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1.
Biomed Pharmacother ; 125: 109924, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018221

RESUMO

High-glucose induced retinal pigment epithelium (RPE) death by triggering oxidative stress, however, the underlying mechanisms are still not fully delineated. In this study, the RPE cell line ARPE-19 were treated with different concentrations of glucose, the results showed that high-glucose (50 mM) inhibited cell proliferation, promoted cell apoptosis and reactive oxygen species (ROS) production in a time-dependent manner. Notably, we found that high-glucose (50 mM) increased the expression levels of Caspase-1, Gasdermin D, NLRP3, IL-1ß and IL-18 in ARPE-19 cells, which indicated that high-glucose triggered pyroptotic cell death. Further results validated that both ROS scavenger N-acetyl cysteine (NAC) and pyroptosis inhibitor necrosulfonamide (NSA) reversed the effects of high-glucose (50 mM) on ARPE-19 cell proliferation, apoptosis and pyroptosis. In addition, high-glucose (50 mM) significantly decreased the levels of miR-130a and superoxide dismutase (SOD) 1, and promoted tumor necrosis factor (TNF)-α expressions in ARPE-19 cells. Interestingly, upregulation of miR-130a increased SOD1 levels in a TNF-α dependent manner. Furthermore, overexpression of miR-130a abrogated the effects of high-glucose (50 mM) on the above cell functions, which were all reversed by either upregulating TNF-α or knocking down SOD1 in ARPE-19 cells. Taken together, upregulation of miR-130a alleviated the cytotoxic effects of high-glucose (50 mM) on ARPE-19 cells by regulating TNF-α/SOD1/ROS axis mediated pyroptotic cell death.

2.
Am J Pathol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035060

RESUMO

Liver regeneration is a fundamental biological process required for sustaining body homeostasis and restoring liver function after injury. Emerging evidence demonstrates that cytokines, growth factors and multiple signaling pathways contribute to liver regeneration. Mammalian target of rapamycin complex 2 (mTORC2) was identified to regulate cell metabolism, proliferation and survival. The major substrates for mTORC2 are the AGC-family members of kinases, including AKT, SGK and PKC-α. Here, we investigated the functional roles of mTORC2 during liver regeneration. For this purpose, we performed partial hepatectomy (PHx) in liver specific Rictor (the pivotal unit of mTORC2 complex) knockout (RictorLKO) and wild-type (Rictorfl/fl) mice. We discovered that Rictor deficient mice are more intolerant to PHx and display higher mortality after PHx. Mechanistically, loss of Rictor resulted in decreased Akt phosphorylation, leading to a delay in hepatocyte proliferation and lipid droplets formation along liver regeneration. Overall, these results indicate an essential role of the mTORC2 signaling pathway during liver regeneration.

3.
Med Sci Monit ; 26: e922426, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32038049

RESUMO

BACKGROUND Schizophrenia is a multigene disease with a complex etiology and different clinical manifestations. It is of great significance to understand the etiology and pathogenesis of schizophrenia patients from different clinical dimensions and to interpret the potential molecular changes of schizophrenia patients from different clinical dimensions. MATERIAL AND METHODS RNA-Seq was performed on peripheral blood leukocytes of 50 patients with schizophrenia and 50 healthy controls. Phenotypic information of patients with schizophrenia was collected during blood sampling. Differentially expressed genes (DEGs) were screened by the edgeR package of R software. To better analyze the correlation between DEG expression values, explore the potential association between differential genes and clinical dimensions of schizophrenia, and identify hub genes, we constructed a DEG co-expression network using weighted gene co-expression network analysis (WGCNA). RESULTS We provide the transcription profiles of peripheral blood leukocytes in patients with schizophrenia and found a gene module (including 89 genes) closely related to the clinical dimension of abnormal psychomotor behavior in schizophrenia. CONCLUSIONS The findings enhance our understanding of the biological processes of schizophrenia, enabling us to identify specific clinical dimensions of genes for diagnosis and prognostic markers and possibly for targeted therapy.

