Nano-sized microplastics exposure induces skin cell senescence via triggering the mitochondrial localization of GSDMD.

Nano-sized microplastic pollution is distributed worldwide. Nano-sized microplastics can enter the blood through the digestive tract, and then transported to various tissues and organs of the body, resulting in a series of toxicological effects. In addition, nano-sized microplastics can penetrate the skin barrier. However, the toxicological effects of nano-sized microplastics on the skin are still not completely understood. Two skin cell lines were used as in vitro models to investigate the toxicological effects of nano-sized microplastics on skin cells and their potential molecular mechanisms. First, cellular behavioral research results showed that nano-sized microplastics can be internalized into skin cells in a time- and dose-dependent manner. Further experiments using western blotting, indirect immunofluorescence, and ELISA assays demonstrated that nano-sized microplastics cause an increase in skin cell inflammation levels. Additionally, our research showed that nano-sized microplastics caused skin cell senescence damage by evaluating aging-marker molecules such as p16 and p21. Subsequently, we studied the potential molecular mechanism by which nano-sized microplastics cause pathological skin injury and found that they induce mitochondrial oxidative stress, depolarize the mitochondrial membrane potential, and recruit GSDMD to the mitochondria. Subsequently, mtDNA enters the cytoplasm via GSDMD pores, which then activates the AIM2 Inflammasome. Ultimately, it causes a series of biochemical reactions such as inflammation and aging in cells. In an in vivo model, we tested the effect of nano-sized microplastics on skin regeneration and found that they acted as an inhibitor to skin regeneration and aggravated the inflammatory reaction of the skin. Overall, our results provide new evidence of the skin toxicity of nano-sized microplastics. This study provides a theoretical foundation for further research on the potential toxicological effects of nano-sized microplastics on the skin.

Advancements and current trends in tumor treating fields: a scientometric analysis.

Tumor treating fields (TTFields) therapy is a novel and effective noninvasive cancer therapy, and it has been approved by FDA in the treatment of recurrent and newly diagnosed glioblastoma, and malignant pleural mesothelioma. Moreover, TTFields therapy has been widely studied in both clinical trials and preclinical studies in recent years. Based on its high efficacy, research on TTFields therapy has been a hot topic. Thus, the authors made this scientometric analysis of TTfields to reveal the scientometric distributions such as annual publications and citations, countries and institutions, authors, journals, references, and more importantly, research status and hot topics of the field. In recent years, publication numbers have been stable at high values, and citation numbers have been increasing greatly. The United States and Israel were the top two countries with the highest publication numbers, followed by Germany and Switzerland. Scientometric analyses of keywords indicated that clinical applications and antitumor mechanisms are probably the two main parts of current research on TTfields. Most clinical trials of TTfields focus on the treatment of glioblastoma. And a variety of other cancers such as lung cancer especially nonsmall cell lung cancer, hepatic cancer, other brain tumors, etc. have also been studied in both clinical trials and preclinical studies.

Hepatitis D virus dual-infection among Chinese hepatitis B patient related to hepatitis B surface antigen, hepatitis B virus DNA and age.

BACKGROUND: The screening practices for hepatitis D virus (HDV) are diverse and non-standardized worldwide, and the exact prevalence of HDV is uncertain. AIM: To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D. METHODS: We collected 5594 serum samples from patients with hepatitis B in Jilin Province, China (3293 males and 2301 females, age range of 2 to 89 years). We then conducted tests for hepatitis B surface antigen (HBsAg), hepatitis B Virus (HBV) DNA, anti-hepatitis D antigen (HDAg), and HDV RNA. RESULTS: We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6% (3.2-4.2%) and 1.2% (0.9-1.5%), respectively, 87.69% of hepatitis D patients were 51-70 years old. HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL (2.0%) was higher than those above 2000 IU/mL (0.2%). Among anti-HDAg positive patients, the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level. There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients. CONCLUSION: Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection, comprehensive evaluation of patients' clinical and laboratory parameters is necessary for proper diagnosis and treatment.

