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1.
Adv Mater ; : e2000014, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32390222

RESUMO

The efficiency of heterogeneous photocatalysis for converting solar to chemical energy is low on a per photon basis mainly because of the difficulty of capturing and utilizing light across the entire solar spectral wavelength range. This challenge is addressed herein with a plasmonic superstructure, fashioned as an array of nanoscale needles comprising cobalt nanocrystals assembled within a sheath of porous silica grown on a fluorine tin oxide substrate. This plasmonic superstructure can strongly absorb sunlight through different mechanisms including enhanced plasmonic excitation by the hybridization of Co nanoparticles in close proximity, as well as inter- and intra-band transitions. With nearly 100% sunlight harvesting ability, it drives the photothermal hydrogenation of carbon dioxide with a 20-fold rate increase from the silica-supported cobalt catalyst. The present work bridges the gap between strong light-absorbing plasmonic superstructures with photothermal CO2 catalysis toward the complete utilization of the solar energy.

2.
BMC Pediatr ; 20(1): 200, 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386507

RESUMO

BACKGROUND: To report the outcomes of hepatoblastoma resected in our institution. METHODS: We diagnosed 135 children with hepatoblastoma at our institution between January 2010 and December 2017. Patients who underwent liver resection were included for analysis. However, patients who abandoned treatment after diagnosis were excluded from analysis, but their clinical characteristics were provided in the supplementary material. RESULTS: Forty-two patients abandoned treatment, whereas 93 patients underwent liver resection and were included for statistical analysis. Thirty-six, 23, 3, and 31 patients had PRETEXT stages II, III, IV, and unspecified tumours, respectively. Seven patients had ruptured tumour; 9 had lung metastasis (one patient had portal vein thrombosis concurrently). Sixteen patients underwent primary liver resection; 22, 25, and 30 patients received cisplatin-based neoadjuvant chemotherapy and delayed surgery, preoperative transarterial chemoembolization (TACE) and delayed surgery, and a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery, respectively. Forty patients had both PRETEXT and POST-TEXT information available for analysis. Twelve patients were down-staged after preoperative treatment, including 2, 8, and 2 patients from stages IV to III, III to II, and II to I, respectively. Ten patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n = 8) and I (n = 2) tumours. Seven tumours were associated with positive surgical margins, and 12 patients had microvascular involvement. During a median follow-up period of 30.5 months, 84 patients survived without relapse, 9 experienced tumour recurrence, and 4 died. The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4 ± 3.4%, and 95.2 ± 2.4%, respectively; they were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5 ± 3.7% vs 46.7 ± 19.0%, adjusted p = 0.002. OS, 97.6 ± 2.4% vs 61.0 ± 18.1%, adjusted p = 0.005), and similar among patients treated with different preoperative strategies (chemotherapy only vs TACE only vs Both: EFS, 94.7 ± 5.1% vs 91.7 ± 5.6% vs 85.6 ± 6.7%, p = 0.542. OS, 94.1 ± 5.7% vs 95.7 ± 4.3% vs 96.7 ± 3.3%, p = 0.845). CONCLUSION: The OS for patients with hepatoblastoma who underwent liver resection was satisfactory. Neoadjuvant chemotherapy and TACE seemed to have a similar effect on OS. However, the abandonment of treatment by patients with hepatoblastoma was common, and may have biased our results.

