Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 687
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Vet Res ; 16(1): 72, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127006

RESUMO

BACKGROUND: Bovine parainfluenza virus type 3 (BPIV3) is one of the important viral respiratory agents associated with the bovine respiratory disease complex (BRDC) in cattle. Previous study has demonstrated that infection of BPIV3 causes innate immune response within the host cell. ß-catenin is a key component of the Wnt/ß-catenin signal pathway which is involved in the regulation of interferon-beta (IFN-ß) transcription. Some viruses can activate while others can inhibit the Wnt/ß-catenin signaling pathway. However, the role of ß-catenin in BPIV3 infection remains unclear. RESULTS: Here we found that the expression of ß-catenin mRNA was up-regulated and ß-catenin protein was down-regulated after BPIV3 infection in MDBK cells. Moreover, it was confirmed that overexpression of ß-catenin suppressed BPIV3 replication and knockdown of ß-catenin promoted viral replication, suggesting that ß-catenin inhibits BPIV3 replication. Furthermore, IFN-ß signal pathway and virus titer analysis using the GSK3ß inhibitor (LiCl) revealed that Wnt/ß-catenin can serve as a mechanism to suppress virus replication in infected cells. The results indicated that LiCl promoted the expression and accumulation in the nucleus of ß-catenin, which further promoted the expression of IFN-ß and OSA1 and suppressed BPIV3 replication. Most importantly, BPIV3 down-regulating ß-catenin protein expression was due to degradation of GSK3ß mediated proteasome pathway. CONCLUSIONS: In summary, we discovered the relationship between ß-catenin and BPIV3 replication. These results provided further insight into the study of BPIV3 pathogenesis.

2.
Transl Oncol ; 13(3): 100736, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32092670

RESUMO

Elderly patients with esophageal carcinoma may benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen has not been determined. The aim of our study was to assess the efficiency and tolerance of treatment with a concurrent 5-fluorouracil (5-Fu)-based regimen and a taxane-based regimen combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma (ESCC). A total of 46 patients with ESCC aged older than 65 years were included in this study. The patient population was divided into two treatment groups: 24 patients who received CCRT with a 5-Fu-based regimen were allocated to the PF group, and 22 patients who received CCRT with a taxane-based regimen were allocated to the DP group. The median overall survival (OS), median progression-free survival (PFS), overall response rate, and treatment-related toxicity were assessed. For patients in the PF group, the median OS time was 27.8 ± 9.1 months, and the median PFS time was 12.5 ± 2.7 months. Patients in the DP group had comparable survival outcomes, with a median OS time of 34.4 ± 6.4 months and a median PFS time of 21.1 ± 6.4 months (P = .296 and P = .115, respectively). Grade ≥3 leukocytopenia and grade ≥2 anemia occurred in 63.6% and 59.1% of patients in the DP group, respectively, and in 25.0% and 16.7% of patients in the PF group, respectively. Our results suggest that CCRT with a taxane-based regimen results in a higher incidence of treatment-related toxicity than CCRT with a 5-Fu-based regimen but comparable survival outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32076794

RESUMO

Dendritic cell (DC) based immunotherapy is a promising approach to clinical cancer treatment. miRNAs are a class of small non-coding RNA molecules that bind to RNAs to mediate multiple events which are important in diverse biological processes. miRNA mimics and antagomirs may be potent agents to enhance DC-based immunotherapy against cancers. miRNA array analysis was used to identify a representative miR-5119 potentially regulating PD-L1 in DCs. We evaluated levels of ligands of immune cell inhibitory receptors (IRs) and miR-5119 in DCs from immunocompetent mouse breast tumor-bearing mice, and examined the molecular targets of miR-5119. We report that miRNA-5119 was downregulated in spleen DCs from mouse breast cancer-bearing mice. In silico analysis and qPCR data showed that miRNA-5119 targeted mRNAs encoding multiple negative immune regulatory molecules, including ligands of IRs such as PD-L1 and IDO2. DCs engineered to express a miR-5119 mimic downregulated PD-L1 and prevented T cell exhaustion in mice with breast cancer homografts. Moreover, miR-5119 mimic-engineered DCs effectively restored function to exhausted CD8+ T cells in vitro and in vivo, resulting in robust anti-tumor cell immune response, upregulated cytokine production, reduced T cell apoptosis, and exhaustion. Treatment of 4T1 breast tumor-bearing mice with miR-5119 mimic-engineered DC vaccine reduced T cell exhaustion and suppressed mouse breast tumor homograft growth. This study provides evidence supporting a novel therapeutic approach using miRNA-5119 mimic-engineered DC vaccines to regulate inhibitory receptors and enhance anti-tumor immune response in a mouse model of breast cancer. miRNA/DC-based immunotherapy has potential for advancement to the clinic as a new strategy for DC-based anti-breast cancer immunotherapy.

