An inflammation-related gene landscape predicts prognosis and response to immunotherapy in virus-associated hepatocellular carcinoma.

Background: Due to the viral infection, chronic inflammation significantly increases the likelihood of hepatocellular carcinoma (HCC) development. Nevertheless, an inflammation-based signature aimed to predict the prognosis and therapeutic effect in virus-related HCC has rarely been established. Method: Based on the integrated analysis, inflammation-associated genes (IRGs) were systematically assessed. We comprehensively investigated the correlation between inflammation and transcriptional profiles, prognosis, and immune cell infiltration. Then, an inflammation-related risk model (IRM) to predict the overall survival (OS) and response to treatment for virus-related HCC patients was constructed and verified. Also, the potential association between IRGs and tumor microenvironment (TME) was investigated. Ultimately, hub genes were validated in plasma samples and cell lines via qRT-PCR. After transfection with shCCL20 combined with overSLC7A2, morphological change of SMMC7721 and huh7 cells was observed. Tumorigenicity model in nude mouse was established. Results: An inflammatory response-related gene signature model, containing MEP1A, CCL20, ADORA2B, TNFSF9, ICAM4, and SLC7A2, was constructed by conjoint analysis of least absolute shrinkage and selection operator (LASSO) Cox regression and gaussian finite mixture model (GMM). Besides, survival analysis attested that higher IRG scores were positively relevant to worse survival outcomes in virus-related HCC patients, which was testified by external validation cohorts (the ICGC cohort and GSE84337 dataset). Univariate and multivariate Cox regression analyses commonly proved that the IRG was an independent prognostic factor for virus-related HCC patients. Thus, a nomogram with clinical factors and IRG was also constructed to superiorly predict the prognosis of patients. Featured with microsatellite instability-high, mutation burden, and immune activation, lower IRG score verified a superior OS for sufferers. Additionally, IRG score was remarkedly correlated with the cancer stem cell index and drug susceptibility. The measurement of plasma samples further validated that CCL20 upexpression and SLC7A2 downexpression were positively related with virus-related HCC patients, which was in accord with the results in cell lines. Furthermore, CCL20 knockdown combined with SLC7A2 overexpression availably weakened the tumor growth in vivo. Conclusions: Collectively, IRG score, serving as a potential candidate, accurately and stably predicted the prognosis and response to immunotherapy in virus-related HCC patients, which could guide individualized treatment decision-making for the sufferers.

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence-Free Survival in Hepatocellular Carcinoma.

Background: Current research studies have suggested that glucose deprivation (GD)-based tumor microenvironment (TME) can promote epithelial-mesenchymal transition (EMT) of tumor cells, leading to tumor invasion and metastasis. However, no one has yet studied detailedly the synthetic studies that include GD features in TME with EMT status. In our research, we comprehensively developed and validated a robust signature regarding GD and EMT status to provide prognostic value for patients with liver cancer. Methods: GD and EMT status were estimated with transcriptomic profiles based on WGCNA and t-SNE algorithms. Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses. We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse. Results: Patients with significant GD-EMT status were divided into two subgroups: GDlow/EMTlow and GDhigh/EMThigh, with the latter having significantly worse recurrence-free survival (P < 0.01). We employed the least absolute shrinkage and selection operator (LASSO) technique as a method for HNF4A and SLC2A4 filtering and constructing a risk score for risk stratification. In the multivariate analysis, this risk score predicted recurrence-free survival (RFS) in both the discovery and validation cohorts and remained valid in patients stratified by TNM stage and age at diagnosis. The nomogram that combines risk score and TNM stage as well as age produces improved performance and net benefits in the analysis of calibration and decision curves in training and validation groups. Conclusions: The GD-EMT-based signature predictive model may provide a prognosis classifier for HCC patients with a high risk of postoperative recurrence to decrease the relapse rate.

[Intervention effect of Jingfang Mixture on urticaria mice based on NF-κB/NLRP3/IL-1ß signaling pathway].

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.

[Anti-inflammatory mechanism of active ingredients in Jingfang Mixture based on network pharmacology and experimental verification].

