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2.
Artigo em Inglês | MEDLINE | ID: mdl-34798935

RESUMO

In the present study, the suitability and sensitivity of different in vitro toxicity endpoints were determined to evaluate and distinguish the specific contributions of polycyclic aromatic carbon (PAC) mixtures from various sites in Toronto (Canada), to pulmonary toxicity. Air samples were collected for two-month periods from April 2014 to March 2015 from one location, and from August 2016 to August 2017 from multiple locations reflecting different geographical areas in Toronto, and the Greater Toronto Area, with varying source emissions including background, traffic, urban, industrial and residential sites. Relative concentrations of PACs and their derivatives in these air samples were characterised. In vitro cytotoxicity, pro-inflammatory, and oxidative stress assays were employed to assess the acute pulmonary effects of urban-air-derived air pollutants. In addition, global transcriptional profiling was utilized to understand how these chemical mixtures exert their harmful effects. Lastly, the transcriptomic data and the chemical profiles for each site and season were used to relate the biological response back to individual constituents. Site-specific responses could not be derived; however, the Spring season was identified as the most responsive through benchmark concentration analysis. A combination of correlational analysis and principal component analysis revealed that nitrated and oxygenated polycyclic aromatic hydrocarbons (PAHs) drive the response at lower concentrations while specific PAHs drive the response at the highest concentration tested. Unsubstituted PAHs are the current targets for analysis as priority pollutants. The present study highlights the importance of by-products of PAH degradation in the assessment of risk. The study also demonstrates the usefulness of in vitro toxicity assays to derive meaningful data in support of risk assessment.

3.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1492-1500, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755664

RESUMO

OBJECTIVE: To investigate the characteristics of immune cell subsets in the lung tissues of patients with chronic obstructive pulmonary disease (COPD) and the mechanism of Liuwei Buqi capsule in modulating immune and inflammatory imbalance in COPD. METHODS: We downloaded COPD-related single-cell RNA sequencing data from Gene Expression Omnibus (GEO) and identified COPD immune cell subsets using the Seurat package in the R software to construct an immune cell subsets-differential genes network. The target genes and active ingredients of Liuwei Buqi capsule were obtained from the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the Liuwei Buqi capsule-immune cell subsets-target genes network was constructed by mapping the target genes to the differentially expressed genes in each immune cell subset. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to analyze significantly enriched pathways of the target genes, and the key genes involved in the top 20 pathways were identified. In a rat model of COPD, we investigated the effects of Liuwei Buqi capsule on pulmonary function, lung tissue pathology, serum levels of IL-1ß, NF-κB, and TNF-α, and expressions of IKBα, JNK, c-JUN, and c-FOS proteins in the lung tissue. RESULTS: A total of 18 immune-related cell subsets, including macrophages and alveolar macrophages, were identified in both COPD patients and healthy control subjects, and the patients with COPD showed significant changes the percentages of macrophages, cDC1, pDC, mast cells, T cells, and mature dendritic cells (P < 0.05). Liuwei Buqi capsules targeted multiple immune cell subsets, and the identified target genes were enriched mostly in such immune and inflammation-related signaling pathways as lipids and atherosclerosis, IL-17 signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway; the genes CXCL8, IL1B, JUN, NFKBIA, MAPK8, and FOS were the key genes involved in the significantly enriched pathways. In the rat models of COPD, treatment with Liuwei Buqi capsule significantly improved pulmonary function, alleviated lung pathologies, reduced serum levels of IL-1ß, TNF-α, and NF-κB (P < 0.05) and pulmonary expressions of JNK, c-JUN, and c-FOS (P < 0.01) protein, and increased pulmonary expression of IκBα (P < 0.01). CONCLUSION: Liuwei Buqi capsule may play an immunomodulatory role by targeting multiple immune cell subsets in the lung tissue of COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Imunidade , Pulmão/metabolismo , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Transdução de Sinais
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1509-1518, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755666