Cytotoxicity of alkaline serine protease (ASPNJ) on Jurkat cells and its correlation with changes in the expression of membrane-associated proteins.

We aim to study the inhibitory effect of alkaline serine protease (ASPNJ) on lymphocytic leukemia Jurkat cells and its related mechanism through examining the expression of membrane proteins or membrane-associated proteins. MTT assay and trypan blue staining were used to detect the inhibitory effect of ASPNJ on the proliferation and growth of Jurkat cells. Wright-Giemsa staining was used to observe the effect of ASPNJ on the morphology of Jurkat cells. The effect of ASPNJ on Jurkat cell apoptosis was detected by flow cytometry. Two-dimensional electrophoresis-mass spectrometry (2-DE-MS) was used to detect and identify the differentially expressed proteins of Jurkat cells treated with ASPNJ (4 µg/mL, 3 h), of which three were selected and verified by Western blot. ASPNJ significantly inhibited the proliferation of leukemia cells (Raji, U937, and Jurkat), caused obvious morphological changes, and induced apoptosis of Jurkat cells. ASPNJ also increased the sensitivity of Jurkat cells to vincristine (VCR). Seven differentially expressed proteins were obtained through 2DE-MS, of which Peroxiredoxin-6 (PRDX6), Calcium-binding protein (CHP1), and 40S ribosomal protein SA (RPSA) were validated. ASPNJ can cause significant toxic effects on Jurkat cells and enhance the effects of VCR. The mechanism of action of ASPNJ on Jurkat cells may be related to differentially expressed proteins such as PRDX6. This study provides a new experimental basis and direction for antileukemia research.

A novel detection method for neuronal death indicates abnormalities in intracellular membranous components in neuronal cells that underwent delayed death.

Acute neuronal degeneration is always preceded under the light and electron microscopes by a stage called microvacuolation, which is characterized by a finely vacuolar alteration in the cytoplasm of the neurons destined to death. In this study, we reported a method for detecting neuronal death using two membrane-bound dyes, rhodamine R6 and DiOC6(3), which may be associated with the so-called microvacuolation. This new method produced a spatiotemporally similar staining pattern to Fluoro-Jade B in kainic acid-damaged brains in mice. Further experiments showed that increased staining of rhodamine R6 and DiOC6(3) was observed only in degenerated neurons, but not in glia, erythrocytes, or meninges. Different from Fluoro-Jade-related dyes, rhodamine R6 and DiOC6(3) staining is highly sensitive to solvent extraction and detergent exposure. Staining with Nile red for phospholipids and filipin III for non-esterified cholesterol supports that the increased staining of rhodamine R6 and DiOC6(3) might be associated with increased levels of phospholipids and free cholesterol in the perinuclear cytoplasm of damaged neurons. In addition to kainic acid-injected neuronal death, rhodamine R6 and DiOC6(3) were similarly useful for detecting neuronal death in ischemic models either in vivo or in vitro. As far as we know, the staining with rhodamine R6 or DiOC6(3) is one of a few histochemical methods for detecting neuronal death whose target molecules have been well defined and therefore may be useful for explaining experimental results as well as exploring the mechanisms of neuronal death.

Immunotherapy in cervical cancer: From the view of scientometric analysis and clinical trials.

Background: Cervical cancer is the fourth most cancer and the fourth leading cause of cancer-related deaths in women worldwide. Current treatment for patients with advanced cervical cancer is limited. And in the urgent demand for novel effective therapies both as the first and the second line treatment for these patients, immunotherapy is developing fast and has made some achievements. Methods: This study incorporated 1,255 topic-related articles and reviews from 1999 to 2022 in the Web of Science Core Collection (WoSCC). The WoS platform, Citespace, and VOS viewer provided the annual distribution of publications and citations, the analysis of researching countries and institutions, references, keywords (co-occurrence analysis, burst analysis, and timeline view analysis), and researching authors, respectively. For clinical trials, 720 trials and 114 trials from ClinicalTrials.gov and ICTRP were retrieved, respectively. And 296 trials were finally incorporated into the analysis. Results: The scientometric analysis showed that the study of immunotherapies in cervical cancer developed fast in recent years. Most publications were from the United States, followed by China. Seven of the top 10 co-cited references belong to clinical trials, and five of them were published in recent five years. There are lots of clinical trials us specific treatment patterns, some of which have represented excellent effects. Conclusions: Both the scientometric analysis of the 1,255 publications and the analysis of clinical trials showed that the field of immunotherapies in cervical cancer developed so fast in recent years. It was found that a lot of clinical trials using various immunotherapies (mainly vaccine therapy, adoptive cell therapy, immune checkpoint blockade, and antibody-drug conjugate) for advanced cervical cancer are currently ongoing or have represented considerable effect. Centered in immunotherapies, immune checkpoint blockades have represented great efficacy and huge potential, especially combined with other therapies such as chemotherapy, targeted therapy, and other immunotherapies.