The present study aimed to explore the regulatory targets and anti-inflammatory mechanism of Jingfang Mixture based on network pharmacology and animal tests. The active ingredients of Jingfang Mixture and the corresponding targets were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Inflammation-related targets were searched from GeneCards and DisGeNET, and the targets of active ingredients of Jingfang Mixture against inflammation were obtained. The protein-protein interaction(PPI) network was analyzed by STRING and plotted. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out based on DAVID. The results of network pharmacology showed 159 active ingredients and 276 targets of Jingfang Mixture and 664 inflammation-related targets were screened out, and 90 targets of active ingredients of Jingfang Mixture against inflammation were obtained. As revealed by the PPI network, protein kinase B1(AKT1), caspase-3(CASP3), interleukin-1ß(IL1 B), prostaglandin-endoperoxide synthase 2(PTGS2), and tumor necrosis factor(TNF) might be the key proteins for the anti-inflammatory effect of Jingfang Mixture. KEGG enrichment analysis demonstrated the pathways involved TNF, nuclear factor-kappa B(NF-κB), and mitogen-activated protein kinase(MAPK). The anti-inflammatory effect of Jingfang Mixture was explored through the mouse model of urticaria. The results indicated that Jingfang Mixture could down-regulate the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases(ERK1/2), and NF-κB. The present study revealed the anti-inflammatory effect of Jingfang Mixture with multi-component and multi-target characteristics, which is expected to provide a scientific basis and important support for further research, development, and application.

[Proteomic study of Jingfang Mixture on urticaria based on label-free quantitative proteomics technology].

This study aims to explore the effect of Jingfang Mixture on the protein expression of urticaria in mice and explain the mechanism of Jingfang Mixture in the treatment of urticaria. Twenty-seven male Kunming mice were randomly divided into a normal group, a model group and a Jingfang Mixture group according to body weight. Except for the normal group, mice in the model group and the Jingfang Mixture group were injected with the mixture of ovalbumin and Al(OH)_3 gel for the first immunization, and the second immunization was performed on the 10 th day to induce the urticaria model. Mice in the Jingfang Mixture group started to be administered on the 6 th day after the initial immunization, and was administered continuously for 21 days. The normal group and the model group were replaced with the same amount of purified water. Twenty-four hours after the last administration, an appropriate amount of skin was taken, and label-free quantitative proteomics technology was used to detect the differences in protein expression in skin tissue. The signaling pathways involved in the differential proteins was further analyzed. The results of proteomics indicated that seventy-six proteins were involved in the intervention of Jingfang Mixture on mice with urticaria, and the differential proteins were mainly enriched in biological process(BP), molecular function(MF), and cellular component(CC). Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the signaling pathways regulated by Jingfang Mixture mainly involved carbon metabolism, metabolic pathways, glucagon signaling pathway, glycolysis/gluconeogenesis, pentose phosphate pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, purine metabolism, adherens junction, calcium signaling pathway, leukocyte transendothelial migration, and inflammatory mediator regulation of transient receptor potential(TRP) channels, which were involved in skin tissue energy metabolism and immune regulation. The findings of this study showed that the protective effect of Jingfang Mixture on mice with urticaria was closely related to the regulation of immune disorders, and the regulatory effect on immune system may be achieved through the regulation of energy metabolism by Jingfang Mixture.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.

[Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway].

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1ß, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Integrating Genomic and Transcriptomic Data to Reveal Genetic Mechanisms Underlying Piao Chicken Rumpless Trait.

Piao chicken, a rare Chinese native poultry breed, lacks primary tail structures, such as pygostyle, caudal vertebra, uropygial gland, and tail feathers. So far, the molecular mechanisms underlying tail absence in this breed remain unclear. In this study, we comprehensively employed comparative transcriptomic and genomic analyses to unravel potential genetic underpinnings of rumplessness in Piao chicken. Our results reveal many biological factors involved in tail development and several genomic regions under strong positive selection in this breed. These regions contain candidate genes associated with rumplessness, including Irx4, Il18, Hspb2, and Cryab. Retrieval of quantitative trait loci (QTL) and gene functions implies that rumplessness might be consciously or unconsciously selected along with the high-yield traits in Piao chicken. We hypothesize that strong selection pressures on regulatory elements might lead to changes in gene activity in mesenchymal stem cells of the tail bud. The ectopic activity could eventually result in tail truncation by impeding differentiation and proliferation of the stem cells. Our study provides fundamental insights into early initiation and genetic basis of the rumpless phenotype in Piao chicken.

LncRNA RPPH1 attenuates Aß25-35-induced endoplasmic reticulum stress and apoptosis in SH-SY5Y cells via miR-326/PKM2.

