western Sichuan,China,is described and illustrated based on molecular and morphological evidence.It is morphologically similar to Corallorhiza trifida,but can be distinguished by bigger flowers,both sepals and petals with 3 veins,and longer lateral lobes of lip.To distinguish the new Corallorhiza species and explore its phylogenetic position within subtribe Calypsoinae,this study employed sequences of the nuclear ribosomal DNA(nrDNA)and whole plastome assembled from the genome skimming approach.The plastome is 148,124 bp in length,including a pair of inverted repeats(IRs)of 26,165 bp,a large single-copy region(LSC)of 82,207 bp,and a small single-copy region(SSC)of 13,587 bp.Further,phylogenetic analyses were performed using nrDNA sequence and 79 coding sequences(CDSs)from 26 complete plastomes of subtribe Calypsoinae.The phylogenetic tree based on nrDNA sequence suggested that Corallorhiza is a monophyletic group,and strongly support C.sinensis as sister to the rest species of Corallorhiza.The plastid tree showed that 10 Corallorhiza species grouped into two clades and C.sinensis is most closely related to the North American C.striata and C.bentleyi instead of Oreorchis foliosa and O.angustata in the same clade.The plastid tree and nrDNA tree indicate Oreorchis is a paraphyletic.Although the topological conflicts are displayed between plastome and nrDNA phylogenies of C.sinensis,it is still the most closely related to Corallorhiza.Comparative analysis showed that C.sinensis populations are characteristic of the intermediate morphological traits between Corallorhiza and Oreorchis.The finding of this new species from China shed new light on the phylogeny of Oreorchis and Corallorhiza.

Serum microRNA-204 levels are associated with long-term cardiovascular disease risk based on the Framingham risk score in patients with type 2 diabetes: results from an observational study

Background Previous studies have demonstrated that micro RNA-204(mi R-204) is involved in atherosclerosis and vascular calcification. However, the value of mi R-204 as the predictive biomarker for cardiovascular disease(CVD) remains unclear. We aimed to evaluate the association between the circulating mi R-204 level and ten-year CVD risk based on the Framingham risk score(FRS). Methods In this retrospective study, we enrolled 194 consecutive patients with type 2 diabetes mellitus(T2DM) without CVD in Beijing Anzhen Hospital between January 2015 and September 2016. We used the FRS to evaluate the risk of CVD for each patient. Circulating mi R-204 levels were measured by quantitative real-time polymerase chain reaction. Results Circulating mi R-204 levels were significantly lower in the group of patients(0.49 ± 0.13) at high risk of CVD(FRS > 20%) than in the low(FRS < 10%) and intermediate(FRS: 10%–20%) risk groups(0.87 ± 0.19 and 0.75 ± 0.25, respectively;P < 0.001). FRS was negatively correlated with mi R-204 levels(r =-0.421, P < 0.001). According to multivariate logistic analyses, reduced mi R-204 level was independently associated with an increased risk of CVD after adjusting for conventional risk factors(OR = 0.876, 95% CI: 0.807–0.950, P = 0.001). Receiver-operating characteristic curve analysis showed that the circulating mi R-204 level can predict the high risk of CVD with higher specificity than the traditional risk factor of high systolic blood pressure or the protective factor of high-density lipoprotein cholesterol. Conclusions Our study demonstrated that patients with lower circulating mi R-204 levels were at high risk for CVD. After adjustment for potential confounders, mi R-204 was independently associated with CVD in patients with T2DM.

SEVEN CASES OF EPITHELIAL OVARIAN CARCINOMA WITH BRAIN METASTASIS

Objective To summarize the clinical characteristics,treatment,and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.Methods Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosis-affecting factors.Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66%(7/1055).Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases.All the patients were diagnosed at late stage,6 cases with the International Federation of Gynecology and Obstetrics(FIGO)stage IIIc and 1 with FIGO stage IV.The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7±20.0 months(range,23-73 months).Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases.Fifty-seven percent of patients presented extracranial metastasis.Serum CA125 played a role in monitoring reoccurrence and brain metastases.The average survival time was about 12 months.Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy.Conclusions As a rare condition,brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival.However,brain metastasis indicates bad prognosis which can be improved by combined therapy.