3.
Cell Death Dis ; 11(5): 328, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382008

RESUMO

Ubiquitin-specific peptidase 10 (USP10) stabilizes both tumor suppressors and oncogenes in a context-dependent manner. However, the nature of USP10's role in non-small cell lung cancer (NSCLC) remains unclear. By analyzing The Cancer Genome Atlas (TCGA) database, we have shown that high levels of USP10 are associated with poor overall survival in NSCLC with mutant p53, but not with wild-type p53. Consistently, genetic depletion or pharmacological inhibition of USP10 dramatically reduces the growth of lung cancer xenografts lacking wild-type p53 and sensitizes them to cisplatin. Mechanistically, USP10 interacts with, deubiquitinates, and stabilizes oncogenic protein histone deacetylase 6 (HDAC6). Furthermore, reintroducing either USP10 or HDAC6 into a USP10-knockdown NSCLC H1299 cell line with null-p53 renders cisplatin resistance. This result suggests the existence of a "USP10-HDAC6-cisplatin resistance" axis. Clinically, we have found a positive correlation between USP10 and HDAC6 expression in a cohort of NSCLC patient samples. Moreover, we have shown that high levels of USP10 mRNA correlate with poor overall survival in a cohort of advanced NSCLC patients who received platinum-based chemotherapy. Overall, our studies suggest that USP10 could be a potential biomarker for predicting patient response to platinum, and that targeting USP10 could sensitize lung cancer patients lacking wild-type p53 to platinum-based therapy.

4.
PLoS One ; 15(5): e0232241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407421

RESUMO

Under physiologic conditions, the dentate gyrus (DG) exhibits exceptionally low levels of activity compared to other brain regions. A sparse activation pattern is observed even when the DG is engaged to process new information; for example, only ~1-3% of neurons in the DG granule cell layer (GCL) are activated after placing animals in a novel, enriched environment. Moreover, such physiologic stimulation of GCL neurons recruits young granule cells more readily than older cells. This sparse pattern of cell activation has largely been attributed to intrinsic circuit properties of the DG, such as reduced threshold for activation in younger cells, and increased inhibition onto older cells. Given these intrinsic properties, we asked whether such activation of young granule cells was unique to physiologic stimulation, or could be elicited by general pharmacological activation of the hippocampus. We found that administration of kainic acid (KA) at a low dose (5 mg/kg) to wildtype C57BL/6 mice activated a similarly sparse number of cells in the GCL as physiologic DG stimulation by exposure to a novel, enriched environment. However, unlike physiologic stimulation, 5 mg/kg KA activated primarily old granule cells as well as GABAergic interneurons. This finding indicates that intrinsic circuit properties of the DG alone may not be sufficient to support the engagement of young granule cells, and suggest that other factors such as the specificity of the pattern of inputs, may be involved.

5.
Clin Chim Acta ; 507: 117-124, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32272157

RESUMO

Leptospira interrogans, Borrelia burgdorferi, and Treponema pallidum are important pathogenic spirochetes. The incidence of human diseases caused by pathogenic spirochetes, e.g., leptospirosis, Lyme disease, and syphilis, has been recently increased, posing a threat to public health. Mechanisms of spirochete pathogenicity are not yet fully understood, and no safe and effective vaccine to prevent and control the infection by pathogenic spirochetes is currently available. In this article, we review the progress of research into the pathogenic spirochete vaccine, mainly in terms of vaccine types. The development of relevant vaccines against pathogenic spirochetes has generally proceeded via several stages, such as the whole-cell inactivated vaccine, live attenuated vaccine, and gene-engineered vaccine, and will likely enter a new stage with the application of gene editing technology. In this review, we mainly summarized the types of pathogenic spirochete vaccines and conducted a preliminary analysis on the protective effect of immunity, and proposed a further prospect for the development of pathogenic spirochete vaccines.