BACKGROUND: The durative endoplasmic reticulum stress (ERS) and subsequent apoptosis contributes to the development and progression of Alzheimer's disease (AD). MiR-326 can reduce pyruvate kinase M2 (PKM2) expression, leading to ERS. Whereas, lncRNA RPPH1 is able to increase dendritic spine density and protect hippocampal pyramidal neurons through targeting miR-326. Our study aims to investigate the regulation of lncRNA RPPH1 and miR-326/PKM2 on ERS and related apoptosis in AD. METHODS: SH-SY5Y cells treated with Aß25-35 were selected as an in vitro AD model. RPPH1 and miR-326 overexpression and silencing cells were established by transforming vectors. The expression of RPPH1 and miR-326 were detected by qRT-PCR. MTT, flow cytometric, intracellular calcium assay and Western blot were used to test the functions of RPPH1 and miR-326 in SH-SY5Y cell proliferation, apoptosis and ERS. Dual-luciferase assay was used to detect the interaction among RPPH1, miR-326 and PKM2. RESULTS: RPPH1 overexpression enhanced the viability of SH-SY5Y cells, and attenuated the apoptosis of of SH-SY5Y cells. Moreover, RPPH1 overexpression down-regulated ER stress related proteins such as GRP78, CHOP and cleaved caspase-12. Mechanistically, RPPH1 directly targeted miR-326, thereby counteracting its inhibitory effect on PKM2 expression, contributing to attenuation of apoptosis and ERS induced by Aß25-35. CONCLUSION: Aß25-35-induced ERS and apoptosis in SH-SY5Y cells can be attenuated by lncRNA RPPH1 through regulating miR-326/PKM2 axis. This study provided therapeutic options for AD patients.

Expression and significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in biopsy specimen of squamous cell carcinoma, adenocarcinoma and small cell lung carcinoma / Expresión y significado de CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56 Syn y CgA en muestras de biopsia de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas de pulmón

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer.

Se midieron tumores y utilizaron nueve biomarcadores potenciales y se analizó la información para diagnosticar la enfermedad. A todos los pacientes se les realizó citología en líquido con broncoscopía de fibra y examen histopatológico para detectar de manera confiable el cáncer pulmonar. Se obtuvieron muestras de 314 pacientes chinos con cáncer de pulmón y CK5 / 6, P63, P40, CK7, TTF-1, Napsina A, CD56, Syn y CgA se midieron a través de histoquímica SP y analizaron la correlación de la expresión de estos marcadores con características patológicas y clínicas de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas en el cáncer de pulmón. El carcinoma de células escamosas, el adenocarcinoma y el carcinoma de células pequeñas fueron 61 casos, 114 casos y 139 casos, respectivamente, la expresión de CK5 / 6 y P63 fueron más frecuentes en el carcinoma de células escamosas, con una sensibilidad y especificidad del 77,05 % y 96,44 %, 83,61 % y 88,93 %, y en comparación con el adenocarcinoma y el carcinoma de células pequeñas, la diferencia fue estadísticamente significativa (P <0,05). La incidencia de ap la expresión positiva P40 fue del 100 % en el carcinoma de células escamosas, con una especificidad del 98,81 %. La expresión de CK7, TTF-1 y NapsinA fueron más frecuentes en el adenocarcinoma, con una sensibilidad y especificidad del 85,09 % y 78,69 %, 79,82 % y 93,44 %, 56,14 % y 95,08 %, y en comparación con el carcinoma de células escamosas y la diferencia de carcinoma de células pequeñas fue estadísticamente significativa (P <0,05) .TTF-1, Syn, CgA y la expresión de CD56 fueron más frecuentes en adenocarcinoma, con sensibilidad y especificidad de 86.33 % y 93.44 %, 89.21 % y 98.36 %, 74.10 % y 100 %, 96.40 % y 96.72 %. La detección combinada de CK5 / 6, P63 y P40 fue más útil y específica en la diferenciación del carcinoma de células escamosas. CK7, TTF-1 y NapsinA fueron más útiles y específicos para diferenciar el adenocarcinoma de pulmón. El deterioro de CD56, TTF-1, Syn y CgA refleja la progresión del cáncer de pulmón de células pequeñas.

LncRNA Rpph1 protects amyloid-ß induced neuronal injury in SK-N-SH cells via miR-122/Wnt1 axis.