4.
Int J Mol Sci ; 21(4)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32079260

RESUMO

The use of herbicides is an effective and economic way to control weeds, but their availability for rapeseed is limited due to the shortage of herbicide-resistant cultivars in China. The single-point mutation in the acetohydroxyacid synthase (AHAS) gene can lead to AHAS-inhibiting herbicide resistance. In this study, the inheritance and molecular characterization of the tribenuron-methyl (TBM)-resistant rapeseed (Brassica napus L.) mutant, K5, are performed. Results indicated that TBM-resistance of K5 was controlled by one dominant allele at a single nuclear gene locus. The novel substitution of cytosine with thymine at position 544 in BnAHAS1 was identified in K5, leading to the alteration of proline with serine at position 182 in BnAHAS1. The TBM-resistance of K5 was approximately 100 times that of its wild-type ZS9, and K5 also showed cross-resistance to bensufuron-methyl and monosulfuron-ester sodium. The BnAHAS1544T transgenic Arabidopsis exhibited higher TBM-resistance than that of its wild-type, which confirmed that BnAHAS1544T was responsible for the herbicide resistance of K5. Simultaneously, an allele-specific marker was developed to quickly distinguish the heterozygous and homozygous mutated alleles BnAHAS1544T. In addition, a method for the fast screening of TBM-resistant plants at the cotyledon stage was developed. Our research identified and molecularly characterized one novel mutative AHAS allele in B. napus and laid a foundation for developing herbicide-resistant rapeseed cultivars.

5.
Int J Artif Organs ; 43(2): 127-136, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32000591

RESUMO

INTRODUCTION: The aim of this study was to develop a novel decellularization method in order to obtain an ideal scaffold with good biocompatibility. METHODS: The porcine corneas were treated with human serum for 5 days or serum-electrophoresis respectively. The electrophoresis (100 V/cm) was performed in sterilized buffer containing 40-mM tris base, 18-mM glacial acetic acid, and antibiotics for 1 h at 4°C. The properties of artificial corneal scaffolds were characterized by morphological and histological examinations. The biocompatibility and biological safety were examined by subcutaneous implant test and lamellar keratoplasty. RESULTS AND CONCLUSIONS: The transparency and appearance of serum-electrophoresis acellular porcine corneal matrix were better than serum acellular porcine corneal matrix. DNA and α-gal in serum-electrophoresis acellular porcine corneal matrix were more efficiently removed than those in serum acellular porcine corneal matrix (p < 0.05). The subcutaneous and corneal implantation experiments showed serum-electrophoresis acellular porcine corneal matrix had better biocompatibility compared to serum acellular porcine corneal matrix (p < 0.01). This novel serum-electrophoresis decellularization method may be valuable for preparation of xenogenic corneal tissue for clinical application.