4.
Ann Surg Oncol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016632

RESUMO

BACKGROUND: Whether hepatic resection (HR) combined with radiofrequency ablation (RFA) or HR alone is the treatment of choice for early or moderately advanced multifocal hepatocellular carcinomas (HCCs) is a matter of debate. This study compared the short- and long-term outcomes of patients with multifocal tumors meeting the University of California San Francisco (UCSF) criteria after HR plus intraoperative RFA or HR alone. METHODS: A total of 261 consecutive patients with multifocal HCCs meeting the UCSF criteria from January 2010 to January 2018, who underwent combined treatment (n = 51) or HR (n = 210), were included. Propensity score matching was performed to adjust for baseline differences. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and subgroup analysis, along with univariate and multivariate analyses, were performed. RESULTS: The 1-, 3-, and 5-year OS rates after combined treatment or HR alone were 86.3%, 66.6%, and 34.2%, and 92.8%, 67.1%, and 37%, respectively (p = 0.423); combined treatment provided similar RFS rates as HR at 1, 3, and 5 years (78.4%, 35.8% and 20.9% vs. 82.6%, 50.4% and 24.5%, respectively; p = 0.076). The propensity matching model showed similar results. Subgroup analysis showed that HR was associated with better RFS than HR plus RFA for patients with two tumors or major tumors ≤ 3 cm. Multivariate analysis revealed that portal hypertension and three tumors are independent risk factors. CONCLUSIONS: For multifocal HCC patients meeting the UCSF criteria, combined treatment may offer similar OS and RFS as HR; however, HR may be more suitable than combined treatment for patients with two tumors or major tumors ≤ 3 cm.

5.
Ann Surg Oncol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916093

RESUMO

OBJECTIVE: The aim of this study was to develop quantitative feature-based models from histopathological images to distinguish hepatocellular carcinoma (HCC) from adjacent normal tissue and predict the prognosis of HCC patients after surgical resection. METHODS: A fully automated pipeline was constructed using computational approaches to analyze the quantitative features of histopathological slides of HCC patients, in which the features were extracted from the hematoxylin and eosin (H&E)-stained whole-slide images of HCC patients from The Cancer Genome Atlas and tissue microarray images from West China Hospital. The extracted features were used to train the statistical models that classify tissue slides and predict patients' survival outcomes by machine-learning methods. RESULTS: A total of 1733 quantitative image features were extracted from each histopathological slide. The diagnostic classifier based on 31 features was able to successfully distinguish HCC from adjacent normal tissues in both the test [area under the receiver operating characteristic curve (AUC) 0.988] and external validation sets (AUC 0.886). The random-forest prognostic model using 46 features was able to significantly stratify patients in each set into longer- or shorter-term survival groups according to their assigned risk scores. Moreover, the prognostic model we constructed showed comparable predicting accuracy as TNM staging systems in predicting patients' survival at different time points after surgery. CONCLUSIONS: Our findings suggest that machine-learning models derived from image features can assist clinicians in HCC diagnosis and its prognosis prediction after hepatectomy.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 42-46, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948523

RESUMO

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.


Assuntos
Hipersensibilidade a Leite , Animais , Bovinos , China , Feminino , Humanos , Lactente , Proteínas do Leite , Gravidez , Fatores de Risco , Inquéritos e Questionários
9.
HPB (Oxford) ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31980306

RESUMO

BACKGROUND: Aging of the population and prolonged life expectancy have significantly increased the number of elderly patients undergoing hepatectomy for hepatocellular carcinoma (HCC). However, potential benefits, especially long-term oncologic outcomes of hepatectomy for elderly patients with HCC remain unclear. METHOD: Patients treated with curative-intent hepatectomy for HCC in 8 Chinese hospitals were enrolled. Patients were divided into the elderly (≥70 years old) and younger (<70 years old) groups. Overall survival (OS), cancer-specific survival (CSS), and time-to-recurrence (TTR) were compared. Risk factors of CSS and TTR were evaluated by univariable and multivariable competing-risk regression analyses. RESULTS: Of 2134 patients, 259 (12.1%) and 1875 (87.9%) were elderly and younger aged, respectively. Postoperative 30-day and 90-day mortality was comparable among elderly and younger patients. Compared with younger patients, the elderly had a worse 5-year OS (49.4% vs. 55.3%, P = 0.032), yet a better 5-year CCS (74.5% vs. 61.0%, P = 0.005) and a lower 5-year TTR (33.7% vs. 44.9%, P < 0.001), respectively. Multivariable analyses identified that elder age was independently associated with more favorable CSS (HR 0.74, 95%CI 0.58-0.90, P = 0.011) and TTR (0.69, 0.53-0.88, P < 0.001) but was not associated with OS (P = 0.136). CONCLUSIONS: Age by itself is not a contraindication to surgery, and selected elderly patients with HCC can benefit from hepatectomy. Compared with younger patients, elderly patients have noninferior oncologic outcomes following hepatectomy for HCC.