6.
Pain Res Manag ; 2020: 3731510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32300383

RESUMO

Objective: The aim of this study was to demonstrate the peripheral mechanisms of chrono-acupuncture by observing acupuncture at different time points affecting relative proteins to regulate the cytoskeleton of fibroblasts differently. Methods: A total of 108 male SD rats (180-220 g) that have basic pain threshold within 3-10 s were selected and randomly divided into group A (n = 72) and control group (n = 36). After the succession of modeling with CFA injection, the rats in group A were randomly divided into model group and acupuncture group, each group containing 36 rats. Then according to the different treatment time, each group was randomly classified into 6 subgroups (ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20), each subgroup containing 6 rats (n = 6). On the second day of successful modeling, the rats in the acupuncture group received acupuncture treatment at the corresponding time point, while the control group and the model group were only tied up at the corresponding time point without any treatments. Methods of operation: use 0.5-inch needles, puncture the rats' "Zusanli" on the affected limb, with Twirling manipulation for a minute after every five minutes; the treatment lasts thirty minutes in total. After 7 days of treatments, the skin and subcutaneous tissue of rats' acupoint area of "Zusanli" on the affected limb were taken and then stained by immunofluorescence double staining method to observe the expression of the fibroblast cytoskeleton F-actin and ß-tubulin under the LSCM while using western blot to observe the expression of P38MAPK/P-P38MAPK. Results: The expression of the cytoskeleton F-actin and ß-tubulin at acupoint area in the acupuncture group was significantly higher than that in the control and model group. The effect of acupuncture on the restructure of the fibroblast cytoskeleton is different at different time points, the most effective time point was at ZT12 while the least at ZT16. Acupuncture can decrease the high expression of P-P38MAPK/P38MAPK in the model group, and the effect has time differences. The expression of P-P38MAPK/P38MAPK increased more significantly at ZT16 than ZT12. Conclusion: The remodeling difference of fibroblast cytoskeleton after receiving acupuncture treatment could be one of the peripheral bases of the chrono-acupuncture.

7.
Environ Res ; 186: 109554, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32344210

RESUMO

Biodegradable chelators (BCs) are promising substitutes for conventional washing agents in the remediation of heavy metal contaminated soil with strong complexing ability and less cost. However, great challenges for the applications of BC-assisted washing still exist, such as the assessment of the factor affecting the efficiency of metal removal and the unclear of the metal removal mechanism. Batch washing was therefore explored to evaluate the potential for four BCs for removing Cd, Pb, and Zn from polluted soils. The soil spectroscopic characteristics before and after washing were also investigated. The results demonstrated that iminodisuccinic acid (ISA) and glutamate-N, N-diacetic acid (GLDA) were an appealing alternative to commonly used non-biodegradable ethylenediaminetetraacetic acid, but glucomonocarbonic acid (GCA) and polyaspartic acid (PASP) were less efficient. Optimal parameters of BCs were determined to be a concentration of 50 mmol L-1, a pH of 5.0, a contact time of 120 min, and a solid/liquid ratio of 1:5, considering metal removal efficiencies and the suitable cost. A single removal washing could be up to 52.39% of Cd, 71.79% of Pb, and 34.13% of Zn from mine soil, and 98.28% of Cd, 91.10% of Pb, and 90.91% of Zn from polluted farmland soil. After washing, the intensity of heavy metal binding to soil colloids increased while the metal mobility reduced because of weakly bound fractions removed by BCs. The BCs-induced soil washing revealed that the possible mechanisms of metal removal included the acid dissolution, ion exchange, and surface complexation. Our findings highlight the potential application of especially ISA and GLDA as efficient washing agents to remove potentially toxic elements from contaminated soils.

8.
Int J Mol Sci ; 21(8)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326350

RESUMO

Botrytis cinerea is a pathogenic fungus that causes gray mold disease in a broad range of crops. The high intraspecific variability of B. cinerea makes control of this fungus very difficult. Here, we isolated a variant B05.10M strain from wild-type B05.10. The B05.10M strain showed serious defects in mycelial growth, spore and sclerotia production, and virulence. Using whole-genome resequencing and site-directed mutagenesis, a single nucleotide mutation in the adenylate cyclase (BAC) gene that results in an amino acid residue (from serine to proline, S1407P) was shown to be the cause of various defects in the B05.10M strain. When we further investigated the effect of S1407 on BAC function, the S1407P mutation in bac showed decreased accumulation of intracellular cyclic AMP (cAMP), and the growth defect could be partially restored by exogenous cAMP, indicating that the S1407P mutation reduced the enzyme activity of BAC. Moreover, the S1407P mutation exhibited decreased spore germination rate and infection cushion formation, and increased sensitivity to cell wall stress, which closely related to fungal development and virulence. Taken together, our study indicates that the S1407 site of bac plays an important role in vegetative growth, sclerotial formation, conidiation and virulence in B. cinerea.