6.
PLoS One ; 15(2): e0227766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053669

RESUMO

OBJECTIVE: In the present study, we aimed to determine whether pregravid obesity independently predicts increased risks of perinatal complications following in vitro fertilization (IVF) and the weight loss goals to reduce the risk of poor pregnancy outcomes. DESIGN: Retrospective cohort study. POPULATION: All pregnancies after first the fresh IVF cycle from January 2014 to December 2016 in the Reproductive Center affiliated to Shandong University were reviewed. A total of 3,962 eligible singleton births were stratified into cohorts based on the body mass index (BMI) definitions of the Working Group on Obesity in China (WGOC). MAIN OUTCOME MEASURES: Adverse perinatal outcomes. RESULTS: Pregravid overweight and obesity were associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and pre-eclampsia (PE), polyhydramnios, preterm premature rupture of the membranes (PPROM), placental abruption, preterm birth (PTB) <37 weeks, caesarean section (CS), fetal macrosomia, large for gestational age (LGA) >90th percentile, neonatal respiratory distress syndrome (NRDS), neonatal intensive care unit (NICU) admission and congenital anomalies as compared with the normal-weight group after adjustment of differences in age, parity, polycystic ovary syndrome (PCOS) and type of controlled ovarian hyperstimulation (COH). The increased risks of PPROM, NRDS and congenital anomalies were eliminated after adjustment of GDM development, whereas the increased risk of NRDS disappeared after adjustment of HDP. Placenta previa was not significantly different between the obese group and reference group (REF). Moreover, the rates of postpartum hemorrhage (PPH), PTB<32 weeks, small for gestational age (SGA) >90th percentile and perinatal mortality were also not significantly different between above-mentioned two groups. For obese women, a 10%-15% reduction in prepregnancy BMI was associated with significantly decreased risks of GH, CS and fetal macrosomia. For overweight women, just a 5% reduction in BMI could significantly reduce the risks of GDM, CS and fetal macrosomia. CONCLUSIONS: Pregravid obesity could independently predict a higher risk of adverse pregnancy outcomes after adjustment of differences in maternal age, parity, PCOS, and type of COH in IVF pregnancies. The potential mechanism that obesity potentiated the risks of some poor perinantal outcomes might occur through the development of GDM and HDP. A 10%-15% reduction in pregravid BMI for obese women and a 5% reduction for overweight women were associated with a significant reduction of poor perinatal complications.

7.
Biol Reprod ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31965165

RESUMO

Pelvic pain, infertility and a high postoperative recurrence rate are associated with endometriosis and adversely affect the physical and mental health of patients. Moreover, these factors place a heavy burden on families and society. The identification of endometrial stem cells (EnSCs) in the eutopic endometrium, menstrual blood and ectopic lesions of women with endometriosis not only provides new research objects in the context of endometriosis but also promotes and improves our understanding of its pathogenesis. Furthermore, based on previous studies, we reasonably suppose that dysfunctions of eutopic EnSCs play a critical role in the onset of endometriosis and directly cause abnormalities in the endometrium; subsequently, retrograde menstruation facilitates the delivery of abnormal endometrial tissues to the ovaries and pelvic cavity, where they ectopically implant, grow and form ectopic lesions. Additionally, as a chronically progressive disease, there is a delay (3-11 years) from the first onset of symptoms to the diagnosis of endometriosis. Therefore, the development of a method for early diagnosis with high sensitivity and specificity is essential for endometriosis patients and has the potential to enable early treatment, prevent endometriosis progression and relieve pain in patients. Thus, focusing on EnSCs will contribute to clarifying the potential pathogenesis of endometriosis and provide support for the application of EnSCs as therapeutic and early diagnostic targets in endometriosis treatment.

8.
Cell Prolif ; 53(2): e12754, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916359

RESUMO

The abnormalities of early post-implantation embryos can lead to early pregnancy loss and many other syndromes. However, it is hard to study embryos after implantation due to the limited accessibility. The success of embryo culture in vitro can avoid the challenges of embryonic development in vivo and provide a powerful research platform for research in developmental biology. The biophysical and chemical cues of the microenvironments impart significant spatiotemporal effects on embryonic development. Here, we summarize the main strategies which enable researchers to grow embryos outside of the body while overcoming the implantation barrier, highlight the roles of engineered microenvironments in regulating early embryonic development, and finally discuss the future challenges and new insights of early embryo culture.


Assuntos
Microambiente Celular/fisiologia , Implantação do Embrião/fisiologia , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário/fisiologia , Animais , Humanos
9.
Rapid Commun Mass Spectrom ; : e8721, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899842

RESUMO

RATIONALE: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. METHODS: After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. RESULTS: The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman, and V-type nerve agents) were shown to bind more readily to K414 on the peptide. CONCLUSIONS: This research revealed the new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from nerve agents and providing an important tool for identification of sarin or cyclosarin in terrorist attacks.