10.
J Ethnopharmacol ; 250: 112478, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31843572

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-tai-wan is a well-known traditional Chinese herbal medicine formula that is used to treat insomnia and systemic inflammation. Studies indicate chronic insomnia might contribute to the prevalence of cognitive impairment. The role of systemic inflammation and intestinal permeability in the progression of neurodegenerative diseases attracts much attention. AIM OF THE STUDY: This study aimed to investigate if Jiao-tai-wan plays a role in promoting the repair of the intestinal epithelial barrier to suppress systemic inflammation and cognitive impairment in sleep-deprived (SD) rats. MATERIALS AND METHODS: Male obesity-resistant SD rats were partially sleep-deprived for 16 weeks. During the last 8 weeks, they were treated with Jiao-tai-wan. A Morris water maze was used to analyze their cognitive ability. Aß42 and proinflammation cytokines in the cerebrospinal fluid, tissue, or serum were determined using enzyme-linked immunosorbent assay or polymerase chain reaction. Intestinal permeability was detected using the fluorescein isothiocyanate-dextran perfusion assay method. Plasma lipopolysaccharide (LPS) levels were detected with Tachypleus Amebocyte Lysate. Western bolt was used in the signaling pathway analysis. RESULTS: Sleep deprivation deteriorated the performance of rats in the Morris water maze and increased the Aß42, caspase3, IL-6, and TNF-α levels in their brains. The intestinal TLR4/NF-κB pathway was activated with an increase in the expression of IL-6 and TNF-α. The expression of tight junction proteins was also decreased in the intestinal tissue. This increased the intestinal permeability and circulation of LPS, LPS binding protein, IL-6, and TNF-α. Treatment with Jiao-tai-wan could partly reverse these changes. CONCLUSION: Jiao-tai-wan has the potential to attenuate systemic inflammation and cognitive impairment in partially sleep-deprived rats. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.

11.
Polymers (Basel) ; 11(12)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795517

RESUMO

Recently, the nanofiber materials derived from natural polymers instead of petroleum-based polymers by electrospinning have aroused a great deal of interests. The lignocellulosic biomass could not be electrospun into nanofiber directly due to its poor solubility. Here, sugarcane bagasse (SCB) was subjected to the homogeneous esterification with different anhydrides, and the corresponding esterified products (SCB-A) were obtained. It was found that the bead-free and uniform nanofibers were obtained via electrospinning even when the mass fraction of acetylated SCB was 70%. According to the thermogravimetric analyses, the addition of SCB-A could improve the thermal stability of the electrospun composite nanofibers. More importantly, in contrast to the pure polyacrylonitrile (PAN) based carbon nanofiber, the SCB-A based carbon nanofibers had higher electrical conductivity and the surface N element content. In addition, the superfine carbon nanofiber mats with minimum average diameter of 117.0 ± 13.7 nm derived from SCB-A were obtained, which results in a larger Brunauer-Emmett-Teller (BET) surface area than pure PAN based carbon nanofiber. These results demonstrated that the combination of the homogeneous esterification and electrospinning could be a feasible and potential way to produce the bio-based carbon nanofibers directly from lignocellulosic without component separation.

