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1.
BMC Cancer ; 20(1): 1095, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176731

RESUMO

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is a rare type of head and neck cancer with poor prognosis. However, till now, there is still no model predicting the survival outcomes for HSCC patients. We aim to develop a novel nomogram predicting the long-term cancer-specific survival (CSS) for patients with HSCC and establish a prognostic classification system. METHODS: Data of 2021 eligible HSCC patients were retrieved from the Surveillance, Epidemiology and End Results database between 2010 and 2015. We randomly split the whole cases (ratio: 7:3) into the training and the validation cohort. Cox regression as well as the Least absolute shrinkage and selection operator (LASSO) COX were used to select significant predictors of CSS. Based on the beta-value of these predictors, a novel nomogram was built. The concordance index (C-index), the calibration curve and the decision curve analysis (DCA) were utilized for the model validation and evaluation using the validation cohort. RESULTS: In total, cancer-specific death occurred in 974/2021 (48.2%) patients. LASSO COX indicated that age, race, T stage, N stage, M stage, surgery, radiotherapy and chemotherapy are significant prognosticators of CSS. A prognostic model based on these factors was constructed and visually presented as nomogram. The C-index of the model was 0.764, indicating great predictive accuracy. Additionally, DCA and calibration curves also demonstrated that the nomogram had good clinical effect and satisfactory consistency between the predictive CSS and actual observation. Furthermore, we developed a prognostic classification system that divides HSCC patients into three groups with different prognosis. The median CSS for HSCC patients in the favorable, intermediate and poor prognosis group was not reached, 39.0-Mo and 10.0-Mo, respectively (p < 0.001). CONCLUSIONS: In this study, we constructed the first nomogram as well as a relevant prognostic classification system that predicts CSS for HSCC patients. We believe these tools would be helpful for clinical practice in patients' consultation and risk group stratification.

2.
Biomed Pharmacother ; 131: 110524, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152900

RESUMO

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-ß-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33215278

RESUMO

Nickel (Ni) in small plateau lake sediments plays an important role in influencing the quality of lake ecosystems with a high degree of endemism and toxicity. This paper focuses on the spatial distribution and ecological risks of nickel in the sediments of Jianhu Lake, a small plateau lake in China, and the influence of pH and total organic carbon (TOC) on nickel concentrations. The results showed that average total nickel concentrations were 138.99 ± 57.57 mg/kg (n = 38) and 184.31 ± 92.12 mg/kg (n = 60) in surface sediments (0-10 cm top layer) and sediment cores (0-75 cm depth), respectively, and that the residual fraction was the main form of nickel. Simultaneously, through a semivariogram model, strong spatial dependence among pH, TOC, and the oxidizable fraction was revealed, whereas total nickel, exchangeable and the weak acid soluble fraction, reducible fraction, and residual fraction showed moderate spatial dependence. The vertical distribution revealed that nickel accumulated mainly in the bottom 5 cm (70-75 cm) of the sediment layer and that the pH was higher there, whereas TOC was concentrated mainly in the top 5 cm of sediment. Using geoaccumulation and a potential ecological risk index, moderate nickel pollution and moderate risk levels were found in most surface sediments, but moderate nickel pollution and high risk levels were observed in most sediment cores. In addition, pH and TOC were found to have a strong effect on the distribution and concentration of nickel and its fractions in the small plateau lake. In summary, nickel posed a certain degree of pollution and ecological risk, which deserves attention in the sediments of small plateau lakes.

4.
Arch Toxicol ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219404

RESUMO

Early detection strategies and improvements in cancer treatment have dramatically reduced the cancer mortality rate in the United States (US). However, cardiovascular (CV) side effects of cancer therapy are frequent among the 17 million cancer survivors in the US today, and cardiovascular disease (CVD) has become the second leading cause of morbidity and mortality among cancer survivors. Circulating biomarkers are ideal for detecting and monitoring CV side effects of cancer therapy. Here, we summarize the current state of clinical studies on conventional serum and plasma CVD biomarkers to detect and prevent cardiac injury during cancer treatment. We also review how novel exploratory tools such as genetic testing, human stem cell-derived cardiomyocytes, Omics technologies, and artificial intelligence can elucidate underlying molecular and genetic mechanisms of CV injury and to improve predicting cancer therapy-related cardiotoxicity (CTRC). Current regulatory requirements for biomarker qualifications are also addressed. We present generally applicable lessons learned from published studies, particularly on how to improve reproducibility. The combination of conventional circulating biomarkers and novel exploratory tools will pave the way for precision medicine and improve the clinical practice of prediction, detection, and management of CTRC.