10.
Vet Microbiol ; 240: 108510, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31902512

RESUMO

Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus and causes bovine ephemeral fever of cattle and water buffalo in worldwide. Previous studies have demonstrated that infection with BEFV leads to induction of host cellular apoptosis. However, the role of apoptosis in viral replication and the interaction between viral genes and host genes involved in the process of BEFV-induced apoptosis remains unclear. Herein we investigated the interaction between viral non-structural protein α3 and cellular heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the BEFV-induced apoptosis and its role in virus replication. Overexpression of α3 gene activated caspase 3 and consequently cleaved PARP, ultimately lead to apoptosis. Moreover, virus titer of BHK-21 cells infected with BEFV and then treated respectively by the pan-caspase inhibitor (Z-VAD-FMK) and apoptosis inducer (CCCP) was determined, the results showed that apoptosis promoted viral replication. In addition, knockdown of hnRNP K gene promoted BEFV replication, whereas overexpression of hnRNP K gene had the opposite effects. More importantly, overexpression of hnRNP K inhibited virus-induced apoptosis. Subsequently, it was found that hnRNP K suppressed BEFV replication via degrading viral α3 gene and further inhibited apoptosis induced by α3 gene. Finally, the expression of hnRNP K protein was significantly down-regulated upon BEFV infection, and degradation of hnRNP K protein in BHK-21 cells infected with BEFV was mediated by viral activation of caspase 3. Taken together, these results suggest that apoptosis takes a pivotal role in BEFV replication, and interaction between viral α3 gene and host hnRNP K gene in BEFV-induced apoptosis facilitates BEFV replication.

11.
J Mol Diagn ; 22(3): 419-428, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978559

RESUMO

Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. Analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples was performed. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens.

12.
Life Sci ; 244: 117322, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958419

RESUMO

AIMS: Mitochondrial dysfunction is an early prominent feature of Alzheimer's disease (AD). In the present study, we sought to investigate whether defective mitophagy is tightly related to amyloid-ß (Aß)-induced mitochondrial dysfunction. MAIN METHODS: Immunofluorescence, western blot and transmission electron microscopy were used to examine mitophagy. Mitochondrial membrane potential was assessed using the JC-1 dye. Mitochondrial ROS was detected using MitoSOX™ Red staining. KEY FINDINGS: Aß induced mitochondrial dysfunction in HEK293 cells. Moreover, Aß induced an increase in parkin translocation to mitochondria and led to a drastic reduction in cytosolic parkin. Furthermore, Aß-treated cells displayed a microtubule-associated protein 1 light chain 3 (LC3) punctate pattern and elevated mitochondrial LC3-II levels, suggesting the upregulation of mitophagy. Notably, Aß induced the accumulation of mitochondrial p62, which was associated with impaired mitophagy. In addition, Aß-treated cells exhibited fragmented or swollen mitochondria with severely decreased cristae. We then investigated whether overexpression of parkin could protect cells against Aß-induced mitochondrial dysfunction. Interestingly, parkin overexpression inhibited Aß-induced mitochondrial dysfunction. Besides, parkin overexpression increased cytosolic and mitochondrial parkin levels as well as mitochondrial LC3-II levels in Aß-treated cells. Additionally, parkin overexpression reversed the accumulation of p62 in mitochondria, indicating that parkin overexpression restored impaired mitophagy in Aß-treated cells. Importantly, parkin overexpression remarkably reversed Aß-induced mitochondrial fragmentation. SIGNIFICANCE: Our data demonstrate that overexpression of parkin ameliorates impaired mitophagy and promotes the removal of damaged mitochondria in Aß-treated cells, indicating that upregulation of parkin-mediated mitophagy may be a potential strategy for the therapy of AD.


Assuntos
Peptídeos beta-Amiloides/efeitos adversos , Mitocôndrias/metabolismo , Doenças Mitocondriais/prevenção & controle , Ubiquitina-Proteína Ligases/metabolismo , Células HEK293 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Doenças Mitocondriais/etiologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/genética
13.
J Hazard Mater ; 385: 121561, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31740307

RESUMO

In this study, we demonstrate that a bacterial isolate Paraccocus versutus XT0.6 from the Xikuangshan antimony mine, the world largest antimony deposit, is capable of stibnite dissolution, oxidation of Sb(III), and formation of secondary Sb(V) bearing mineral. The isolate could oxidize dissolved Sb(III) aerobically and anaerobically. It was able to dissolve Sb(III) in solid minerals, which was subsequently oxidized to Sb(V) completely. Part of Sb(V) was scavenged by the formation of secondary Sb(V)-bearing mineral mopungite [NaSb(OH)6] in the biotic experiments. In contrast, Sb(III) released from mineral/rocks was only partially oxidized to Sb(V) and no secondary Sb-bearing mineral was formed in abiotic controls. These results demonstrated that microbial processes involved in the mobilization, oxidation, and transformation of antimony in minerals/rocks under ambient environmental conditions and offer new insights in biogeochemistry of Sb at mining areas.