9.
Medicine (Baltimore) ; 99(14): e19807, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243414

RESUMO

RATIONALE: Very severe aplastic anemia (vSAA) with active infections is always fatal. Adequate infection control before hematopoietic stem cell transplantation is recommended. PATIENT CONCERNS: A 38-year-old woman with vSAA suffered from acute perforated appendicitis and invasive pulmonary fungal infection, and she failed to respond to intense antimicrobial therapies. DIAGNOSIS: She was diagnosed with refractory vSAA with stubborn acute perforated appendicitis and invasive pulmonary fungal infection. INTERVENTIONS: We successfully completed an emergent reduced intensity conditioning-matched unrelated donor (MUD)-peripheral blood stem cell transplantation (PBSCT) as a salvage therapy in the presence of active infections. The conditioning regimens consisted of reduced cyclophosphamide 30 mg/kg/day from day-5 to day-3, fludarabine 30 mg/m/day from day-5 to day-3 and porcine-antilymphocyte immunoglobulin 15 mg/kg/day from day-4 to day-2 without total body irradiation. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day+15 and day+21. Appendiceal abscess and severe pneumonia developed after neutrophil engraftment, which were successfully managed with intense antimicrobial therapy and surgical intervention. OUTCOMES: Only limited cutaneous chronic GVHD was observed 5 months after transplantation. The patient still lives in a good quality of life 2 years after transplantation. LESSONS: Active infections may be no longer a contraindication to hematopoietic stem cell transplantation for some patients with vSAA.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Doença Aguda , Adulto , Anemia Aplástica/microbiologia , Apendicite/microbiologia , Feminino , Humanos , Pneumopatias Fúngicas/microbiologia , Doadores não Relacionados
10.
Materials (Basel) ; 13(6)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245191

RESUMO

In this article, low-density polyethylene (LDPE) was used as a matrix polymer, the Micro-ZnO and Nano-ZnO particles were used as the inorganic filler. With the melt blending method, the Nano-ZnO/LDPE(Nano-ZnO particles doping into LDPE), Micro-ZnO/LDPE(Micro-ZnO particles doping into LDPE) and Micro-Nano-ZnO/LDPE (Nano-ZnO and Micro-ZnO particles doping into LDPE in the same time) composites were prepared. Then, the inorganic filler and the composites were dealt with structural characterizations and analysis by Fourier transform infrared (FTIR), Polarization microscope (PLM), and Differential scanning calorimeter (DSC). Besides, these samples were dealt with (alternating current) AC breakdown performance test. The micro-experimental results showed that the Micro-ZnO and Nano-ZnO particles doping reduced the crystal size and increased the crystallization rate. With the change of cell structure, the crystallinity of composites increased. The crystallinity order of different samples was as follows: LDPE < Micro-ZnO/LDPE < Nano-ZnO/LDPE < Micro-Nano-ZnO/LDPE. From the breakdown of the experimental result, with the same mass fraction of the different inorganic doping of particles, the breakdown strength of these composites was different. The Nano-ZnO particle doping could improve the breakdown strength of composites effectively. Among them, the breakdown strength of Nano-ZnO/LDPE and Micro-Nano-ZnO/LDPE were 11% higher and 1.3% lower than that of pure LDPE, respectively. Meanwhile, the breakdown strength of Micro-composite was the lowest but its Weibull shape coefficient was the highest. Therefore, the Micro-ZnO doping was helpful for the Nano-ZnO dispersing in the matrix, which produced the Micro-Nano-synergy effects better.