5.
World Neurosurg ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171322

RESUMO

BACKGROUND: Separation surgery is performed to provide a safe gap between the epidural tumor and spinal cord for postoperative stereotactic body radiotherapy (SBRT) in cases of spinal metastases. However, there is a gap in evidence regarding sufficient tumor resection in separation surgery. We aimed to describe the prognoses according to the extent of resection in separation surgery. METHODS: This retrospective study included 36 consecutive patients who underwent separation surgery and postoperative SBRT between December 2016 and December 2019 at a single center. Local control (LC), overall survival (OS), distance of separation (DS), and quality of life parameters were analyzed. P-values <0.05 were considered statistically significant. RESULTS: Patients were assigned to the aggressive resection (ARG, n=18) or moderate resection (MRG, n=18) groups, with estimated LC and OS at 1 year of 79.0% and 75.9%, respectively. There were no significant differences between ARG and MRG in estimated LC (85.9% vs. 72.2%, P=0.317) or OS (69.3% vs. 80.9%, P=0.953) at 1 year. All 5 patients in MRG who developed local progression had less satisfactory tumor resection with DS <3 mm. A borderline significant difference in estimated LC at 1 year was noted between individuals with DS <3 mm and those with DS ≥3 mm (51.9% vs. 100.0%, P=0.053) in MRG. There was no statistical difference between ARG and MRG in quality of life parameters. CONCLUSIONS: Moderate resection of ventral dural mass didn't significantly reduce patients' prognosis in separation surgery. However, the minimal distance between the postoperative residual epidural tumor and spinal cord should be ≥3 mm.

6.
J Ethnopharmacol ; : 113583, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33189845

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG,fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

7.
Mol Plant Pathol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230892

RESUMO

Verticillium wilt is a plant vascular disease caused by the soilborne fungus Verticillium dahliae that severely limits cotton production. In a previous study, we screened Bacillus cereus YUPP-10, an efficient antagonistic bacterium, to uncover mechanisms for controlling verticillium wilt. Here, we report a novel antimicrobial cyclodextrin glycosyltransferase (CGTase) from YUPP-10. Compared to other CGTases, six different conserved domains were identified, and six mutants were constructed by gene splicing with overlap extension PCR. Functional analysis showed that domain D was important for hydrolysis activity and domains A1 and C were important for inducing disease resistance. Direct effects of recombinant CGTase on V. dahliae included reduced mycelial growth, spore germination, spore production, and microsclerotia germination. In addition, CGTase also elicited cotton's innate defence reactions. Transgenic Arabidopsis thaliana lines that overexpress CGTase showed higher resistance to verticillium wilt. Transgenic CGTase A. thaliana plants grew faster and resisted disease better. CGTase overexpression enabled a burst of reactive oxygen species production and activated pathogenesis-related gene expression, indicating that the transgenic cotton was better prepared to protect itself from infection. Our work revealed that CGTase could inhibit the growth of V. dahliae, activate innate immunity, and play a major role in the biocontrol of fungal pathogens.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33170636

RESUMO

Despite the widely explored biomaterial scaffolds in vascular tissue engineering applications lately, no ideal platform has been provided for small diameter synthetic vascular grafts mainly due to the thrombosis issue. Endothelium is the only known completely non-thrombogenic material; so, functional endothelialization onto vascular biomaterials is critical in maintaining the patency of vascular networks. Bacterial cellulose (BC) is a natural biomaterial with superior biocompatibility and appropriate hydrophilicity as potential vascular grafts. In previous studies, surface modification of active peptides such as Arg-Gly-Asp (RGD) sequences onto biomaterials has been proven to achieve accelerated and selective endothelial cell (EC) adhesion. In our study, we demonstrated a new strategy to remotely regulate the adhesion of endothelial cells based on an oscillating magnetic field and achieve successful endothelialization on the modified BC membranes. In details, we synthesized bacterial cellulose (BC), magnetic BC (MBC), and RGD peptide-grafted magnetic BC (RMBC), modified with the HOOC-PEG-COOH-coated iron oxide nanoparticles (PEG-IONs). The endothelial cells were cultured on the three materials under different frequencies of an oscillating magnetic field, including "stationary" (0 Hz), "slow" (0.1 Hz), and "fast" (2 Hz) groups. Compared to BC and MBC membranes, the cells on RMBC membranes generally show better adhesion and proliferation. Meanwhile, the "slow" frequency of a magnetic field promotes this phenomenon on RMBC and achieves endothelialization after culture for 4 days, whereas "fast" inhibits the cellular attachment. Overall, we demonstrate a non-invasive and convenient method to regulate the endothelialization process, with promising applications in vascular tissue engineering.