Emerging trends and research foci of epithelial-mesenchymal transition in gliomas: A scientometric analysis and review.

Background: Epithelial-mesenchymal transition (EMT) is a key factor in the invasion and migration of glioma cells, and the study of EMT in gliomas has become a hot topic over the past decade. Scientometric analysis is gaining more attention since it can obtain hot topics and emerging trends in a research field. This article analyzed the research related to EMT in gliomas for the first time, including descriptions of research situations, evaluations of research foci, and predictions of emerging trends. Methods: We searched the topic-related original articles from January 2012 to December 2021 in the Web of Science Core Collection (WoSCC) by using a specific strategy, and a total of 1,217 publications were obtained. The WoS platform, VOS viewer, and CiteSpace were used to analyze the annual distribution of publications and citations, authors and density of keywords, and other analyses including countries, institutions, references, clustering, burst analysis, and the timeline view of keywords. Results: Scientometric analysis identified that the study of EMT in gliomas has developed fast and received continuous attention in the last decade. Based on the results of data analysis, most publications on the topic came from China, and the United States had the highest betweenness centrality. The top 10 co-cited references revealed the landmark documents that had greatly promoted the development of this field. The major focus is on the cellular and molecular mechanisms of EMT in gliomas, and the therapy related to EMT target and non-coding RNAs has been developing fast in recent years. Conclusions: This study revealed the intimate connections between EMT and gliomas, and the complex mechanisms regulating EMT in gliomas had been studied widely in the last decade. Exploring the deep mechanisms of EMT in gliomas is the foundation of the targeted inhibitions, which can promote the development of therapies for gliomas.

Early Summer Temperature Variation Recorded by Earlywood Width in the Northern Boundary of Pinus taiwanensis Hayata in Central China and Its Linkages to the Indian and Pacific Oceans.

The Tongbai Mountains are an ecologically sensitive region to climate change, where there lies a climatic transitional zone from a subtropical to a warm−temperate monsoon climate. The northern boundary of Pinus taiwanensis Hayata is here; thus, climate information is well recorded in its tree rings. Based on developed earlywood width (EWW), latewood width (LWW) and total ring width (RW) chronologies (time period: 1887−2014 year) of Pinus taiwanensis Hayata in the Tongbai Mountains in central China, this paper analyzed characteristics of these chronologies and correlations between these chronologies and climate factors. The correlation results showed that earlywood width chronology contains more climate information than latewood width chronology and total ring width chronology, and mean temperature and mean maximum temperature in May−June were the main limiting factors for radial growth of Pinus taiwanensis Hayata. The highest significant value in all correlation analyses is −0.669 (p < 0.05) between earlywood width chronology and May−June mean temperature (TMJ) in the pre-mutation period (1958−2005) based on mutating in 2006. Thus, this paper reconstructed May−June mean temperature using earlywood width chronology from 1901 to 2005 (reliable period of earlywood width chronology is 1901−2014). The reconstructed May−June mean temperature experienced eight warmer periods and eight colder periods and also showed 2−3a cycle change over the past 105 years. The spatial correlation showed that the reconstructed series was representative of the May−June mean temperature variation in central and eastern China and significant positive/negative correlation with the sea surface temperature (SST) of the subtropical Pacific Ocean and the tropical Western Pacific Ocean and Indian Ocean from the previous October to the current June. This also indicated that May−June mean temperature periodic fluctuations might be related to the quasi-biennial oscillation (QBO) in the tropical Western Pacific Ocean and Indian Ocean. The results of this study have extended and supplemented the meteorological records of the Tongbai Mountains and have a guiding significance for forest tending and management in this area.