12.
Lung Cancer ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31839416

RESUMO

OBJECTIVES: The 3rd generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR TKI) osimertinib has shown promising efficacy both in EGFR-mutant, T790M positive non-small cell lung cancer (NSCLC) patients who have become resistant to 1st or 2nd generation EGFR TKIs and patients with sensitizing EGFR mutations as the first line therapy. However, the degree and duration of response to osimertinib are heterogeneous. We hypothesized that the concurrent genomic landscape of these tumors could play a role in clinical outcomes and/or mechanisms of resistance. MATERIALS AND METHODS: We conducted a retrospective multicenter study of lung cancer patients who had developed resistance to osimertinib. Genomic profiling was done for all the patients by using targeted next-generation sequencing encompassing 59-1021 cancer-related genes. RESULTS AND CONCLUSION: Known EGFR-dependent resistant mutations and activation of alternative pathways were identified in 44 % of all the patients with great heterogeneity. Gain-of-function mutations of CTNNB1 were highly enriched in our cohort. Some other putative resistance mechanisms to osimertinib, such as the recurrent EGFR V834 L mutation, were also identified. Moreover, pathogenic mutations of TP53 were negatively related to the efficacy of osimertinib. To sum up, heterogeneity of resistance to osimertinib was not only manifested by inter-individual differences, but also embodied in its intra-individual diversity.

13.
Mol Cancer ; 18(1): 186, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856849

RESUMO

BACKGROUND: N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. METHODS: Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. RESULTS: KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3' UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. CONCLUSION: Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.

14.
Electrophoresis ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31845367

RESUMO

Exosome quantification is important for estimation of informative messengers (e.g., proteins, lipids, RNA, etc.) involving physiological and pathological effects. This work aimed to develop a simple and rapid distance-based paper portable device using exosome-capture vesicles (polydiacetylene conjugated with antiCD81) for exosome quantification in cell cultures. This novel concept relied on distinct aggregation of exosomes and exosome-capture vesicles leading to different solvent migration. Distances of the migration were used as signal readouts, which could be detected by naked eye. PDA-antiCD81 as exosome-capture vesicles were optimized (e.g., size, reaction ratio, and concentration) and the paper designs were investigated (e.g., diameter of sample reservoir and lamination layer) to enhance the solvent stop-flow effects. Finally, exosome screening on three cell culture samples (COLO1, MDA-MB-231, and HuR-KO1 subclone) was demonstrated. The method could linearly measure exosome concentrations in correlation with solvent migration distances in the range of 106 -1010 particles/mL (R2  > 0.98) from the cell culture samples. The exosome concentration measurements by the developed device were independently assessed by nanoparticle tracking analysis. Results demonstrated no statistically significant difference (p > 0.05) by t-test. This low-cost and rapid device allows a portable platform for exosome quantification without the requirement of expensive equipment and expertise of operation. The developed device could potentially be useful for quantification of other biomarker-related extracellular vesicles.

15.
Taiwan J Obstet Gynecol ; 58(6): 833-839, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759537

RESUMO

OBJECTIVE: Substantial previous studies have almost reached an agreement on the gender effect on maternal serum human chorionic gonadotropin (MsHCG) in and after the late first trimester of pregnancy. However, there is little knowledge of the sex-related difference in MsHCG level at the preliminary stage of pregnancy. The purpose of this study is to reveal this difference in women after fresh or frozen single blastocyst transfer (SBT). MATERIALS AND METHODS: A total of 252 fresh SBT cycles and 1486 frozen-thawed SBT cycles collected between June 1, 2014 and May 30, 2017 were retrospectively analyzed in our center. Patients with MsHCG level ≥5 IU/L on day 11 after transfer, achieving a singleton intrauterine pregnancy and subsequent live birth were included. We compared MsHCG levels between women gave birth to a male neonate and those gave birth to a female one in fresh or frozen SBT cycles, respectively. RESULTS: A total of 136 neonates including 57 females and 79 males were born following fresh SBT. The male-female ratio was 1.39:1. The average MsHCG level of male fetuses was higher than that of female fetuses on day 11 after transfer (549.82 ± 253.24 IU/L versus 439.03 ± 198.41 IU/L, P < 0.05). Correspondingly, a total of 431 infants was born after frozen SBT, containing 188 females and 243 males. The male-female ratio was 1.29:1. Initial MsHCG level remained higher in women with a male neonate than the counterparts with a female neonate (894.43 ± 622.17 IU/L versus 758.05 ± 624.33 IU/L, P < 0.05). It was also found the pregnant women following frozen-thawed SBT exhibited higher initial MsHCG level than those following fresh SBT in whether male-bearing or female-bearing gestations. CONCLUSIONS: MsHCG levels are higher in pregnant women with a male fetus than those with a female one on day 11 after fresh or frozen SBT. A sex-specific response to the stress in the process of in vitro embryo culture was suggested.