9.
Chemosphere ; : 128782, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33168288

RESUMO

Recently, PPCPs have attracted extensive attention as emerging pollutants. Due to the strong hydrophilicity and small molecular weight, PPCPs are difficult to be fully removed by adsorption and other processes, posing a serious threat to the ecological environment. Here, we demonstrate solvothermal synthesis of defect enrich TiO2 nanosheets through simple copper doping. Novel TiO2 nanosheets were found to be mesoporous with high specific surface area and exhibited excellent visible light response. Performance of the developed TiO2 nanosheets were evaluated towards photocatalytic degradation of two model pollutants, tetracycline and acetaminophen. Results showed robust degradation of tetracycline and acetaminophen under visible-light irradiation within 100 min. Meanwhile, the potential relationship between the structural characteristics and excellent ability of the catalyst was discussed, as well as probable mechanism. Additionally, a study on the toxicity of tetracycline solution to human skin epidermal cells showed that the toxicity of the treated solution to cells is greatly reduced. The prepared catalysts show good repeatability (a slightly decrease ca.3% after 5 cycles) and applicability, providing a reasonable design for water remediation.

10.
J Ethnopharmacol ; : 113507, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33098970

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown. AIM OF THE STUDY: This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK). MATERIALS AND METHODS: 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3-O-EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3-O-EZ and ingenol in EK and VEK were investigated. RESULTS: 3-O-EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3-O-EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%. CONCLUSION: 3-O-EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3-O-EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK.

11.
Cutan Ocul Toxicol ; : 1-7, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33103493

RESUMO

OBJECTIVE: To investigate the effect of topical sinomenine (SIN) on ocular surface damage in experimental dry eye in mice. MATERIAL AND METHODS: Experimental dry eye was created using scopolamine hydrobromide in female C57BL/6 mice. Eye drops consisting of 0.05%, or 0.1% SIN or phosphate-buffered saline (PBS) were applied to the experimental dry eye in mice. Tear product and corneal staining scores were measured at 7 and 14 days after treatment. Interleukin (IL)-1ß and tumour necrosis factor (TNF)-α levels in the SIN groups at 14 days after treatment were compared with those of other groups. RESULTS: Mice treated with 0.05% or 0.1% SIN showed a significant improvement in tear product and corneal irregularity compared to the control and PBS-treated groups. A significant decrease in the levels of IL-1ßand TNF-α was observed in the 0.05% and 0.01% SIN-treated groups. CONCLUSIONS: Topical SIN eye drop application can effectively improve clinical signs and decrease inflammation in the ocular surface, and alleviate ocular surface damage in dry eye.

12.
Curr Med Sci ; 40(5): 810-816, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123895

RESUMO

FMS-like tyrosine kinase 3 (FLT3) mutation is strongly associated with poor prognosis in acute myeloid leukemia (AML). Though many FLT3 inhibitors have been developed for clinical application with 34%-56% complete remission rate, patients would develop resistance sooner or later after initial response to tyrosine kinase inhibitors (TKIs), such as gilteritinib. And increasing studies have shown that several resistance related mutations of FLT3 emerged during the AML progression. Thus, further investigation is warranted for these FLT3mut AML patients to achieve a better treatment outcome. 4-Hydroxyphenyl retinamide (4-HPR) has been investigated extensively in animal models and clinical trials as an anticancer/chemopreventive agent and is currently used for protection against cancer development/recurrence, with minimal side effects. In this study, we performed gene-set enrichment analysis and found that down-regulated genes induced by 4-HPR were associated with FLT3-ITD gene sets. CD34+ AML stem/progenitor cells separated from 32 AML samples were treated with 4-HPR. Correlation analysis showed that AML cells with FLT3-ITD genetic alteration were more sensitive to 4-HPR treatment than those without FLT3-ITD. Next, we treated 22 primary AML cells with 4-HPR and found that 4-HPR was more toxic to AML cells with FLT3-ITD. These results indicated that 4-HPR was preferentially cytotoxic to all FLT3-ITD AML+ cells irrespective of stem/progenitor cells or blast cells. 4-HPR-induced reactive oxygen species (ROS) production and NF-κB inhibition might be the reason of 4-HPR selectivity on FLT3 mutated AML cells.

13.
J Surg Res ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33109405

RESUMO

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. METHODS: The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. RESULTS: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. CONCLUSIONS: Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.

14.
Immunity ; 53(5): 952-970.e11, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33098766

RESUMO

Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation (SHM), whereas AID targeting of non-Ig loci can generate oncogenic DNA lesions. Here, we examined the contribution of G-quadruplex (G4) nucleic acid structures to AID targeting in vivo. Mice bearing a mutation in Aicda (AIDG133V) that disrupts AID-G4 binding modeled the pathology of hyper-IgM syndrome patients with an orthologous mutation, lacked CSR and SHM, and had broad defects in genome-wide AIDG133V chromatin localization. Genome-wide analyses also revealed that wild-type AID localized to MHCII genes, and AID expression correlated with decreased MHCII expression in germinal center B cells and diffuse large B cell lymphoma. Our findings indicate a crucial role for G4 binding in AID targeting and suggest that AID activity may extend beyond Ig loci to regulate the expression of genes relevant to the physiology and pathology of activated B cells.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1105-1108, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059808

RESUMO

OBJECTIVE: To study the clinical features of children with influenza and plastic bronchitis (PB). METHODS: A retrospective analysis was performed on the medical data of 63 children with influenza and PB, including clinical manifestations, laboratory examination results, imaging findings, treatment, and outcome. RESULTS: Among the 63 children, there were 52 boys (83%) and 11 girls (17%), and 42 children had influenza A and 21 had influenza B. Among these children, 38 (60%) aged 3-6 years, and 15 (24%) had underlying diseases. The main clinical manifestations were high fever (90%), cough (95%), and shortness of breath (73%). Twenty-four children (38%) were found to have atelectasis by imaging examination. Auscultation showed that 16 children (25%) had no rales in the lungs. Of all children, 41 were admitted to the intensive care unit, and 32 required mechanical ventilation. All children underwent fiberoptic bronchoscopy and alveolar lavage. Among the 63 children, 60 recovered and 3 died. CONCLUSIONS: Influenza with PB is often observed in boys and preschool children. For influenza children with shortness of breath, even if there is no atelectasis on chest X-ray or no rales are found by auscultation, the possibility of PB still needs to be considered.

16.
Nat Commun ; 11(1): 5348, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093447

RESUMO

Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often have increased N-myristoyltransferase (NMT) expression, NMTs were proposed as anti-cancer targets. To systematically investigate this, we performed robotic cancer cell line screens and discovered a marked sensitivity of hematological cancer cell lines, including B-cell lymphomas, to the potent pan-NMT inhibitor PCLX-001. PCLX-001 treatment impacts the global myristoylation of lymphoma cell proteins and inhibits early B-cell receptor (BCR) signaling events critical for survival. In addition to abrogating myristoylation of Src family kinases, PCLX-001 also promotes their degradation and, unexpectedly, that of numerous non-myristoylated BCR effectors including c-Myc, NFκB and P-ERK, leading to cancer cell death in vitro and in xenograft models. Because some treated lymphoma patients experience relapse and die, targeting B-cell lymphomas with a NMT inhibitor potentially provides an additional much needed treatment option for lymphoma.


Assuntos
Aciltransferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Linfoma de Células B/tratamento farmacológico , Ácido Mirístico/metabolismo , Aminopiridinas/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dasatinibe/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Camundongos , Camundongos SCID , Modelos Biológicos , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/metabolismo
17.
Front Immunol ; 11: 580378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123166

RESUMO

Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells. In vivo and in vitro studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.