RESUMO

OBJECTIVE: To identify the key genes involved in the transformation of hepatitis B virus (HBV) into hepatocellular carcinoma (HCC) and explore the underlying molecular mechanisms. METHODS: We analyzed the mRNA microarray data of 119 HBV-related HCC tissues and 252 HBV-related non-tumor tissues in GSE55092, GSE84044 and GSE121248 from the GEO database, and the "sva" R package was used to remove the batch effects. Integration analysis was performed to identify the differentially expressed genes (DEGs) in HBV-related liver cancer and liver tissues with HBV infection. The significant DEGs were functionally annotated using GO and KEGG analyses, and the most important modules and hub genes were explored with STRING analysis. Kaplan-Meier and Oncomine databases were used to verify the HCC gene expression data in the TCGA database to explore the correlations of the hub genes with the occurrence, progression and prognosis of HCC. We also examined the expressions of the hub genes in 17 pairs of surgical specimens of HCC and adjacent tissues using RT-qPCR. RESULTS: We identified a total of 121 DEGs and 3 genetic markers in HCC (P < 0.01). These DEGs included cyclin1 (CDK1), cyclin B1 (CCNB1), and nuclear division cycle 80 (NDC80), which participated in cell cycle, pyrimidine metabolism and DNA replication and were highly correlated (P < 0.05). Analysis of the UALCAN database confirmed high expressions of these 3 genes in HCC tissues, which were correlated with a low survival rate of the patients, as shown by Kaplan-Meier analysis of the prognostic data from the UALCAN database. CDK1, CCNB1 and NDC80 were all correlated with the clinical grading of HCC (P < 0.05). The results of RT-qPCR on the surgical specimens verified significantly higher expressions of CDK1, CCNB1 and NDC80 mRNA in HCC tissues than in the adjacent tissues. CONCLUSION: CDK1, CCNB1 and NDC80 genes can be used as prognostic markers of HBV-related HCC and may serve as potential targets in preclinical studies and clinical treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteína Quinase CDC2/genética , Carcinoma Hepatocelular/genética , Divisão do Núcleo Celular , Biologia Computacional , Ciclina B1/genética , Proteínas do Citoesqueleto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/genética , Prognóstico
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(5): 891-897, 2021 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814484

RESUMO

Objective: To isolate the influenza A (H3N2) viruses from different sources in Guangzhou in 2019 and analyze these viruses' evolution and variation characteristics. Methods: The hemagglutinin (HA) and neuraminidase (NA) genes of H3N2 isolates from outpatient monitoring, influenza outbreaks, and inpatient severe cases in Guangzhou in 2019 were sequenced. Bioinformatics software analyzed the variations and evolution characteristics of HA and NA genes. Results: The epidemic peaks of influenza A (H3N2) viruses were made up of period Ⅰ (from January to August) and period Ⅱ (from November to December). The positive rate of influenza A (H3N2) in males was 13.46% (703/5 221), which was higher than that in females (11.50%, 510/4 435) (χ2=8.43,P=0.00). The group's positive rate of 10-20 years old was the highest (25.18%,665/2 641). The isolates from different sources were highly homologous and closely related to 3C.2a.1 branches, which could be further divided into three small groups of Group 1-3. Gene recombination was observed between different branches. The mutations of HA antigen sites gradually appeared from Group 1 to Group 3, leading to new antigen drift. Variations of HA antigenic sites mainly occurred in the region of A and B. The mutations of receptor binding sites of Group 1 and Group 3 viruses occurred in the anterior and posterior walls. There were two glycosylation sites lacked on region A of HA antigen observed in the isolates of Group 2-3. Conclusions: Genetic variations of H3N2 influenza viruses in Guangzhou included gene mutations and gene recombination. Under the pressure of the vaccine, the evolution of viruses was rapid. Therefore, the monitoring of molecular-related epidemic characteristics of the H3N2 influenza virus was necessary.