14.
J Alzheimers Dis ; 73(1): 375-382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31796682

RESUMO

Continuous epileptic seizures hallmark status epilepticus, leading to preferential neuronal cell loss in the hippocampus that can progress into Alzheimer's disease. Previous studies have shown that status epilepticus prompts an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) to induce apoptosis of neuronal cells in the hippocampus, in a nuclear factor-kappaB (NF-κB) signaling dependent manner. Here, in an experimental rat model for status epilepticus, elicitation of sustained seizure activity was achieved by microinjection of kainic acid (KA) into the hippocampal CA3 subfield. We found that KA induced features of status epilepticus, which could be attenuated by blocking NF-κB signaling through a specific inhibitor. Interestingly, infiltration of macrophages of primarily pro-inflammatory subtype was detected in the hippocampal CA3 region immediately after KA injection. Experimental elimination of macrophages by an anti-CD115 antibody significantly attenuated the features of status epilepticus, likely through suppressing activation of NF-κB signaling. Together, these data suggest that macrophages play a critical role in NF-κB signaling-mediated status epilepticus that predisposes to Alzheimer's disease.

15.
Analyst ; 145(3): 939-945, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31825400

RESUMO

Hypochlorous acid (HOCl)/hypochlorite (OCl-), an important reactive oxygen species, plays a number of important roles in various physiological processes. However, abnormal levels of OCl- can cause many serious diseases, such as atherosclerosis, rheumatoid arthritis, cardiovascular disease, and cancer. The development of efficient methods to monitor OCl- in biological systems is therefore of particular importance. Thus, we herein report a novel isophorone-based fluorescent probe, i.e., DCOH-FR-OCl, for OCl- detection. This probe was found to exhibit colorimetric and far-red ratiometric fluorescence response signals, excellent selectivity and sensitivity for OCl- (detection limit, 88.06 nM), a remarkably large Stokes shift (158 nm), an ultrafast response (completed within 3 s), perfect photostability, and good water solubility (100% in aqueous media). DCOH-FR-OCl, as we know, is the first probe that can detect OCl- by using two different response signals at an ultrafast speed with a large Stokes shift in fully aqueous media. Furthermore, DCOH-FR-OCl can be successfully employed in the real-time imaging of endogenous and exogenous OCl- in living cells.

16.
Mol Med Rep ; 21(1): 445-453, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746428

RESUMO

Previous studies suggest that radiotherapy (RT) can induce immune activation, which not only reduces the progression of tumors, but also causes the release of tumor antigens. The combination of RT and immune checkpoint blockade, such as the inhibition of programmed cell death 1 (PD­1) and programmed cell death ligand 1 (PD­L1), has been demonstrated to yield impressive response rates. However, a substantial proportion of patients develop resistance such therapies. Previous studies have shown that indoleamine 2,3­dioxygenase (IDO) causes T cell exhaustion and increased formation of regulatory T cells (Tregs), upregulating the expression of inhibitory receptors and ligands. Therefore, the application of IDO inhibitors combined with RT may have a synergistic effect by relieving immunosuppression. Lewis lung cancer cell­bearing mice were treated with the IDO inhibitor 1­methyl­tryptophan (1MT) and/or 10 Gy RT. Tumor size was measured every day, flow cytometry was performed to measure the expression of dendritic cell (DC) maturation markers, inhibitory receptors, ligands, cytotoxic T cells and Treg phenotypic markers. Reverse transcription­quantitative PCR was used to evaluate the mRNA expression levels of IDO, PD­L1, PD­1, T cell immunoglobulin domain and mucin domain 3 (TIM­3), B­ and T­lymphocyte attenuator (BTLA) and galectin­9. Compared with the control group, treatment with 1MT or RT reduced tumor growth, however, the combination therapy was more effective than either treatment alone. Flow cytometry showed the upregulation of CD80, CD86 and the major histocompatibility complex II in spleen DCs and the concurrent downregulation of CD4, CD25 and forkhead box protein P3 in lymphocytes in the treatment groups. Compared with the control group, inhibitory receptors and ligands that affect DCs and T cells were observed, expression levels of PD­L1, PD­1, TIM­3, BTLA and galectin­9 are decreased in treatment group compared with control. IDO inhibition synergized with RT to downregulate Tregs, inhibitory receptors and ligands to prevent T cell exhaustion. By activating DCs and T cells, this combination therapy may strongly enhance antitumor immunity and inhibit tumor progression.