18.
Chem Eng J ; : 127240, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33052192

RESUMO

Antibacterial agents with enzyme-like properties and bacteria-binding ability have provided an alternative method to efficiently disinfect drug-resistance microorganism. Herein, a Fe3O4@MoS2-Ag nanozyme with defect-rich rough surface was constructed by a simple hydrothermal method and in-situ photodeposition of Ag nanoparticles. The nanozyme exhibited good antibacterial performance against E. coli (~69.4%) by the generated ROS and released Ag+, while the nanozyme could further achieve an excellent synergistic disinfection (~100%) by combining with the near-infrared photothermal property of Fe3O4@MoS2-Ag. The antibacterial mechanism study showed that the antibacterial process was determined by the collaborative work of peroxidase-like activity, photothermal effect and leakage of Ag+. The defect-rich rough surface of MoS2 layers facilitated the capture of bacteria, which enhanced the accurate and rapid attack of •OH and Ag+ to the membrane of E. coli with the assistance of local hyperthermia. This method showed broad-spectrum antibacterial performance against Gram-negative bacteria, Gram-positive bacteria, drug-resistant bacteria and fungal bacteria. Meanwhile, the magnetism of Fe3O4 was used to recycle the nanozyme. This work showed great potential of engineered nanozymes for efficient disinfection treatment.

19.
Polymers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066184

RESUMO

The industrial advancement of high-performance technologies directly depends on the thermo-mechanical properties of materials. Here we give an account of a facile approach for the bulk production of a polyethylene terephthalate (PET)/polypropylene (PP)-based nanocomposite blend with Inorganic Fullerene Tungsten Sulfide (IF-WS2) nanofiller using a single extruder. Nanofiller IF-WS2 was produced by the rotary chemical vapor deposition (RCVD) method. Subsequently, IF-WS2 nanoparticles were dispersed in PET and PP in different loadings to access impact and their dispersion behavior in polymer matrices. As-prepared blend nanocomposites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic differential scanning (DSC), dynamic mechanical analysis (DMA), and X-ray diffraction (XRD). In this work, the tensile strength of the PP/PET matrix with 1% IF-WS2 increased by 31.8%, and the thermal stability of the sample PP/PET matrix with 2% increased by 18 °C. There was an extraordinary decrease in weight loss at elevated temperature for the nanocomposites in TGA analysis, which confirms the role of IF-WS2 on thermal stability versus plain nanocomposites. In addition, this method can also be used for the large-scale production of such materials used in high-temperature environments.

20.
J Orthop Surg Res ; 15(1): 457, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023637

RESUMO

BACKGROUND: Oral tranexamic acid (TXA) has been demonstrated to reduce the blood loss in primary total knee and hip arthroplasty, but the optimal regimen of oral TXA administration is still unknown. This study aimed to find the best number of administrations of oral TXA for primary total knee and hip arthroplasty. METHODS: The PubMed, Embase, and Cochrane Library databases were searched for relevant studies published before March 20, 2020. Studies clearly reporting a comparison of multiple administrations of oral TXA for total hip/knee replacement were included, and the total blood loss (TBL), intraoperative blood loss (IBL), decline in hemoglobin (DHB), deep vein thrombosis (DVT), intramuscular venous thrombosis (IVT), length of hospital stay (LOS), and transfusion rate were evaluated. The weighted mean differences and relative risks were calculated using a fixed effects or random effects model. RESULTS: Nine studies involving 1678 patients were included in this meta-analysis (TXA 1363 (one administration, 201; two administrations, 496; three administrations, 215; four administrations, 336; five administrations, 115); placebo 315); the results show that compared with placebo groups, oral TXA could significantly reduce the TBL, IBL, DHB, LOS, and transfusion rate. In addition, the incidences of IVT and DVT were similar between the TXA and placebo groups. Moreover, two administrations of oral TXA significantly reduced the TBL and DHB compared with one administration, three administrations of oral TXA were better than two administrations, and four administrations of oral TXA were better than three administrations. CONCLUSION: Our results suggested that oral TXA could significantly reduce the blood loss and the length of hospital stay but could not increase the incidence of DVT and IVT for total joint replacement patients; additionally, the effectiveness of oral TXA administration increased as the number of administrations increased.

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