Analysis of 30 patients with persistent or recurrent squamous cell carcinoma of the cervix within one year after concurrent chemoradiotherapy

Objective:To investigate the recurrence sites,risk factors,and prognosis of patients with persistent or recurrent squamous cell carcinoma(SCC)of the cervix within one year after undergoing concurrent chemoradiotherapy(CCRT).Methods:Clinical data of 30 patients with persistent or recurrent SCC of the cervix within one year after CCRT between July 2006 and July 2011 were analyzed retrospectively.These data were compared with those of 35 SCC cases with no signs of recurrence after complete remission.These 35 patients were treated during the same period(between 2006 and 2011)and selected randomly.Results:Among these 30 patients,25 exhibited distant metastases of which 14 were observed within 6 months after CCRT.Univariate analysis showed higher incidence of pelvic or para-aortic lymphadenectasis and SCC-ag>10 ng/mL in the group with persistent or recurrent disease before treatment(P<0.01).Multivariate analysis by logistic regression revealed that the pre-therapeutic pelvic or para-aortic lymph node enlargement and SCC-ag>10 ng/mL were the independent risk factors.Palliative chemotherapy was the main treatment option for patients with persistent or recurrent disease.The 2-year survival rate was 21.7%,and the median survival time was 17 months.Conclusion:Patients with persistent or recurrent SCC of the cervix after CCRT exhibited a high rate of distant metastasis with poor prognosis.The pre-therapeutic pelvic or para-aortic lymph node enlargement and SCC-ag>10 ng/mL were identified as the independent risk factors for persistent or recurrent SCC within 1 year after CCRT.

Facile and Cost-Efficient Synthesis of Photovoltaic Polymers via Direct Arylation Coupling

As the high calibre candidate of lightweight and flexible solar cells,polymer solar cells(PSCs)have made tremendous progress in recent years.However,the active photovoltaic materials in PSCs are mainly synthesized by metal-mediated coupling reaction requiring harsh reaction conditions,multiple-step synthesis,and cumbersome purification,which is not cost-efficient and may bring toxicity concerns.It is not favorable to the production of photovoltaic polymers and PSC devices on a large scale,and therefore unsuitable for the PSCs industrialization.Direct arylation coupling reaction via aromatic C―H bonds activation enables the synthesis of conjugated polymers under mild conditions and simultaneously reduces synthetic steps,difficulty,and toxic reaction byproducts.This review provides an overview of the history of preparing representative photovoltaic polymers utilized in PSCs through direct arylation reactions and discusses the activity and selectivity of C―H bonds in typical building blocks under different reaction conditions.Especially,the impact of direct arylation condition on defect formation and photovoltaic performance of the photovoltaic polymers is addressed and compared with conventional Stille coupling methods.

Regioregular Asymmetric Diketopyrrolopyrrole Copolymers with Good Molecular Ordered Assembly Ability for High-performance Polymer Transistors

Introduction of asymmetric units into conjugated polymers is an important strategy to regulate the photophysical and electronic properties of polymers,as asymmetric units can not only regulate solubility and energy levels,but also molecular stacking and orientation,thus giving much higher optoelectronic properties.However,very few studies have been reported in this field.The semiconducting properties of conjugated polymers could be regulated through regioregularity adjustment.Here,we took the asymmetric thiophene/pyridine side group DPP as core and developed the regioregular monomer T-Py-DPP through three steps:alkyl chain introduction,tin monomer coupling and NBS double bromination.The T-Py-DPP monomer was polymerized into reg-PPy TDPP-2FBT with a head-to-head structure.The regioregularity of T-Py-DPP unit endowed reg-PPy TDPP-2FBT with backbone planarity,self-assembly orientation,network-like morphology and high crystallinity in films,thus the superior bipolar transport properties.The highest hole and electron mobilities of reg-PPy TDPP-2FBT were 0.93 and 0.57 cm^(2)·V^(-1)·s^(-1),respectively,with 40%improvement relative to the regiorandom polymer.