Climate-Growth Relationships of Chinese Pine (Pinus tabulaeformis Carr.) at Mt. Shiren in Climatic Transition Zone, Central China.

Tree ring data from the southern boundary of Chinese Pine (Pinus tabulaeformis Carr.) distribution where is the southern warm temperate margin, the paper analyzes the response of climate factors along north-south direction to tree growth. The results show that temperature and precipitation in May-June and relative moisture from March to June are main limiting factors on trees growth; however, the temperature in the south of the mountains and the moisture in the north of the mountains have relatively greater influence on trees' growth. Additionally, we also found that the regional scPDSIMJ (that is scPDSI in May-June) was the most significant and stable factor limiting tree growth to be used for reconstruction. The reconstructed scPDSIMJ revealed that there were 29 extremely dry years and 30 extremely wet years during 1801-2016, and it could represent the drought variation in central and eastern monsoon region. The variation exists in good agreement with the reconstructed PDSI for Mt. Shennong and the drought/wetness series in Zhengzhou. Further research found that the droughts of May-June in central China were mainly impacted by local temperature and moisture (including precipitation, soil moisture, potential evaporation and water pressure), and then by the northern Pacific Ocean and the northern Atlantic Ocean. These results may provide better understanding of May-June drought variation and service for agricultural production in central China.

[Responses of tree-ring width of Pinus tabuliformis plantation to climatic factors in Songshan Mountains, central China]. / åµ©å±±åœ°åŒºæ²¹æ¾äººå·¥æž—æ ‘è½®å®½åº¦å¯¹æ°”å€™å› å­çš„å“åº”.

Taking Pinus tabuliformis plantations at different slopes in Songshan Mountains, Henan Province, China as subjects, we established different residual chronologies of P. tabuliformis in Paomaling (PML) and Junjifeng (JJF) and whole region (RC). The results showed that the chro-nological quality of PML was higher than that of JJF. Chronologies of PML and JJF had more climate information, which had significant positive relationship with mean temperature in current February, mean temperature and mean maximum temperature at the end of growing season (September-October), and significant negative relationship with mean maximum temperature in current May. The response of radial growth of P. tabuliformis to climate differed in PML and JJF. Radial growth of P. tabuliformis in PML was positively correlated with mean minimum temperature in March and precipitation in September, while that in JJF was positively correlated with precipitation in May and mean minimum temperature in September. Residual chronologies of P. tabuliformis in whole region contained more climate information. The multiple regression analysis method was used to simulate that the main limiting factors of tree-ring width growth of P. tabuliformis, which was a range of temperature indicators, especially current mean temperature in September. The result was consistent with that of correlation analysis. This study could provide basic services for forest protection and ecological construction in Songshan Mountains region.

[Responses of radial growth of two coniferous species to climate factors in western Sichuan Plateau, China]. / å·è¥¿é«˜åŽŸä¸¤ç§é’ˆå¶æ ‘å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å› å­çš„å“åº”.

Based on the method of tree-ring chronology, we established ring-width standard chrono-logies of Abies faxoniana and Sabina saltuaria in Liangtaigou, Lixian County, western Sichuan Province, and their regional composite chronology (RC) to study the responses of radial growth of those two coniferous species to climate change, which provided a basis for the protection and mana-gement of forest ecosystems in this region under the background of global warming. The results showed that the RC contained the common climatic information of two individual chronologies, which had higher signal-to-noise ratio and expressed population signal. The correlation analysis showed that three chronologies had a good consistency in the response to climate factors. All chronologies were significantly correlated with temperature, with S. saltuaria being more sensitive to temperature changes. Relative humidity had stronger limiting effect on both species than precipitation in May and October. After the abrupt warming in 1994, the correlation between ring-width chrono-logy of A. faxoniana and monthly mean temperature shifted obviously from negative to positive in some months, which indicated the radial growth of A. faxoniana showed unstable in response to temperature. However, the radial growth of both species showed different broadening trend and the sensitivity to temperature response was weakened.

ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.

Bloodstream infection (BSI) is usually accompanied with the changes of varieties of inflammation proteins. In our previous study, we identified that inter-α-trypsin inhibitor heavy chain H4 (ITIH4) was highly expressed in the infection arms than the normal control arm. However, the correlated verification and mechanism remain obscure. Escherichia coli infected mice model and clinical serum samples were used to validate the concentration of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), as well as ITIH4, in ELISA method. Cytokines (IL-6, TNF-α, IL-10 and lipopolysaccharide (LPS)) were used to stimulate the HepG2 cell model to explore which cytokines influence the expression of ITIH4. JAK/STAT inhibitor was treated before IL-6 and LPS stimulation. Westernblot, as well as real-time PCR were performed to detect the expression of ITIH4 in liver tissue from protein and transcription levels. Immunohistochemistry analysis was used to observe the expression of ITIH4 in mice liver tissue. In mice model, IL-6, TNF-α, as well as IL-10 increased in the infection arms than the normal control arm. ITIH4 in serum and liver tissue of mice model increased from 1 h to 128 h, which were remarkably different from that of the normal control arm. Besides, ITIH4 increased in the bacterial infection arm greatly than the fungemia arm, mycoplasma pneumoniae (MP) arm and febrile arm in clinical serum samples. Furthermore, using the HepG2 cell line, we demonstrated that ITIH4 was up-regulated at both protein and mRNA levels upon dose- and time- response treatments with IL-6, as well as LPS. Moreover, IL-6 or LPS mediated induction of ITIH4 expression could be significantly decreased by treatment with an JAK/STAT inhibitor in protein or mRNA level. No changes were observed after TNF-α or IL-10 stimulation. ITIH4 might be a critical inflammatory biomarker which correlated with the development of BSI, especially with bacterial bloodstream infection. It is expected that this study would provide some insights into potential functional mechanisms underlying BSI.

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.

Induction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondria to nuclei in glioma cells in vitro and in vivo, which is accompanied with autophagy activation. In vitro studies reveal that blocking autophagy with 3MA, bafilomycin A1 or by knocking down ATG5 with SiRNA inhibits silibinin-induced mitochondrial accumulation of superoxide, AIF translocation from mitochondria to nuclei and glioma cell death. Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis. Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT. The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria. Knockdown of BNIP3 with SiRNA inhibits silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide, and AIF translocation from mitochondria to nuclei, as well as prevents glioma cell death. Furthermore, we find that the improved H2O2 reinforces silibinin-induced glycolysis dysfunction. Collectively, autophagy contributes to silibinin-induced glioma cell death via promotion of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.

Diagnostic efficacy of serum cytokines and chemokines in patients with candidemia and bacteremia.