Assuntos
Epidemias , Vírus da Influenza A , Influenza Humana , Adolescente , Adulto , Criança , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Masculino , Neuraminidase/genética , Filogenia , Adulto Jovem
6.
Clin Radiol ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34756699

RESUMO

AIM: To evaluate the accuracy of the lesion-to-erector spinae signal intensity ratio (SIR) on magnetic resonance imaging (MRI) for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: The MRI data of 21 patients with AIP and 27 patients with PDA were analysed retrospectively, and the signal intensity in pancreatic lesions and erector spinae muscles at the same level on T2-weighted imaging (T2WI), arterial phase (AP) imaging, and delayed phase (DP) imaging was measured for calculation of SIRs. RESULTS: The mean SIRs of the pancreatic lesions and erector spinae from T2WI, AP, and DP images of AIP patients were 0.96, 1.27, and 1.42, respectively, while those of PDA patients were 1.35, 0.80, and 0.91, respectively. The differences in the SIRs between the AIP and PDA groups were statistically significant (p<0.001), with corresponding area under curve (AUC) values of 0.925, 0.906, and 0.961, respectively. The optimal cut-off values for the SIRs on T2WI, AP and DP images were 1.21, 1.01, and 1.08, respectively. SIR values < 1.21 on T2WI, >1.01 on AP imaging, and >1.08 on DP imaging identified AIP with sensitivities of 85.7%, 90.5%, and 90.5%, respectively, and specificities of 81.5%, 74.6%, and 81.5%, respectively. The AUC values for SIRs did not differ significantly between T2WI and DP imaging or AP and DP imaging (Z = 0.778, p=0.436; Z = 1.279, p=0.201). CONCLUSION: The SIRs of pancreatic lesions and erector spinae on T2WI, AP, and DP images can be used to differentiate AIP from PDA.

7.
J Dent Res ; : 220345211044681, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719965

RESUMO

Periodontitis is a chronic inflammatory condition characterized by destruction of nonmineralized and mineralized connective tissues. This study evaluated the role of Trem1 (triggering receptors expressed on myeloid cells 1) in periodontitis by influencing polarization of M1 macrophages through the STAT3/HIF-1α signaling pathway. Trem1 was significantly upregulated in the gingival tissues of patients with periodontitis, as identified by high-throughput RNA sequencing, and positively correlated with levels of M1 macrophage-associated genes. The results of flow cytometry, Western blotting, and reverse transcription quantitative polymerase chain reaction showed that knockdown of Trem1 in RAW 264.7 cells decreased polarization of M1 macrophages and increased polarization of M2 macrophages, while overexpression of Trem1 exerted an opposite effect. Furthermore, a mouse model of Trem1 knockout periodontitis exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in periodontitis lesions and bone marrow-derived macrophages. Importantly, we found that Trem1 could regulate polarization of M1 macrophages through STAT3/HIF-1α signaling as evidenced by RNA sequencing. Moreover, inhibition of Trem1 and HIF-1α could suppress the expression level of proinflammatory cytokine (interleukin 1ß) and upregulate the expression level of anti-inflammatory cytokine (interleukin 10) in periodontitis. Collectively, we identified that the Trem1/STAT3/HIF-1α axis could regulate polarization of M1 macrophages and is a potential candidate in the treatment of periodontitis.

8.
Zhonghua Er Ke Za Zhi ; 60: 1065-1073, 2021 Dec 02.
Artigo em Chinês | MEDLINE | ID: mdl-34839591

RESUMO

Objective: To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight. Methods: A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results: The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion: The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