Objective: To investigate the role of lncRNA Rpph1 on amyloid-ß induced neuronal injury in SK-N-SH cells and underlying mechanism.Methods: In vitro Alzheimer's disease (AD) model was established using the SK-N-SH cells treated with Aß25-35 peptide. APPswe/PS1ΔE9 double transgenic mice were used as AD animal model. Rpph1 was over-expressed and miR-122 was inhibited or overexpressed in SK-N-SH cells via transfection with pcDNA3.1-oe Rpph1 vector, miR-122 inhibitor or miR-122 mimic, respectively. Cell viabilities and apoptosis were evaluated using MTT or flow cytometry assay, respectively. Quantitative real-time PCR (RT-qPCR) was used to determine expression of Rpph1 and miR-122. Western blotting was used to determine the expression of apoptosis related proteins as well as Wnt/ß-catenin signaling related proteins. Dual luciferase reporter assay was conducted to confirm the binding of miR-122 with predictive binding site in 3' UTR of Rpph1 and Wnt1.Results: Both lncRNA Rpph1 and miR-122 were up-regulated in AD mouse. Either over-expression of Rpph1 or inhibition of miR-122 restored the cell viability or decreased cell apoptosis rate in Aß induced SK-N-SH cells. Overexpression of miR-122 inhibited the cell viability while did not influence the Aß level in SK-N-SH cells. Furthermore, over-expression of Rpph1, as well as inhibition of miR-122, elevated Bcl-2, c-myc, Survivin and decreased Bax expression via activating Wnt/ß-catenin signaling. Dual luciferase reporter assay showed that miR-122 could directly target to 3'UTR of Rpph1 and Wnt1.Conclusion: Both lncRNA Rpph1 and miR-122 were up-regulated in AD mouse and Rpph1 activated Wnt/ß-catenin signaling to ameliorate amyloid-ß induced neuronal apoptosis in SK-N-SH cells via direct targeting miR-122.

miR-148a suppresses autophagy by down-regulation of IL-6/STAT3 signaling in cerulein-induced acute pancreatitis.

Acute pancreatitis (AP) is a type of sterile inflammation of the pancreas, potentially leading to systemic inflammatory response syndrome or multiple organ failure. An emerging evidence that dysfunction of miRNA expression may alter pivotal physiological functions and lead to inflammation infiltration and complication of multiple diseases, including AP. Here, the AP model was successfully replicated using cerulein in vitro and in vivo. RT-qPCR was used to detect low expression of miR-148a in AP. This study verified that IL-6 was a direct target of miR-148a. Over-expression of miR-148a decreased the mRNA and protein levels of IL-6 by RT-qPCR and Elisa. Moreover, over-expression of miR-148a improved the pathological state of AP through H&E and MPO staining and transmission electron microscopy. After over-expressing miR-148a, Western blot and immunohistochemical method were used to confirm the reduction of autophagosomes and autolysosomes, blockade of the levels of p-STAT3, LC3-II, ATG7, ATG4c, Beclin1 and the increased p62 expression in AP. The expression of LAMP-2 was not significantly different. In addition, IL-6 and AG490, the IL-6/STAT3 signaling inhibitor, were used to verify the role of IL-6/STAT3 signaling in the regulation of miR-148a on autophagy in cerulein-induced AP in vitro and in vivo. Taken together, our findings indicate that miR-148a suppresses autophagy via regulating IL-6/STAT3 signaling in cerulein-induced AP in vitro and in vivo. The miR-148a appears to be a promising candidate for the gene therapy of AP.

Isocostunolide inhibited glioma stem cell by suppression proliferation and inducing caspase dependent apoptosis.

Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored. In this investigation, the anti-tumor activity of isocostunolide against GSCs was investigated and the result demonstrated that it inhibited the growth of GSCs (GSC-3#, GSC-12#, GSC-18#) significantly with an IC50 value of 2.80µg/ml, 2.61µg/ml, 1.07µg/ml, respectively. In further mechanism study, isocostunolide inhibited GSCs cell proliferation, induced GSCs apoptosis significantly, as well as increased the proportion of the cleavage of caspase-3. The result suggested that isocostunolide induced GSCs apoptosis via the caspase dependent apoptotic pathway. Moreover, isocostunolide damaged GSCs colony formation capacity significantly and exhibited the anti-cancer efficacy against GSCs in vitro.

Preparation and Microwave Absorption Properties of Novel Carbon Nanofiber/Fe3O4 Composites.

Novel, carbonized bacterial cellulose (CBC)/Fe3O4 nanocomposites were synthesized using vacuum filtration and annealing (VFA) methods. The as-synthesized products were characterized by scanning electron microscopy, vibrating sample magnetometry, and transmission electron microscopy. The complex permittivity and permeability of Fe3O4-CBC (5 wt.% CBC)/paraffin wax composites were measured by vector network analysis. To study the microwave absorption (MA) performances, we compared the VFA products with the vacuum filtration (VF) products. The VFA products exhibited better absorption performances because of their larger dielectric loss. When the matching thickness was 2.4 mm, the calculated reflection loss reached a minimum value of -27 dB when VFA was used and a value of -11 dB when VF was used. The wide-range MA properties of these materials lead to potential applications in MA fields.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

BACKGROUND: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. MATERIALS AND METHODS: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. RESULTS: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. CONCLUSIONS: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Treatment for displacement of PAAG mixture after injection augmentation mammoplasty.