16.
Front Hum Neurosci ; 13: 376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680921

RESUMO

Mindfulness is described as the non-judgmental awareness of experiences in the present moment. The sustained practice of mindfulness may also have beneficial effects on an individual's well-being. For instance, mindfulness meditation is an effective approach for improving emotion regulation. Specifically, the early stage of mindfulness meditation training enhances emotional monitoring systems related to attention regulation and executive function. Reduced activity in the default mode network (DMN) would probably be observed corresponding to the attenuated mind wandering. In the present study, we hypothesized that alterations in functional activity in the frontal-parietal cortex and DMN may be induced by short-term mindfulness meditation. In this study, before and after 8 weeks of weekly Mindfulness-Based Stress Reduction (MBSR) training, healthy participants were evaluated using a mindfulness questionnaire and an affect schedule, as well as via resting-state functional magnetic resonance imaging. Sixteen right-handed non-meditators were enrolled. Another 16 demographically matched healthy adults without any meditation experience were recruited as controls. Pre- and post-MBSR assessments were compared. Increased regional homogeneity in the right superior parietal lobule and left postcentral gyrus (PoCG), as well as altered functional connectivity in PoCG-related networks, were observed post-MBSR. The mindfulness questionnaire scores also improved and negative affect was significantly decreased after MBSR. Together with reduced involvement of the posterior brain, our results suggest a tendency toward stronger involvement of the parietal cortex in mindfulness beginners. This study provides novel evidence regarding the optimization of emotional processing with short-term mindfulness meditation.

17.
Mol Ther Nucleic Acids ; 18: 518-532, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31671345

RESUMO

Long non-coding RNAs (lncRNAs) have been shown to be crucial regulators in numerous human diseases. However, little is known about their effects on early recurrent miscarriage (RM). Here we aimed to investigate the role of lncRNA EPB41L4A-AS1 on placental trophoblast cell metabolic reprogramming, which might be involved in the pathogenesis of RM. After microarray and GEO database analyses, we found that EPB41L4A-AS1 was significantly increased in early RM placental tissue, and this increase may relate to estradiol-mediated upregulation of PGC-1α. EPB41L4A-AS1 overexpression inhibits glycolysis but increases the dependence on fatty acid oxidation in mitochondrion metabolism and suppresses the Warburg effect, which is necessary for rapid growth of the placental villus, leading to miscarriage. Mechanistic analyses demonstrated that EPB41L4A-AS1 functions as a lncRNA in the regulation of VDAC1 and HIF-1α expression through enhancement of H3K4me3 levels in the promoters of VDAC1 and HIF1A-AS1, a natural antisense transcript (NAT) lncRNA of HIF-1α. Taken together, these findings demonstrate that aberrant expression of EPB41L4A-AS1 is involved in the etiology of early RM, and it may be a candidate diagnostic hallmark and a potential therapeutic target for early RM treatment.

18.
Fertil Steril ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31718829

RESUMO

OBJECTIVE: To investigate whether chronic endometritis (CE) affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure (RRF). DESIGN: Retrospective study. SETTING: Private fertility center. PATIENTS(S): A total of 524 RRF patients, including 324 women with recurrent miscarriage (RM) and 200 women with recurrent implantation failure (RIF). INTERVENTION(S): Peripheral blood and endometrium samples were collected in the midluteal phase before in vitro fertilization treatment or pregnancy. The number of peripheral T, natural killer (NK), and B cells, as well as cytotoxicity of NK cells and expression of TH1 cytokines were analyzed with the use of flow cytometry, and uterine immune cells were subjected to immunohistochemistry. MAIN OUTCOME MEASURE(S): Peripheral immune cells, cytokines, NK cytotoxicity, and endometrial immune cells were compared in RRF patients with versus without CE. RESULT(S): The proportion and function of the analyzed immune cell subsets in peripheral blood as well as the percentages of CD56+ NK cells, CD163+ M2 macrophages, and CD1a+ immature dendritic cells in the endometrium were not significantly altered between non-CE and CE patients, whereas the proportions of uterine CD68+ macrophages, CD83+ mature dendritic cells, CD8+ T cells, and Foxp3+ regulatory T cells were significantly elevated in CE patients. After antibiotic treatment, the percentage of CD68+ macrophages, CD83+ mature dendritic cells, CD8+ T cells, and Foxp3+ regulatory T cells in endometrium were significantly reduced in patients with cured CE. CONCLUSION(S): CE contributes to elevated endometrial infiltration levels of immune cells. The excessive presence of endometrial immune cells in CE patients may be involved in reduced endometrial receptivity and recurrent pregnancy failures.