9.
Zhonghua Shao Shang Za Zhi ; 37: 1-10, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34839600

RESUMO

Objective: To investigate the effects and cell signaling mechanism of glutamine on rat cardiomyocytes intervened with serum from burned rat (hereinafter referred to as burn serum). Methods: The experimental research method was applied. Ten gender equally distributed Wistar rats aged 7-8 months were taken to prepare normal rat serum (hereinafter referred to as normal serum), another twenty gender equally distributed Wistar rats aged 7-8 months were taken to prepare burn serum after full- thickness burn injury of 30% total body surface area, and cardiomyocytes were isolated from 180 Wistar rats aged 1-3 days by either gender and used in the following experiments. The cells were divided into normal serum group and burn serum group according to the random number table (the same grouping method below), and cultured with the corresponding serum. At post culture hour (PCH) 1, 3, 6, 9, and 12, trypanosoma blue exclusion test was used to detect the cell survival rate. The cells were divided into burn serum alone group, burn serum+4 mmol/L glutamine group, burn serum+8 mmol/L glutamine group, burn serum+12 mmol/L glutamine group, burn serum+16 mmol/L glutamine group, and burn serum+20 mmol/L glutamine group, and were treated with burn serum alone or added with the corresponding final molarity of glutamine and cultured with the time point screened in the experiment before, then the cell survival rate was dected as before. then The cells were divided into normal serum alone group, burn serum alone group, burn serum+12 mmol/L glutamine group, burn serum+16 mmol/L glutamine group, and burn serum+20 mmol/L glutamine group and treated the same as before. After 30 min of culture, phosphorylation level of mammalian target of rapamycin complex 1 (mTORC1), p70 ribosomal protein S6 kinase (P70 S6k), and eIF4E-binding protein 1 (4E-BP1) were detected by Western blotting. Cells were divided into normal serum group, burn serum alone group, burn serum+12 mmol/L glutamine group, burn serum+12 mmol/L glutamine+25 ng/mL rapamycin group, and treated correspondingly. At PCH 1, 3, and 6, the expressions of heat shock protein 70 (HSP70) and metallothionein (MT), and the morphology of microtubule were observed with immunofluorescence method. The number samples in each index at each time point in each group were all 10. Data were statistically analyzed with analysis of variance of factorial design, one-way analysis of variance, least significant difference t test, least significant difference test, and Bonferroni correction. Results: At PCH 1, 3, 6, 9, and 12, the cell survival rates in burn serum group were significantly lower than those in normal serum group (t=4.950, 16.752, 35.484, 34.428, 27.781, P<0.01). Compared within group at PCH 1, the cell survival rate was significantly decreased in burn serum group at PCH 3, 6, 9, and 12 (P<0.05). Compared within group at PCH 3, the cell survival rate was significantly decreased in burn serum group at PCH 6, 9, and 12 (P<0.05). Compared within group at PCH 6 and 9, the cell survival rate was significantly decreased in burn serum group at PCH 12 (P<0.05). There were no statistically significant differences in the cell survival rate among burn serum group at PCH 6 and 9 (P>0.05). Thus PCH 6 was selected as the subsequent intervention time of burn serum. At PCH 6, compared with burn serum alone group, the cell survival rates in burn serum+4 mmol/L glutamine group, burn serum+8 mmol/L glutamine group, burn serum+12 mmol/L glutamine group, burn serum+16 mmol/L glutamine group, and burn serum+20 mmol/L glutamine group were significantly increased (P<0.01). There were no statistically significantl differences in cell survival rate in burn serum+12 mmol/L glutamine group and burn serum+16 mmol/L glutamine group (P>0.05). There were no statistically significantl differences in cell survival rate in burn serum+16 mmol/L glutamine group and burn serum+20 mmol/L glutamine group (P>0.05). Thus 12, 16, and 20 mmol/L were selected as the subsequent intervention concentrations of glutamine. After 30 min of culture, the phosphorylation levels of mTORC1, P70 S6k, and 4E-BP1 of cells were respectively 1.001±0.042, 0.510±0.024, 0.876±0.022, 0.836±0.074, 0.856±0.041, 1.00±0.11, 0.38±0.09, 0.95±0.13, 0.96±0.13, 0.89±0.24, 1.00±0.07, 0.29±0.08, 0.87±0.27, 0.68±0.08, 0.60±0.21 in normal serum group, burn serum alone group, burn serum+12 mmol/L glutamine group, burn serum+16 mmol/L glutamine group, and burn serum+20 mmol/L glutamine group. Compared with normal serum group, the phosphorylation levels of mTORC1, P70 S6k, and 4E-BP1 of cells were decreased in the other 4 groups (P<0.01). Compared with burn serum alone group, the phosphorylation levels of mTORC1, P70 S6k, and 4E-BP1 of cells were increased in the other 3 groups (P<0.01). The phosphorylation levels of mTORC1, P70 S6k, and 4E-BP1 of cells were similar in burn serum+12 mmol/L glutamine group, burn serum+16 mmol/L glutamine group, and burn serum+20 mmol/L glutamine group (P>0.05). The phosphorylation level of 4E-BP1 of cells in burn serum+12 mmol/L glutamine group was significantly higher than the levels in burn serum+16 mmol/L glutamine group and burn serum+20 mmol/L glutamine group (P<0.05). At PCH 1, 3, and 6, the expressions of HSP70 and MT of cells in burn serum alone group were significantly higher than those in normal serum group (P<0.01); the protein expressions of HSP70 and MT of cells in burn serum+12 mmol/L glutamine group were significantly higher than those in burn serum alone group (P<0.05); the protein expressions of HSP70 and MT of cells in burn serum+12 mmol/L glutamine+25 ng/mL rapamycin group were significantly lower than those in burn serum+12 mmol/L glutamine group (P<0.05). The microtubular structure was integral, network alinement, stain uniformity in normal serum group at PCH 1, 3, and 6. In burn serum alone group, some microtubules were broken and the grid arrangement was disordered at PCH 1; the microtubule structure near the nucleus was clear, while the microtubule at the distal end of the nucleus was blurred at PCH 3; the microtubule structure was blurred at PCH 6. The microtubular damage of cells was alleviated in burn serum+12 mmol/L glutamine group compared with burn serum alone group. The morphology of microtubule of cells in burn serum+12 mmol/L glutamine+25 ng/mL rapamycin group at each time point was similar to that of burn serum alone group. Conclusions: The burn serum can lead to cardiomyocyte damage and cell survival rate decrease in mice. Glutamine can exert cell protective function through regulating the mTOR-P70 S6k-4E-BP1 signaling pathway, thus promoting the expressions of HSP70 and MT and stabilize the microtubule structure.

10.
Rev Sci Instrum ; 92(9): 093901, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598515

RESUMO

We propose a novel micro-tensile system fit for mechanical property characterization of low-dimensional materials. The micro-tensile system was integrated with a micro-tensile apparatus driven by a piezoelectric transducer (PZT) and an optical microscope. The displacement provided by the PZT actuator was amplified by a lever structure on the micro-tensile apparatus. A stalloy was designed to transmit the displacement and reduce the mechanical resistance to the PZT actuator. Quantitative analysis was conducted for the designed apparatus. A calibration experiment was performed based on the micro-scale digital image correlation under the optical microscope. To validate the feasibility, the PET film specimen with a V-notch was tested by the proposed system. The results indicate that the proposed micro-tensile system is reliable and powerful.

12.
Zhonghua Shao Shang Za Zhi ; 37(9): 811-820, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34645146

RESUMO

Objective: To establish an efficient human intestinal trefoil factor (ITF) recombinant expression and purification strategy and to observe the effect of recombinant human ITF (rhITF) on intestinal mucosal injury and repair in burned rats and to explore the mechanism. Methods: The experimental research method was applied. New yeast expression vector pGAPZαA and yeast X33 were used to express recombinant ITF. The protein was purified by metal chelation affinity chromatography and anion and cation exchange chromatography. The rhITF was identified by non-reductive sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western-blotting. The rhITF was mixed with pepsin solution and trypsin solution in a volume ratio of 1∶1, respectively. After mixed with pepsin solution for 0.5, 1.0, 1.5, 2.0 h and trypsin solution for 1.0, 2.0, 4.0 h, the stability of rhITF was analyzed with non-reductive SDS-PAGE. One hundred and five male BALB/c mice aged 6-8 weeks were divided into sham injury group (n=30), burn alone group (n=45), and burn+rhITF group (n=30) according to the random number table. Mice in burn alone group and burn+rhITF group were inflicted with 30% total body surface area full-thickness burn on the back, while mice in sham injury group were simulated with burn. After burn, mice in burn+rhITF group were intragastrically administered with rhITF of 1 mg/kg, while mice in the other two groups were given the same amount of normal saline. At post injury hour 24, 15 mice in burn alone group were collected to prepare burn serum, which was used in the cell experiment. On post injury day (PID) 3, 5, and 7, 10 mice in each group were sacrificed to collect the small intestinal tissue. The pathological changes of the intestinal mucosa were observed by hematoxylin-eosin staining, and the activities of diamine oxidase (DAO) and lactic dehydrogenase (LDH) in the intestinal tissue were determined by spectrophotometry and enzyme linked immunosorbent assay. Three batches of human colorectal adenocarcinoma HT-29 cells were taken and divided into negative control group, 25 µg/mL rhITF group, 50 µg/mL rhITF group (n=3), normal control group, burn serum group, burn serum+rhITF group (n=3), and CK869 inhibitor group, CK666 inhibitor group, solvent control group (n=2), respectively, which were dealt with the corresponding treatment. After 12 h of culture, the migration of cells were observed by Transwell experiment. Another 2 batches of HT-29 cells were taken and each batch of cells were divided into normal control group, burn serum group, and burn serum+rhITF group (n=6). After 24 h of culture, the protein expressions of adenosine monophosphate activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), Ras related C3 botulinum toxin substrate 1 (Rac1), and actin-related protein 2/3 (Arp 2/3) complex, subunit 1B (ARPC1B) in the cells were detected by Western blotting, and the Rac1 activity of the cells was detected by activated magnetic bead pull-down test. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Student-Newman-Keuls test. Results: Totally 82.35 mg rhITF was gathered from per litre of fermentation broth with protein purity up to 98%, and the rhITF had good antigenicity. The rhITF was stable in pepsin solution and trypsin solution, with 45% rhITF remained after 2.0 h in trypsin solution, and there was 90% rhITF remained after 4.0 h in pepsin solution. At each time point post injury, no hyperemia, or edema was observed in intestinal mucosa of mice in sham injury group, the main pathological manifestations of intestinal mucosa in mice of burn alone group were hyperemia, edema, erosion, and hemorrhage, and the main manifestations of intestinal mucosa of mice in burn+rhITF group were hyperemia and edema on PID 3 and 5, which were alleviated on PID 7. Compared with those of burn alone group, the activities of DAO and LDH in intestinal tissue of mice in sham injury group and burn+rhITF group were significantly increased on PID 3, 5, and 7 (P<0.05 or P<0.01 ). After 12 h of culture, the number of cell migration in 25 µg/mL rhITF group was 58±12, which was obviously more than 16±5 in negative control group (P<0.01) and obviously less than 123±9 in 50 µg/mL rhITF group (P<0.05). After 12 h of culture, the number of cell migration in burn serum group was 60±13, which was significantly less than 143±11 in normal control group and 138±8 in burn serum+rhITF group (P<0.05). After 12 h of culture, the number of cell migration in solvent control group was 155±9, which was significantly more than 33±5 in CK666 inhibitor group and 28±5 in CK869 inhibitor group (P<0.01). After 24 h of culture, the protein expressions of AMPK and Rac1 of cells in burn serum group were close to those of normal control group and burn serum+rhITF group (P˃0.05), the protein expression of p-AMPK of cells in burn serum group was significantly higher than that of normal control group and burn serum+rhITF group, respectively (P<0.05 or P<0.01), and the protein expression of ARPC1B of cells in burn serum group was significantly lower than that of normal control group and burn serum+rhITF group (P<0.05). After 24 h of culture, the Rac1 activity of cells in burn serum group was significantly lower than that in normal control group and burn serum+rhITF group, respectively (P<0.05 or P<0.01). Conclusions: The rhITF obtained in this study has high purity and super stability, which can resist extreme pH and hydrolysis of protease and can relieve intestinal mucosal damage in burned mice. The rhITF can promote the migration of intestinal epithelial cells and accelerate the repair of intestinal mucosa through inhibiting phosphorylation of AMPK to maintain Rac1-Arp2/3 activity.


Assuntos
Queimaduras , Animais , Humanos , Mucosa Intestinal , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Fator Trefoil-3
13.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(2): 207-211, 2021 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-34645181

RESUMO

Objective: To analyze the antimicrobial resistance characteristics of 538 Neisseria meningitidis isolated from 2005 to 2019 in China. Method: Total of 538 Neisseria meningitidis strains collected from 30 provinces in China from 2005 to 2019. Antimicrobial susceptibility test were performed based on the standards of clinical and laboratory standardization association (CLSI) including 11 recommended antibiotics. Gradient diffusion method was used to detect the antibiotic sensitivity of Neisseria meningitidis. Results: All 538 strains were sensitive to azithromycin, meropenem, chloramphenicol, rifampicin and ceftriaxone. As to other six antibiotics, the antibiotics sensitivity rates were cefotaxime (97.4%, 524 strains), ampicillin (87.7%, 472 strains), penicillin (84.8%, 456 strains), minocycline (95.2%, 512 strains), ciprofloxacin (24.9%, 134 strains) and trimethoprim/sulfamethoxazole (11.2%, 60 strains) respectively. Conclusions: Neisseria meningitidis isolated from 2005-2019 in China were all sensitive to azithromycin, meropenem, chloramphenicol, rifampicin and ceftriaxone. It should highlight Neisseria meningitidis resistant to cefotaxime, ampicillin and penicillin. Ciprofloxacin and sulfamethoxazole are not recommended as the priority choice for clinical treatment and prophylactic medication.


Assuntos
Anti-Infecciosos , Neisseria meningitidis , Antibacterianos/farmacologia , Ceftriaxona , Humanos , Testes de Sensibilidade Microbiana
15.
Acta Biochim Biophys Sin (Shanghai) ; 53(11): 1484-1494, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34605863

RESUMO

Long non-coding RNA (lncRNA) FOXD3-AS1 expression is upregulated in lung cancer; however, its effect and mechanism on 5-fluorouracil (5-FU) resistance remain unclear. In this study, we determined the effects of FOXD3-AS1-enriched exosomes derived from lung cancer cells on the proliferation, invasion, and 5-FU resistance of lung cancer cells. Online bioinformatics database analysis showed that FOXD3-AS1 was upregulated in lung cancer progression. Real-time quantitative PCR results confirmed that FOXD3-AS1 expression was upregulated in lung cancer tissues and cell lines, and FOXD3-AS1 was greatly enriched in lung cancer cell-derived exosomes. ELAV-like RNA-binding protein 1 (ELAVL1) was identified as an RNA-binding protein of FOXD3-AS1. The lung cancer cell-derived exosomes promoted A549 cell proliferation and invasion and inhibited apoptosis caused by 5-FU, and transfection of si-FOXD3-AS1 or si-ELAVL1 in exosome-incubated A549 cells reversed these effects. Moreover, exosome-incubated A549 cells were co-transfected with si-FOXD3-AS1 and pcDNA-ELAVL1, showing the same cell proliferation, invasion, and 5-FU resistance as those of A549 cells treated with lung cancer cell-derived exosomes alone. Mechanistic studies identified that lung cancer cell-derived exosomes activated the PI3K/Akt pathway, and transfection of si-FOXD3-AS1 or treatment with the PI3K inhibitor LY294002 reversed the activation of the PI3K/Akt axis induced by exosomes. In conclusion, our study revealed that lung cancer cell-derived exosomal FOXD3-AS1 upregulated ELAVL1 expression and activated the PI3K/Akt pathway to promote lung cancer progression. Our findings provide a new strategy for lung cancer treatment.

16.
Int J Radiat Oncol Biol Phys ; 111(3S): e244, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701001

RESUMO

PURPOSE/OBJECTIVE(S): Recent studies reported that the ultra-high dose rate (FLASH) irradiation induced less healthy tissue damages compared with conventional dose rate (CONV) irradiation, this phenomenon was referred to as the FLASH effect and the underlying mechanism remains elusive. This work aims to investigate the impact of antioxidants on the FLASH effect. MATERIALS/METHODS: BALB/c nude mice were treated with the antioxidant N-Acetylcysteine (NAC) and received whole abdominal 6 MeV X-ray FLASH (> 150 Gy/s) or CONV (0.2 Gy/s) irradiation. The prescribed doses were 16 Gy (lethal dose) and 10 Gy (non-lethal dose). EBT3 films were used to confirm the dose. Mice were sacrificed 24 h post-irradiation (pi) to study acute tissue responses or followed up to 6 weeks to look at late-stage responses and the survival probability. Whole blood count, cytokine expression, histologic analysis, and TUNEL assay of intestine were used performed. RESULTS: Mice that received FLASH irradiation had a higher survival probability 6 weeks pi, and less acute and late-stage intestine damages compared to CONV irradiation. For mice that received FLASH irradiation, there are no statistically significant differences in whole blood count, survival probability and intestine damages between NAC treated group and the non-NAC treated group. However, for mice who received CONV irradiation, mice treated with NAC had significantly lower survival probability, more white blood cells, lymphocytes, and neutrophils compared to those not treated with NAC. CONCLUSION: 6 MeV X-ray FLASH irradiation can spare healthy tissues compared to CONV irradiation. Administration of antioxidant lead to more radiation induced damages under CONV irradiation but no statistic significant impact on the tissue response to FLASH irradiation. More (ongoing) experiments should be performed to study the role of antioxidants in the FLASH effect.

17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(4): 439-441, 2021 Jan 19.
Artigo em Chinês | MEDLINE | ID: mdl-34505457

RESUMO

This case report presents the diagnosis and treatment of a case with subcutaneous sparganosis.


Assuntos
Esparganose , Humanos , Esparganose/diagnóstico , Esparganose/cirurgia
19.
Phys Chem Chem Phys ; 23(37): 21262-21271, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34543374

RESUMO

We used the united-atom scheme to build three types of crystalline structures for octacosane (C28H58) and carried out molecular dynamics simulations to investigate their phase properties. By gradually heating the three polymorphs, we managed to reproduce the sequence of experimentally reported crystalline phases and rotator phases. By studying the system density, molecule morphology, chain tilt angle and cell anisotropy, we hypothesized three mechanisms behind the observed system deformations and phase transformations during the annealing process. Furthermore, our model successfully predicted the melting temperature and heat of fusion. We also reproduced the characteristics of the rotator phases and the liquid phase, validating the transferability of the united-atom scheme among the different condensed phases of octacosane. Our methodology represents an effective and efficient means of numerical study for octacosane and may be used for other members of the n-alkane family.

20.
Zhonghua Xue Ye Xue Za Zhi ; 42(8): 646-653, 2021 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-34547870

RESUMO

Objective: To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy. Methods: The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1(+) AML and 56 patients with CBFß-MYH11(+) AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results: The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFß-MYH11(+) AML than in those with RUNX1-RUNXIT1 (+) AML (P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1(+) AML, did not affect DFS (P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1(+) AML (P<0.001) , and allo-HSCT significantly prolonged DFS in these patients (P=0.010) . Conclusions: KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1(+) AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Adulto Jovem
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