11.
Neural Plast ; 2020: 7364649, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256557

RESUMO

Purpose: Gray matter volume loss, regional cortical thinning, and local gyrification index alteration have been documented in minimal hepatic encephalopathy (MHE). Fractal dimension (FD), another morphological parameter, has been widely used to describe structural complexity alterations in neurological or psychiatric disease. Here, we conducted the first study to investigate FD alterations in MHE. Methods and Materials: We performed high-resolution structural magnetic resonance imaging on cirrhotic patients with MHE (n = 20) and healthy controls (n = 21). We evaluated their cognitive performance using the psychometric hepatic encephalopathy score (PHES). The regional FD value was calculated by Computational Anatomy Toolbox (CAT12) and compared between groups. We further estimated the association between patients' cognitive performance and FD values. Results: MHE patients presented significantly decreased FD values in the left precuneus, left supramarginal gyrus, right caudal anterior cingulate cortex, right isthmus cingulate cortex, right insula, bilateral pericalcarine cortex, and bilateral paracentral cortex compared to normal controls. In addition, the FD values in the right isthmus cingulate cortex and right insula were shown to be positively correlated with patients' cognitive performance. Conclusion: Aberrant cortical complexity is an additional characteristic of MHE, and FD analysis may provide novel insight into the neurobiological basis of cognitive dysfunction in MHE.

12.
BMC Nephrol ; 21(1): 120, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252667

RESUMO

BACKGROUND: Few chronic kidney disease (CKD) risk prediction models have been investigated in low- and middle-income areas worldwide. We developed new risk scores for predicting incident CKD in low- and middle-income rural Chinese populations. METHODS: Data from the Handan Eye Study, which was a village-based cohort study and conducted from 2006 to 2013, were utilized as part of this analysis. The present study utilized data generated from 3266 participants who were ≥ 30 years of age. Two risk models for predicting incident CKD were derived using two-thirds of the sample cohort (selected randomly) using stepwise logistic regression, and were subsequently validated using data from the final third of the sample cohort. In addition, two simple point systems for incident CKD were generated according to the procedures described in the Framingham Study. CKD was defined as reduced renal function (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2) or the presence of albuminuria (urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g). RESULTS: The Simple Risk Score included waist circumference, systolic blood pressure (SBP), diabetes, sex, and education. The Best-fit Risk Score included urinary albumin-to-creatinine ratio, SBP, C-reactive protein, triglyceride, sex, education, and diabetes. In the validation sample, the areas under the receiver operating curve of the Simple Risk Score and Best-fit Risk Score were 0.717 (95% CI, 0.689-0.744) and 0.721 (95% CI, 0.693-0.748), respectively; the discrimination difference between the score systems was not significant (P = 0.455). The Simple Risk Score had a higher Youden index, sensitivity, and negative predictive value, with an optimal cutoff value of 14. CONCLUSIONS: Our Simple Risk Score for predicting incident CKD in a low- and middle-income rural Chinese population will help identify individuals at risk for developing incident CKD.

13.
J Hematol Oncol ; 13(1): 38, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299513

RESUMO

Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], - 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http://www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].

14.
Zhen Ci Yan Jiu ; 45(4): 299-304, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333535

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on degranulation of intraperitoneal mast cells (MCs) and expression of mitogen-activated protein kinase (MAPK) signaling related proteins, tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in urticaria rats, so as to reveal its mechanisms underlying improvement of urticaria. METHODS: Thirty-two SD rats were randomly divided into control,model,EA and medication groups (n=8 in each group). The urticaria model was established by using passive cutaneous anaphylaxis (PCA) reaction method. EA (2 Hz /15 Hz, 1 mA) was applied to bilateral "Zusanli"(ST36), "Quchi "(LI11) and "Xuehai"(SP10) for 20 min,once daily for 7 consecutive days before antigen attack. Rats of the medication group were treated by gavage of Loratadine(1 mg•kg-1•d-1)for 7 days. The diameter of cutaneous Evan's blue spots was measured to evaluate the severity of PCA. Intraperitoneal fluid smears were prepared to observe the degranulation state of MCs. The contents of TNF-α and IL-6 in the intraperitoneal fluid were detected by ELISA, and the expression of extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, c-Jun N-terminal kinase (JNK), p-JNK, P38MAPK and p-P38MAPK of the acquired intraperitoneal MCs was detected by Western blot. RESULTS: The diameter of cutaneous Evan's blue spot was significantly increased in the model group than that in the control group (P<0.01), and considerably decreased in both EA and medication groups compared with the model group(P<0.01). After modeling,the percentage of degranulated MCs, contents of TNF-α and IL-6, and expression levels of ERK, p-ERK, JNK, p-JNK, P38MAPK and p-P38MAPK were remarkably increased in the mo-del group than those in the control group (P<0.01, P<0.05). After the treatment, the percentage of degranulated MCs, contents of TNF-α and IL-6, and expression levels of p-ERK, JNK, p-JNK and p-P38MAPK were obviously decreased in both EA and medication groups relevant to the model group (P<0.01, P<0.05), while no significant changes were found in the expression of ERK in both EA and medication groups, and P38MAPK in the EA group. Compared with the model and EA groups, expression levels of P38MAPK were down-regulated in the medication group (P<0.05). CONCLUSION: EA can reduce skin allergic reaction in rats with urticaria, which may be related to its effects in inhibiting the degranulation of intraperitoneal MCs, down-regulating the expression of MAPK signaling-related proteins and the level of pro-inflammatory factors TNF-α and IL-6 in intraperitoneal MCs.

15.
PLoS One ; 15(3): e0230670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231397

RESUMO

The human positive coactivator 4 (PC4) was originally identified as a multi-functional cofactor capable of mediating transcription activation by diverse gene- and tissue-specific activators. Recent studies suggest that PC4 might also function as a novel cancer biomarker and therapeutic target for different types of cancers. siRNA knockdown studies indicated that down-regulation of PC4 expression could inhibit tumorigeneicity of A549 non-small cell lung cancer tumor model in nude mice. Here we show that AG-1031, a small molecule identified by high throughput screening, can inhibit the double-stranded DNA binding activity of PC4, more effectively than its single-stranded DNA binding activity. AG-1031 also specifically inhibited PC4-dependent transcriptional activation in vitro using purified transcription factors. AG-1031 inhibited proliferation of several cultured cell lines derived from non-small cell lung cancers (NSCLC) and growth of tumors that formed from A549 cell xenografts in immuno-compromised mice. Moreover, pre-injection of AG-1031 in these mice not only reduced tumor size, but also prevented tumor formation in 20% of the animals. AG-1031 treated A549 cells and tumors from AG-1031 treated animals showed a significant decrease in the levels of both PC4 and VEGFC, a key mediator of angiogenesis in cancer. On the other hand, all tested mice remained constant weight during animal trials. These results demonstrated that AG-1031 could be a potential therapy for PC4-positive NSCLC.

16.
J Med Syst ; 44(4): 84, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166560

RESUMO

In the original version of this article, the authors' units in the affiliation section are, unfortunately, incorrect. Jining No.1 people's hospital and Affiliated Hospital of Jining Medical University are two independent units and should not have been combined into one affiliation.

17.
Immunology ; 160(2): 209-219, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32149403

RESUMO

CD100 is an immune semaphorin constitutively expressed on T-cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T-cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8+ T-cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP-14 on mCD100 shedding for the regulation of non-cytolytic and cytolytic functions of CD8+ T-cells were also analysed in direct and indirect contact co-culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T-cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T-cells compared with the non-tumour site. Recombinant CD100 stimulation enhanced non-cytolytic and cytolytic functions of CD8+ T-cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T-cell activity. NSCLC patients had lower MMP-14 in the serum and in BALF from the tumour site. Recombinant MMP-14 mediated mCD100 shedding from CD8+ T-cell membrane, and led to promotion of CD8+ T-cell response in NSCLC patients. Overall, decreased MMP-14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung-resident CD8+ T-cell activity in NSCLC.

18.
J Exp Clin Cancer Res ; 39(1): 44, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111229

RESUMO

BACKGROUND: FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. METHODS: The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of glioma patients was examined by bioinformatic analysis. Glioblastoma (GBM) cell lines stably depleted of FKBP9 were established using lentiviruses expressing shRNAs against FKBP9. The effects of FKBP9 on GBM cells were determined by cell-based analyses, including anchorage-independent growth, spheroid formation, transwell invasion assay, confocal microscopy, immunoblot (IB) and coimmunoprecipitation assays. In vivo tumor growth was determined in both chick chorioallantoic membrane (CAM) and mouse xenograft models. RESULTS: High FKBP9 expression correlated with poor prognosis in glioma patients. Knockdown of FKBP9 markedly suppressed the malignant phenotype of GBM cells in vitro and inhibited tumor growth in vivo. Mechanistically, FKBP9 expression induced the activation of p38MAPK signaling via ASK1. Furthermore, ASK1-p38 signaling contributed to the FKBP9-mediated effects on GBM cell clonogenic growth. In addition, depletion of FKBP9 activated the IRE1α-XBP1 pathway, which played a role in the FKBP9-mediated oncogenic effects. Importantly, FKBP9 expression conferred GBM cell resistance to endoplasmic reticulum (ER) stress inducers that caused FKBP9 ubiquitination and degradation. CONCLUSIONS: Our findings suggest an oncogenic role for FKBP9 in GBM and reveal FKBP9 as a novel mediator in the IRE1α-XBP1 pathway.

19.
Adv Mater ; : e1908340, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129550

RESUMO

Perovskite single crystals (PSCs) possess superior optoelectronic properties compared to their corresponding polycrystalline films, but their applications of PSCs in high-performance, integrated devices are hindered by their heavy thickness and difficulty in scalable deposition. Here, a microchannel-confined crystallization (MCC) strategy to grow uniform and large-area PSC arrays for integrated device applications is reported. Benefiting from the confinement effect of the microchannels, solution flow dynamics is well controlled, and thus uniform deposition of PSC arrays with suitable thickness is achieved, meaning they are applicable for scale-up device applications. The resulting PSCs possess excellent optoelectronic properties in terms of a long carrier lifetime (175 ns) and an ultralow defect density (2 × 109 cm-3 ), which are comparable to the corresponding bulk crystals. The unique embedded structure of PSCs within the microchannels allows the construction of a high-integration image sensor. This work paves the way toward high-throughput growth of PSCs for integrated optoelectronic devices.

20.
Cell Death Differ ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152555

RESUMO

Sepsis is a systemic inflammatory disease causing life-threatening multi-organ dysfunction. Accumulating evidences suggest that two forms of programmed necrosis, necroptosis and pyroptosis triggered by the pathogen component lipopolysaccharide (LPS) and inflammatory cytokines, play important roles in the development of bacterial sepsis-induced shock and tissue injury. Sepsis-induced shock and tissue injury required receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) phosphorylation, caspase11 activation and gasdermin D (GSDMD) cleavage. However, the synergistic effect of necroptosis and pyroptosis in the pathological progress of sepsis remains elusive. In this study, we found that blockage of both necroptosis and pyroptosis (double deletion of Ripk3/Gsdmd or Mlkl/Gsdmd) resulted in accumulative protection against septic shock, systemic blood clotting and multi-organ injury in mice. Bone marrow transplantation confirmed that necroptosis and pyroptosis in both myeloid and nonmyeloid cells are indispensable in the progression of sepsis-induced multi-organ injury. Both RIPK3 and GSDMD signaling collaborated to amplify necroinflammation and tissue factor release in macrophages and endothelial cells, which led to tissue injury. Furthermore, cell death induced by inflammatory cytokines and high-mobility group box 1 could be prevented by double ablation of Ripk3/Gsdmd or Mlkl/Gsdmd, suggesting that a positive feedback loop interconnecting RIPK3/MLKL and GSDMD machinery and inflammation facilitated sepsis progression. Collectively, our findings demonstrated that RIPK3-mediated necroptosis and GSDMD-mediated pyroptosis collaborated to amply inflammatory signaling and enhance tissue injury in the process of sepsis, which may shed new light on two potential targets of combined therapeutic interventions for this highly lethal disorder.

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