17.
Org Lett ; 22(1): 310-315, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31829599

RESUMO

Direct synthesis of N2-substituted triazole and triazine derivatives has been a challenge in N-heterocyclic chemistry. Under copper(II) catalysis ketene N,S-acetals, that is, alkylthio-substituted enaminones, efficiently reacted with aryldiazonium salts to allow the regioselective generation of functionally diverse N2-substituted 1,2,3-triazoles and 2,3-dihydro-1,2,4-triazines. The oxidant and base-dependent reaction yielded the five- and six-membered N-heterocyclic products, respectively. The synthetic protocol features broad substrate scopes and good functional group tolerance under mild conditions. The mechanistic studies have revealed that the reaction proceeds via alkenyl azo/imino hydrazone intermediates.

18.
Environ Sci Pollut Res Int ; 27(3): 3007-3022, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31838676

RESUMO

This study aims to evaluate the potential of fresh spent mushroom substrate (SMS) in Cd immobilization and soil improvement, compared with spent mushroom substrate biochar (SMSB) and spent mushroom substrate compost (SMSC). A simulating remediation experiment was conducted with soil at Cd concentration of 0.6, 1.2, 1.8, and 2.4 mg kg-1 and amendment addition ratio of 0.5%, 1%, 2%, and 4% for 90 days. At the end of incubation, it was found that 4%SMS addition showed the best effect both on Cd immobilization and soil improvement. It decreased Cd exchangeable fraction ratio by 52.77% (16.30% higher than 4%SMSC) and increased residual fraction ratio by 65.28% (36.34% and 49.64% higher than 4%SMSB and 4%SMSC, respectively); increased soil pH, EC, and CEC by 10.43% (3.83% higher than 4%SMSC), 11.54%, and 29.72%; and increased urease activity, sucrase activity, and catalase activity by 125.61% (43.90% and 8.54% higher than 4%SMSB and 4%SMSC, respectively), 79.46% (35.35% and 14.02% higher than 4%SMSB and 4%SMSC, respectively), and 75.68% (29.73% higher than 4%SMSB), compared with control treatment (CK) respectively. The results demonstrate that 4%SMS can be used as amendments for cadmium-contaminated soils.

19.
Ann Surg ; 271(2): 296-302, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30188400

RESUMO

OBJECTIVE: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. BACKGROUND: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. RESULTS: Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

20.
Int J Dermatol ; 59(3): 308-313, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31846069

RESUMO

BACKGROUND: The affecting factors of mucocutaneous manifestations in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients remain unclear in China. METHODS: A retrospective analysis was conducted among HIV/AIDS patients in Yunnan, China. The demographic data, mucocutaneous manifestations, CD4 cell counts, and antiretroviral therapy (ART) regimens were collected. The effects of CD4 cell count and ART on the spectrum of mucocutaneous manifestations were evaluated. RESULTS: Among 508 HIV/AIDS patients, 86.0% of cases showed mucocutaneous manifestations. The average CD4 cell count (176 cells/µl) of the patients with manifestations was significantly lower than those without manifestations (328 cells/µl) (P < 0.001). Diseases such as herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, cryptococcosis, and HIV-PPE (pruritic papular eruption) were represented quite frequently in patients with CD4 cell count <200 cells/µl (P < 0.05), but eczema was suffered by those with CD4 cell count ≥200 cells/µl (P < 0.05). ART could decline the incidence of herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, and cryptococcosis (P < 0.05). CONCLUSIONS: Mucocutaneous manifestations are closely related to the CD4 cell count and can be used as early predictors of HIV/AIDS and immune status in clinic. ART could reduce the incidence of certain mucocutaneous manifestations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA