BGP-15 alleviates LPS-induced depression-like behavior by promoting mitophagy.

The high prevalence of major depressive disorder (MDD) frequently imposes severe constraints on psychosocial functioning and detrimentally impacts overall well-being. Despite the growing interest in the hypothesis of mitochondrial dysfunction, the precise mechanistic underpinnings and therapeutic strategies remain unclear and require further investigation. In this study, an MDD model was established in mice using lipopolysaccharide (LPS). Our research findings demonstrated that LPS exposure induced depressive-like behaviors and disrupted mitophagy by diminishing the mitochondrial levels of PINK1/Parkin in the brains of mice. Furthermore, LPS exposure evoked the activation of the NLRP3 inflammasome, accompanied by a notable elevation in the concentrations of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6). Additionally, neuronal apoptosis was stimulated through the JNK/p38 pathway. The administration of BGP-15 effectively nullified the impact of LPS, corresponding to the amelioration of depressive-like phenotypes and restoration of mitophagy, prevention of neuronal injury and inflammation, and suppression of reactive oxygen species (ROS)-mediated NLRP3 inflammasome activation. Furthermore, we elucidated the involvement of mitophagy in BGP-15-attenuated depressive-like behaviors using the inhibitors targeting autophagy (3-MA) and mitophagy (Mdivi-1). Notably, these inhibitors notably counteracted the antidepressant and anti-inflammatory effects exerted by BGP-15. Based on the research findings, it can be inferred that the antidepressant properties of BGP-15 in LPS-induced depressive-like behaviors could potentially be attributed to the involvement of the mitophagy pathway. These findings offer a potential novel therapeutic strategy for managing MDD.

Microplastic pollution differences in freshwater river according to stream order: Insights from spatial distribution, annual load, and ecological assessment.

Microplastic (MP) pollution has become a pressing concern in global freshwater ecosystems because rivers serve as essential channels for the transport of terrestrial debris to the ocean. The current researches mostly focus on the large catchments, but the impact on the small catchments remains underexplored. In this study, we employed Strahler's stream order classification to delineate the catchment structure of the Beijiang River in South China. The distribution pattern of MP contamination and the factors influencing the distribution pattern, were assessed across the streams at different orders. We found that the Beijiang River was moderately polluted compare to other rivers in China, with an average MP abundance of 2.15 ± 1.65 items/L. MP abundance ranged from 3.17 to 1.45 items/L in the streams at different orders, and significantly decreased with increasing stream order (R2 = 0.93). This highlights the key role of small rivers as the channels for the transport of MPs from watersheds to main streams. The high abundance of PP and PE fibers, the high correlation between the stream order and the resin proportion (R2 = 0.89), and the significant correlation between MP abundance and proximity to urban centers (P = 0.02), indicated that MP pollution across the streams at different orders was predominantly influenced by anthropogenic activities, rather than natural environmental factors. By integrating MP data with hydrographic information, the annual MP loads for the streams at Orders 1 to Order 5 were estimated to be 4.63, 39.38, 204.63, 503.06, and 1137.88 tons/yr, respectively. Additionally, an ecological risk assessment indicates that MP pollution led to a low risk in the Beijiang River. Our findings deepen the understanding of MP pollution within freshwater river networks, and emphasize the crucial role of tributary systems in transporting MPs to main river channels.

Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer.

BACKGROUND: RNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, the function and molecular mechanism of RNA m5C modification in tumor drug resistance remain unclear. METHODS: The correlation between RNA m5C methylation, m5C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) and EGFR-TKIs resistance was determined in non-small-cell lung cancer (NSCLC) cell lines and patient samples. The effects of NSUN2 on EGFR-TKIs resistance were investigated by gain- and loss-of-function assays in vitro and in vivo. RNA-sequencing (RNA-seq), RNA bisulfite sequencing (RNA-BisSeq) and m5C methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the target gene of NSUN2 involved in EGFR-TKIs resistance. Furthermore, the regulatory mechanism of NSUN2 modulating the target gene expression was investigated by functional rescue and puromycin incorporation assays. RESULTS: RNA m5C hypermethylation and NSUN2 were significantly correlated with intrinsic resistance to EGFR-TKIs. Overexpression of NSUN2 resulted in gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinib in vitro and in vivo. Integrated RNA-seq and m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential target of aberrant m5C modification. NSUN2 methylated QSOX1 coding sequence region, leading to enhanced QSOX1 translation through m5C reader Y-box binding protein 1 (YBX1). CONCLUSIONS: Our study reveals a critical function of aberrant RNA m5C modification via the NSUN2-YBX1-QSOX1 axis in mediating intrinsic resistance to gefitinib in EGFR-mutant NSCLC.

Predictive Factors for Gleason Score Upgrading in Patients with Prostate Cancer after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP). METHODS: We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied. RESULTS: Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = -0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = -0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable. CONCLUSIONS: Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.

Composite acousto-optical modulation.

We propose a composite acousto-optical modulation (AOM) scheme for wide-band, efficient modulation of CW and pulsed lasers. We show that by adjusting the amplitudes and phases of weakly-driven daughter AOMs, diffraction beyond the Bragg condition can be achieved with exceptional efficiencies. Furthermore, by imaging pairs of AOMs with opposite directions of sound-wave propagation, high contrast switching of output orders can be achieved at the driving radio frequency (rf) limit, thereby enabling efficient bidirectional routing of a synchronized mode-locked laser. Here we demonstrate a simplest example of such scheme with a double-AOM setup for efficient diffraction across an octave of rf bandwidth, and for routing a mode-locked pulse train with up to frep = 400 MHz repetition rate. We discuss extension of the composite scheme toward multi-path routing and time-domain multiplexing, so as to individually shape each pulses of ultrafast lasers for novel quantum control applications.

Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II.

Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy.

The genome of Cleistogenes songorica provides a blueprint for functional dissection of dimorphic flower differentiation and drought adaptability.

Cleistogenes songorica (2n = 4x = 40) is a desert grass with a unique dimorphic flowering mechanism and an ability to survive extreme drought. Little is known about the genetics underlying drought tolerance and its reproductive adaptability. Here, we sequenced and assembled a high-quality chromosome-level C. songorica genome (contig N50 = 21.28 Mb). Complete assemblies of all telomeres, and of ten chromosomes were derived. C. songorica underwent a recent tetraploidization (~19 million years ago) and four major chromosomal rearrangements. Expanded genes were significantly enriched in fatty acid elongation, phenylpropanoid biosynthesis, starch and sucrose metabolism, and circadian rhythm pathways. By comparative transcriptomic analysis we found that conserved drought tolerance related genes were expanded. Transcription of CsMYB genes was associated with differential development of chasmogamous and cleistogamous flowers, as well as drought tolerance. Furthermore, we found that regulation modules encompassing miRNA, transcription factors and target genes are involved in dimorphic flower development, validated by overexpression of CsAP2_9 and its targeted miR172 in rice. Our findings enable further understanding of the mechanisms of drought tolerance and flowering in C. songorica, and provide new insights into the adaptability of native grass species in evolution, along with potential resources for trait improvement in agronomically important species.

Potential Myocardial Protection of 3,4-seco-Lupane Triterpenoids from Acanthopanax sessiliflorus Leaves.

A rich of 3,4-seco-lupane triterpenoids including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA) and chiisanogenin (CSG) were isolated from the ethanol extract of the leaves of Acanthopanax sessiliflorus. On the basis of previous studies, this article focused on four important components of 3,4-seco-lupane triterpenoids in Acanthopanax sessiliflorus leaves and explored their protective effects against aconitine-induced cardiomyocyte injury and their molecular mechanisms. The results showed that pretreatment with 3,4-seco-lupane triterpenoids could effectively increase cell viability, reduce CK-MB and LDH activities, reduce ROS production, maintain calcium concentration balance, and inhibit apoptosis, with divaroside having the best effect. In addition, Western blot results showed that divaroside down-regulated Cleaved caspase-3 and Bax and up-regulated Bcl-2 expression through activating the PI3 K/AKT pathway. However, the LY294002 inhibitor reversed this situation. This suggests that 3,4-seco-lupane triterpenoids may be a new hotspot for potential myocardial protective drugs research.