BACKGROUND: The role of serum cytokines/chemokines in differential diagnosis between fungal infections and bacterial infections have not been fully understood. This study aims to measure the serum levels of cytokines/chemokines in cases of candidemia and to compare them with those observed in cases of bacteremia. MATERIAL AND METHODS: Patients with febrile episodes and were identified as bloodstream infections through blood culture were enrolled, while healthy people were included as control group. Fourteen serum cytokine and chemokine levels were detected with multiplex platform. ROC analysis was performed and an area under the curve (AUC), sensitivity and specificity values were calculated to determine the efficacy of various cytokines and chemokines for candidemia and bacteremia. Binary logistic regression was performed to further explore the combination mode of cytokines and chemokines, which could increase the diagnostic efficiency. RESULTS: We included 40 patients with an episode of microbiologically proven fungal infection, 175 patients with bacteremia (85 with Gram-positive bacteremia and 90 with Gram-negative bacteremia) and another 30 healthy controls. Routine laboratory parameters including CRP and PCT were not statistically significant between candidemia group and bacteremia group (both gram-positive and gram-negative). There were significantly higher levels of IFN-γ, TNF-α, IL-10 and lower levels of IL-3, IL-4 in candidemia group, compared with gram-positive and gram-negative bacteremia groups. G-CSF was significantly lower and MIP-1ß was higher in candidemia group, when compared with gram-negative bacteremia group. While IL-6, IL-8 and IL-17 were all significantly higher in candidemia group, when compared with gram-positive bacteremia group. Combination of IFN-γ and IL-17 could improve the diagnostic efficiency between candidemia and gram-positive bacteremia, with the AUROC of 0.873 (95% CI: 0.767-0.929). While combination of G-CSF and MIP-1ß improved the diagnostic efficiency between candidemia and gram-negative bacteremia, with the AUROC of 0.896 (95% CI: 0.792-0.939). CONCLUSION: Our study demonstrates that serum cytokines and chemokines including IFN-γ, MIP-1ß, IL-17 and G-CSF could be considered as diagnostic markers to distinguish between candidemia and bacteremia. Combination of these biomarkers might improve the diagnostic efficiency of candidemia when compared with bacteremia.

Different cellular properties and loss of nuclear signalling of porcine epidermal growth factor receptor with aging.

Epidermal growth factor (EGF) has important physiological functions that are mediated by the epidermal growth factor receptor (EGFR); however, to date, the changes in cellular behaviours and signalling properties of EGF/EGFR with aging remain unclear in the pig tissue models. Hence, the present study used porcine hepatocytes as a model to explore this issue. The study revealed the following results: 1) EGF could activate the intra-cellular signalling pathways in a time- and dose-dependent manner both in the young- and aged-pig hepatocytes, EGF induced tyrosine phosphorylation of EGFR, signal transducers and activators of transcription 3 (STAT3), protein kinase B (AKT) and extra-cellular signal-regulated kinase 1/2 (ERK1/2). Nevertheless, the EGF's signalling ability in the aged-pig hepatocytes was significantly reduced compared with that of the young-pig hepatocytes; 2) although EGF/EGFR can still be internalised into cells in a time-dependent manner with aging, the endocytic pathway differs between the young- and aged-pig hepatocytes. Furthermore, the results of the present study indicated that caveolin may play a pivotal role in the endocytosis of EGF/EGFR in the aged-pig hepatocytes, which is different from that of EGF/EGFR's endocytosis in young-pig hepatocytes; 3) It is well-known that EGFR carried out its biological effects via two signalling pathways, cytoplasmic pathway (traditional) and nuclear pathway; however, we found that the nuclear localisation of EGFR was significantly reduced in the aged-pig hepatocytes, which indicated that EGFR may lose its nuclear pathway with aging. Collectively, the present study lays the foundation for further study regarding the biological functional changes occurring in EGF/EGFR with aging.

Diagnostic efficacy of serum cytokines and chemokines in fungal bloodstream infection in febrile patients.

BACKGROUND: The role of serum cytokines/chemokines in early diagnosis of fungal infections has not been clearly clarified yet. This study aims to measure the serum levels of cytokines/chemokines in cases of fungemia and to compare them with culture-negative controls. METHODS: In total, fourteen types of serum cytokines and chemokines from 41 patients with fungemia were compared with 57 patients with negative blood culture results. The cytokine and chemokine levels were detected with multiplex platform. We then performed statistical analysis as a two-tailed P < .05. ROC analysis was performed, and an area under the curve (AUC), and sensitivity and specificity values were calculated to determine the efficacy of various cytokines and chemokines for fungemia. Binary logistic regression was performed to further explore the combination mode of cytokines and chemokines, which could increase the diagnostic efficiency. RESULTS: C-reactive protein and procalcitonin were significantly higher compared with those in negative control group, while white blood cell, percentage of neutrophil, percentage of lymphocyte, and ratio of neutrophil and lymphocyte did not differentiate between two groups. Serum levels of IFN-γ, TNF-α, MIP-1ß, IL-6, IL-8, IL-10, IL-12p70, and IL-17 were significantly higher in patients with fungemia compared with the control group. Combination of MIP-1ß and IL-17 could improve the AUC, sensitivity, and specificity for the diagnosis of fungemia. CONCLUSION: Our study demonstrates that serum cytokines and chemokines including IFN-γ, TNF-α, MIP-1ß, IL-6, IL-8, IL-10, IL-12p70, and IL-17 could be considered as diagnostic markers for fungemia. Combination of these biomarkers might improve the diagnostic efficiency of fungemia.

Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling.

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-ß1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signaling in vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experiments in vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.

Familial intracranial arachnoid cysts with a missense mutation (c.2576C > T) in RERE: A case report.

RATIONALE: Arachnoid cysts are relatively common intracranial space-occupying lesions; nevertheless, familial intracranial arachnoid cysts are extremely rare, with only a few cases having been reported. PATIENT CONCERNS: The proband was a 7-year-old girl who had experienced generalized tonic-clonic seizures 5 times in the 8 days prior to admission. Nine months later, her 6-year-old younger female cousin presented to us with a 3-day history of headache. DIAGNOSES: Brain magnetic resonance imaging (MRI) confirmed the diagnosis of arachnoid cyst for both of the girls. INTERVENTIONS: A cyst-peritoneal shunting and cyst fenestration were performed for the 7-year-old girl and her cousin separately. Sanger sequencing revealed a heterozygous missense mutation (c.2576C > T) in the Arginine-Glutamic Acid Dipeptide Repeats gene (RERE). OUTCOMES: The outcome was favorable and the follow-up was uneventful. LESSONS: We hypothesize that the mutation in RERE may be associated with the pathogenesis of familial intracranial arachnoid cysts.

Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the common primary brain tumor classified the most malignant glioma. Long non-coding RNAs (LncRNAs) are important epigenetic regulators with critical roles in cancer initiation and progression. LncRNA HOTAIRM1 transcribes from the antisense strand of HOXA gene cluster which locus in chromosome 7p15.2. Recent studies have shown that HOTAIRM1 is involved in acute myeloid leukemia and colorectal cancer. Here we sought to investigate the role of HOTAIRM1 in GBM and explore its mechanisms of action. METHODS: The expressions of HOTAIRM1 and HOXA1 in GBM tissues and cells were determined by qRT-PCR, and the association between HOTAIRM1, HOXA1 transcription and tumor grade were analyzed. The biological function of HOTAIRM1 in GBM was evaluated both in vitro and in vivo. Chromatin immunoprecipitation (ChIP) assay and quantitative Sequenom MassARRAY methylation analysis were performed to explore whether HOTAIRM1 could regulate histone and DNA modification status of the HOXA1 gene transcription start sites (TSS) and activate its transcription. ChIP and RNA-ChIP were further performed to determine the molecular mechanism of HOTAIRM1 in epigenetic regulation of the HOXA1 gene. RESULTS: HOTAIRM1 was abnormally up-regulated in GBM tissues and cells, and this up-regulation was correlated with grade malignancy in glioma patients. HOTAIRM1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. In vivo experiments showed knockdown of HOTAIRM1 lessened the tumor growth. Additionally, HOTAIRM1 action as regulating the expression of the HOXA1 gene. HOXA1, as an oncogene, it's expression levels were markedly elevated in GBM tissues and cell lines. Mechanistically, HOTAIRM1 mediated demethylation of histone H3K9 and H3K27 and reduced DNA methylation levels by sequester epigenetic modifiers G9a and EZH2, which are H3K9me2 and H3K27me3 specific histone methyltransferases, and DNA methyltransferases (DnmTs) away from the TSS of HOXA1 gene. CONCLUSIONS: We investigated the potential role of HOTAIRM1 to promote GBM cell proliferation, migration, invasion and inhibit cell apoptosis by epigenetic regulation of HOXA1 gene that can be targeted simultaneously to effectively treat GBM, thus putting forward a promising strategy for GBM treatment. Meanwhile, this finding provides an example of transcriptional control over the chromatin state of gene and may help explain the role of lncRNAs within the HOXA gene cluster.