BACKGROUND: The incidence of serious complications after augmentation mammaplasty with injection of polyacrylamide hydrogel (PAAG) was high. OBJECTIVE: To design a new method for healing of the cavities and cysts after augmentation mammaplasty. METHODS: 102 patients in whom PAAG exceeded the breast and spread to the thoracic-abdominal walls were enrolled and divided into two groups. RESULTS: The flowing masses of different sizes exceeded the breast and spread to the thoracic-abdominal walls, and a large number of PAAG showed flowing degenerative mixture in the tissues and were invaded by many inflammatory cells. PAAG deposited extensively in the breast tissues, armpits and space of the thoracic-abdominal wall, and the breast was connected with the abdominal wall through the fistula of different sizes. At 2 weeks, the percentages of decrease in drainage volume and in lesion lacuna size of the thoracic-abdominal wall (82% and 80%, respectively) in patients receiving the multiple incisions combined with radical therapy were significantly different from those who did not receive the multiple incisions (46% and 45%) (Both P<0.01). At 4 weeks, in some of the patients receiving the multiple incisions combined with radical therapy, the lacuna of the thoracic-abdominal wall disappeared completely, and the lesions with flowing masses had been cleared. CONCLUSIONS: The new method of subareolar incision combined with surgery for inferior segment of mass to clean the mixture and thoroughly eliminate the lacuna of the thoracic-abdominal wall as well as suture to close the intramammary fistula can improve the treatment efficacy.

Comparison of Artecoll, Restylane and silicone for augmentation rhinoplasty in 378 Chinese patients.

PURPOSE: Dermal fillers have been proven to be safe in soft tissue augmentation; however, their efficacy in modeling the noses of Asian patients has not been demonstrated. METHODS: In this study, 378 patients were included and underwent augmentation rhinoplasty (Artecoll, n=126; Restylane, n=126 and silicone implants, n=126). The subjective and objective outcomes were evaluated on day 1, and months 1, 3, 6, and 12 after injection rhinoplasty. RESULTS: All patients achieved significant improvement in nasal shape and contour immediately after surgery. Patients treated with Restylane failed to maintain the nasal shape and contour 1 year after surgery, whereas patients undergoing Artecoll rhinoplasty completely maintained the post-treatment nasal shape and contour. More patients with silicone implants experienced adverse events and the severity of these events was greater in the silicone group compared to those in the Restylane and Acetoll groups. CONCLUSION: Artecoll rhinoplasty has a low incidence of adverse effects and the shape and contour of the nose are maintained for a prolonged period.

Safety and efficacy of a novel disposable sheathed gastroscopic system in clinical practice.

BACKGROUND AND AIM: Endoscopic examinations carry a potential risk of cross-infection, and the traditional reprocessing method is time consuming. We evaluated the safety and efficacy of a novel disposable sheathed gastroscope system in clinical practice in comparison with the conventional gastroscope. METHODS: There were two phases in the study. In phase 1, 20 patients with hepatitis B were randomized into two groups: the sheathed group was examined with the novel disposable sheathed gastroscope (n = 10) and the conventional group with the conventional gastroscope (n = 10). Microbiologic tests were performed on each endoscope afterwards. In the second phase, 1120 patients were randomized again into the same two groups with 568 and 552 patients in the sheathed group and the conventional group, respectively. The time duration of the endoscopic procedure and reprocessing were measured. The pathology detection rate of endoscopic examinations, the patients' subjective feelings, and problems occurred during procedures were also recorded. RESULTS: The total instrument turn-around time in the phase 2 sheathed group (9.9 ± 1.3 min) was significantly shorter than the conventional group (39.0 ± 1.4 min, P = 0.000). The mean procedural time was slightly longer in the sheathed group than in the conventional group (4.9 ± 1.4 vs 4.1 ± 1.3 min, P = 0.000). However, the duration of endoscopic reprocessing was much shorter (4.9 ± 0.2 vs 35 ± 0.2 min, P = 0.000). No significant differences were observed in patient discomfort, optical clarity, or pathology detection rate. There were no complications in either group, and no microbial contamination was detected in phase 1 of the study. CONCLUSIONS: Compared with the conventional gastroscope, the novel disposable sheathed gastroendoscope is safe and more efficient in clinical practice.