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update.

Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.

Integrated analysis of co-expression and ceRNA network identifies five lncRNAs as prognostic markers for breast cancer.

Long non-coding RNAs (lncRNAs), which competitively bind miRNAs to regulate target mRNA expression in the competing endogenous RNAs (ceRNAs) network, have attracted increasing attention in breast cancer research. We aim to find more effective therapeutic targets and prognostic markers for breast cancer. LncRNA, mRNA and miRNA expression profiles of breast cancer were downloaded from TCGA database. We screened the top 5000 lncRNAs, top 5000 mRNAs and all miRNAs to perform weighted gene co-expression network analysis. The correlation between modules and clinical information of breast cancer was identified by Pearson's correlation coefficient. Based on the most relevant modules, we constructed a ceRNA network of breast cancer. Additionally, the standard Kaplan-Meier univariate curve analysis was adopted to identify the prognosis of lncRNAs. Ultimately, a total of 23 and 5 modules were generated in the lncRNAs/mRNAs and miRNAs co-expression network, respectively. According to the Green module of lncRNAs/mRNAs and Blue module of miRNAs, our constructed ceRNA network consisted of 52 lncRNAs, 17miRNAs and 79 mRNAs. Through survival analysis, 5 lncRNAs (AL117190.1, COL4A2-AS1, LINC00184, MEG3 and MIR22HG) were identified as crucial prognostic factors for patients with breast cancer. Taken together, we have identified five novel lncRNAs related to prognosis of breast cancer. Our study has contributed to the deeper understanding of the molecular mechanism of breast cancer and provided novel insights into the use of breast cancer drugs and prognosis.

The effect of long noncoding RNAs HOX transcript antisense intergenic RNA single-nucleotide polymorphisms on breast cancer, cervical cancer, and ovarian cancer susceptibility: A meta-analysis.

Recent studies have shown that long noncoding RNAs (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) polymorphisms are associated with cancer susceptibility. The greatest threat to women's health among a variety of cancers is breast cancer (BC), cervical cancer (CC), and ovarian cancer (OC), and the incidence of it is increasing. We performed a meta-analysis to clarify the relationship between lncRNA HOTAIR expression and BC, CC, and OC susceptibility. We thoroughly searched PubMed, Embase, and the Cochrane Library to obtain the relevant literature. We extracted data from case groups and control groups for each single-nucleotide polymorphism (SNP) (rs4759314, rs920778, rs189663, rs12826786, rs7958904, and rs874945) and compared the relationship between alleles, codominance models, dominant and invisible models and BC, CC, and OC susceptibility. Our study included 11 studies with a total of 5322 patients. There was a significant association between the rs4759314 polymorphism of HOTAIR and susceptibility to BC, CC, and OC (codominant model: AG/AA odds ratio [OR] = 1.13 [95% confidence intervals [CI], 1.00-1.29], GG/AA OR = 1.54 [95% CI, 1.06-2.23]; dominant model: GG + AG/AA OR = 1.16 [95% CI, 1.02-1.32]; and recessive model: GG/AA + AG OR = 1.51 [95% CI, 1.05-2.19]). The association between the expression of rs920778 and BC, CC, and OC susceptibility was not clear (alleles T/C: OR = 1.28 [95% CI, 0.87-1.89]; in codominant model: CT/CC OR = 1.10, [95% CI, 0.71-1.71], TT/CC OR = 1.29 [95% CI, 0.59-2.80]; dominant model: TC + TT/CC OR = 1.16, [95% CI, 0.73-1.86]; and recessive model: TT/TC + CC OR = 1.43, [95% CI, 0.83-2.47]). HOTAIR polymorphism rs1899663 was associated with BC, CC, and OC susceptibility to a certain extent, (alleles T/G OR = 0.90 [95% CI, 0.69-1.16]; in the codominant model: GT/GG OR = 0.81 [95% CI, 0.50-1.30], TT/GG OR = 1.04 [95% CI, 0.63-1.72]; dominant model: GT + TT/GG OR = 0.82 [95% CI, 0.52-1.29]; and recessive model: TT/GT + GG OR = 1.21 [95% CI, 0.76-1.94]). The rs12826786, rs7958904, and rs874945 polymorphisms were associated with a certain degree of BC, CC, and OC susceptibility, but they were not statistically significant. HOTAIR rs4759314 increased susceptibility to BC, CC, and OC in some patients; rs029778 and rs1899663 also increased susceptibility to some extent. SNPs rs12826786, rs7958904, and rs874945 did not correlate with an effect on patient susceptibility to BC, CC, and OC.

Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co-expression network.

PURPOSE: Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC. METHODS: Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan-Meier analysis was used to predict prognosis-related target genes to identify prognostic biomarkers. RESULTS: A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis. CONCLUSION: We performed a distinctive correlation analysis of miRNA-mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.

Targeting Thioredoxin Reductase by Ibrutinib Promotes Apoptosis of SMMC-7721 Cells.

Ibrutinib (IBT), the first-in-class inhibitor of Bruton's tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies. Aside from its therapeutic mechanism through BTK inhibition, IBT has other target sites reported for cancer therapy, leading us to investigate whether IBT has unreported targets. Our study revealed that IBT can inhibit SMMC-7721 cells through irreversible inhibition of mammalian thioredoxin reductase enzymes. Further study demonstrated that IBT can cause cellular reactive oxygen species elevation and induce cancer cell apoptosis. The discovery of a new target of IBT sheds light on better understanding its anticancer mechanisms and provides a theoretical foundation for its further use in clinical therapy.

Development and Application of Transposable Element-Based Chromosomal Markers for the St Genome in Triticeae.

The St genome, originating from Pseudoroegneria (Nevski) Á. Löve, plays an important role in Triticeae. In this study, the Pseudoroegneria stipifolia genome (2n = 2x = 14, StSt) was screened to identify sequences that could be used for FISH. A total of 163 effective clones were obtained from the genomic plasmid library which was constructed by DNase I digestion of P. stipifolia nuclear genomic DNA. Analysis of these clones identified 112 with characteristics of transposable elements (TEs), 13 with characteristics of tandem repetitive sequences, 8 with characteristics of mRNA sequences, and 30 unknown sequences. Fluorescent signals were detected for 11 of 41 TE sequences on P. stipifolia chromosomes after in situ hybridization and were divided into 4 types according to signal distribution patterns: over the whole St genome chromosomes, telomere to pericentromeric regions, centromere to pericentromeric regions, and terminal regions. The affinity between St and Y genomes was studied using the 11 TE probes in 3 StStYY species. Five TE probes showed no obvious difference between subgenomes, 2 probes displayed divergence only in 2 StStYY species, and 4 probes exhibited significant differences among 3 StStYY species. These results provide a preliminary understanding of the sequence composition of the St genome and enabled 11 novel TE probes to be developed and applied.

Virtual screening-guided discovery of thioredoxin reductase inhibitors.

The selenoprotein thioredoxin reductase (TXNRD) is a promising therapeutic target for cancer. To discover novel TXNRD inhibitors, a library of α, ß-unsaturated carbonyl compounds were applied in structure-based virtual screening for the selection of hit compounds. Fifteen top-ranked compounds were further validated experimentally, exhibiting potent inhibition of TXNRD and remarkable cytotoxicity to cancer cells. The further binding mode analysis indicated that multiple noncovalent interactions between the inhibitors and the active pocket of TXNRD facilitated the formation of covalent bonds between the Sec498 on TXNRD and the α, ß-unsaturated carbonyl groups on inhibitors. Results from both simulations and experiments demonstrated that Sec498 is the prime interaction site for the inhibition of TXNRD. Taking compound 7 as an example, the inhibition of TXNRD by compounds promoted oxidative stress-mediated apoptosis of cancer cells. Given these findings, novel TXNRD inhibitors may be discovered and introduced to the growing fields of small molecule drugs against TXNRD.

Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial.

BACKGROUND: N-acetylcysteine is a classic mucolytic agent. This study aimed to investigate the efficacy of N-acetylcysteine on reducing the risk of exacerbations in bronchiectasis patients. METHODS: A prospective, randomized, controlled trial was conducted between April 1, 2014 and December 31, 2016 in five general hospitals in Shandong Province, China. Adult bronchiectasis patients with at least two exacerbations in the past year were potentially eligible. Patients were randomly assigned to receive oral N-acetylcysteine (600 mg, twice daily, 12 months) or on-demand treatment. RESULTS: A total of 161 patients were eligible for randomization (81 to the N-acetylcysteine group and 80 to the control group). During the 12-month follow-up, the incidence of exacerbations in the N-acetylcysteine group was significantly lower than that in the control group (1.31 vs. 1.98 exacerbations per patient-year; risk ratio, 0.41; 95% CI, 0.17-0.66; P = 0.0011). The median number of exacerbations in the N-acetylcysteine group was 1 (0.5-2), compared with 2 (1-2) in the control group (U = - 2.95, P = 0.003). A total of 24.7% of the N-acetylcysteine group patients and 11.3% of the control group patients remained exacerbation-free throughout the 12-month follow-up (χ2 = 4.924, P = 0.026). Compared with the control group, the volume of 24-h sputum in the N-acetylcysteine group was significantly reduced (t = - 3.091, P = 0.002). Additionally, the N-acetylcysteine group showed a significant improvement in the quality of life. No severe adverse events were reported in the intervention group. CONCLUSION: The long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients in Shandong Province, China. The results of this study should be verified in a larger randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02088216) (Registered date: March 5, 2014).

Determination of five nucleosides by LC-MS/MS and the application of the method to quantify N6 -methyladenosine level in liver messenger ribonucleic acid of an acetaminophen-induced hepatotoxicity mouse model.

Ribonucleic acid N6 -methyladenosine methylation plays an important role in a variety of biological processes and diseases. Acetaminophen-induced hepatotoxicity is one of the major challenges faced by clinicians. To date, the link between N6 -methyladenosine and acetaminophen-induced hepatotoxicity has not been studied. In this study, a simple ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of five nucleosides (adenosine, uridine, cytidine, guanosine, and N6 -methyladenosine) in messenger ribonucleic acid. After enzymatic digestion of messenger ribonucleic acid, the nucleosides sample was separated on an Acquity UPLC column with gradient elution using methanol and 0.02% formic acid water, and detected by a Qtrap 4500 mass spectrometer with an electrospray ionization mode. The method was validated over the concentration ranges of 4-800 ng/mL for adenosine, uridine, cytidine, and guanosine and 0.1-20 ng/mL for N6 -methyladenosine. It was successfully applied to the determination of N6 -methyladenosine levels in liver messenger ribonucleic acid in an acetaminophen-induced hepatotoxicity mouse model and a control group. This study offers a method for the determination of nucleoside contents in epigenetic studies and constitutes the first step toward the investigation of ribonucleic acid methylation in acetaminophen-induced hepatotoxicity, which will facilitate the elucidation of its mechanism.

Impact of endometriosis on risk of ovarian, endometrial and cervical cancers: a meta-analysis.