19.
Lab Chip ; 19(24): 4104-4116, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31720646

RESUMO

Digital polymerase chain reaction (dPCR) is a powerful tool for genetic analysis, providing superior sensitivity and accuracy. In many applications that demand minuscule reaction volumes, such as single cell analysis, efficient and reproducible sample handling and digitization is pivotal for accurate absolute quantification of targets, but remains a significant technical challenge. In this paper, we described a robust and flexible microfluidic alternating-pull-push active digitization (µAPPAD) strategy that confers close to 100% sample digitization efficiency for microwell-based dPCR. Our strategy employs pneumatic valve control to periodically manipulate air pressure inside the chip to greatly facilitate the vacuum-driven partition of solution into microwells, enabling efficient digitization of a small-volume solution with significantly reduced volume variability. The µAPPAD method was evaluated on both tandem-channel and parallel-channel chips, which achieved a digitization efficiency of 99.5 ± 0.3% and 94.6 ± 0.9% within 10.5 min and 2 min, respectively. To assess the analytical performance of the µAPPAD chip, we calibrated it for absolution dPCR quantitation of λDNA across a range of concentrations. The results obtained with our chip matched well with the theoretical curve computed from Poisson statistics. Compared to the existing methods for highly efficient sample digitization, not only does our technology greatly reduce the constraints on microwell geometries and channel design, but also benefits from the intrinsic amenability of the pneumatic valve technique with device integration and automation. Thus we envision that the µAPPAD technology will provide a scalable and widely adaptable platform to promote the development of advanced lab-on-a-chip systems integrating microscale sample processing with dPCR for a broad scope of applications, such as single cell analysis of tumor heterogeneity and genetic profiling of circulating exosomes directly in clinical samples.

20.
Carcinogenesis ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31628462

RESUMO

Liver cancer and other malignant tumor cells rely on the glycolytic pathway to obtain energy (i.e., the Warburg effect); however, the underlying mechanism is unclear. Mitochondria are sites of oxidative phosphorylation and adenosine triphosphate (ATP) production. The 13 constituent respiratory chain proteins encoded by the mitochondrial genome (namely, mtDNA) play essential roles. We found that in human hepatocellular carcinoma (HCC) tissues, 11 of the 13 mtDNA-encoded genes exhibited decreased mRNA levels and 5 genes displayed decreased protein levels, including the cytochrome B (mt-CYB) and cytochrome C oxidase II (mt-CO2) genes. Mitochondrial gene sequencing revealed abnormalities in the levels of a large number of mitochondrial miRNAs (mitomiRs). MicroRNA-181a-5p (mir-181a-5p), which potentially targets genes encoding mt-CYB and mt-CO2 protein, was screened out from 549 downregulated mitomiRs via bioinformatic analysis. After overexpression of mitomiR-181a-5p, mt-CYB and mt-CO2 levels were reduced in HCC cells, and the mitochondrial membrane potential (MMP) maintained by the electron transport chain (ETC) was decreased. Furthermore, the expression of hexokinase 2 (HK2) and glucose transporter type 1 (GLUT1) was upregulated, accompanied by elevated glucose, lactic acid release, and activity of lactate dehydrogenase (LDH). In vivo experiments confirmed that constitutive mitomiR-181a-5p expression caused reprogramming of glucose metabolism and promoted tumor growth and early lung metastasis in liver cancer. In summary, the present study reveals the important role of mitomiRs in glucose metabolism reprogramming in liver cancer, which is of considerable value in exploring new therapeutic targets for HCC.

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