PURPOSE: The risks of gynecologic cancer have not been well established in women with endometriosis. The objective of the present study was to investigate the influence of endometriosis on the risk for three gynecologic cancer (ovarian cancer, endometrial cancer and cervical cancer). METHODS: We gathered updated evidence about the risk relationship between endometriosis and gynecologic cancers by conducting a comprehensive search of several medical literature electronic databases, including PubMed, Embase and the Cochrane Library. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS), and a random-effects model was used to calculate pooled risk ratio (RR). RESULTS: Of the 8538 articles our search produced, we selected 25 qualified studies, including 16 cohort studies and 9 case-control studies. Patients with endometriosis had both an increased risk of ovarian cancer [RR 1.964; 95% CI (1.685, 2.290)]. The risk of endometrial cancer (EC) is not necessarily higher in patients with endometriosis [RR 1.176, 95% CI (0.878, 1.575)]. Endometriosis was not associated with an increased risk for cervical cancer (CC) [RR 0.670, 95% CI (0.537, 0.838)]. CONCLUSIONS: Patients with endometriosis need to be closely observed and rechecked regularly to prevent malignant changes.

Xanthatin Promotes Apoptosis via Inhibiting Thioredoxin Reductase and Eliciting Oxidative Stress.

Xanthatin (XT), a naturally occurring sesquiterpene lactone presented in cocklebur ( Xanthium strumarium L.), is under development as a potential anticancer agent. Despite the promising anticancer effect of XT, the molecular mechanism underlying its cellular action has not been well elucidated. The mammalian thioredoxin reductase (TrxR) enzymes, the essential seleno-flavoproteins containing a penultimate selenocysteine (Sec) residue at the C-terminus, represent a promising target for cancer chemotherapeutic agents. In this study, XT inhibits both the purified TrxR and the enzyme in cells. The possible binding mode of XT with the TrxR protein is predicted by the covalent docking method. Mechanism studies reveal that XT targets the Sec residue of TrxR and inhibits the enzyme activity irreversibly. Simultaneously, the inhibition of TrxR by XT promotes the oxidative stress-mediated apoptosis of HeLa cells. Importantly, the knockdown of the enzyme sensitizes the cells to XT treatment. Targeting TrxR thus discloses a novel molecular mechanism in accounting for the cellular action of XT and provides insights into the development of XT as an anticancer agent.

Karyotypic evolution of the Medicago complex: sativa-caerulea-falcata inferred from comparative cytogenetic analysis.

BACKGROUND: Polyploidy plays an important role in the adaptation and speciation of plants. The alteration of karyotype is a significant event during polyploidy formation. The Medicago sativa complex includes both diploid (2n = 2× = 16) and tetraploid (2n = 2× = 32) subspecies. The tetraploid M. ssp. sativa was regarded as having a simple autopolyploid origin from diploid ssp. caerulea, whereas the autopolyploid origin of tetraploid ssp. falcata from diploid form ssp. falcata is still in doubt. In this study, detailed comparative cytogenetic analysis between diploid to tetraploid species, as well as genomic affinity across different species in the M. sativa complex, were conducted based on comparative mapping of 11 repeated DNA sequences and two rDNA sequences by a fluorescence in situ hybridization (FISH) technique. RESULTS: FISH patterns of the repeats in diploid subspecies caerulea were highly similar to those in tetraploid subspecies sativa. Distinctly different FISH patterns were first observed in diploid ssp. falcata, with only centromeric hybridizations using centromeric and multiple region repeats and a few subtelomeric hybridizations using subtelomeric repeats. Tetraploid subspecies falcata was unexpectedly found to possess a highly variable karyotype, which agreed with neither diploid ssp. falcata nor ssp. sativa. Reconstruction of chromosome-doubling process of diploid ssp. caerulea showed that chromosome changes have occurred during polyploidization process. CONCLUSIONS: The comparative cytogenetic results provide reliable evidence that diploid subspecies caerulea is the direct progenitor of tetraploid subspecies sativa. And autotetraploid ssp. sativa has been suggested to undergo a partial diploidization by the progressive accumulation of chromosome structural rearrangements during evolution. However, the tetraploid subspecies falcata is far from a simple autopolyploid from diploid subspecies falcata although no obvious morphological change was observed between these two subspecies.