Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 729
Filtrar
1.
Environ Toxicol Pharmacol ; : 103487, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889110

RESUMO

In the new drugs, greater than 90% of active pharmaceutical ingredients (APIs) or marketed drugs have poor solubility and bioavailability, which restrict the development of pharmaceutical preparations. The use of crystalline molecular complexes (CMCs) involving API and biocompatible precursors to improve solubility has become a shortcut for new drug development. Most of the new drugs registered in CMC form are from postmarketing drugs, and the interaction between these drugs and cytochrome P-450 (CYP) enzymes is well documented. However, it is unclear whether the interactions between CMCs of postmarketing drugs and CYP enzymes should be re-evaluated. To clarify this problem, three dipfluzine (Dip)-based CMCs, including Dip-benzoic acid (BA) cocrystal, Dip-2-hydroxybenzoate (2HB) salt and Dip-4-hydroxybenzoate (4HB) salt-cocrystal, were chosen to investigate the interaction with CYP enzymes. Metabolites of Dip-based CMCs and cocktail probe drugs were measured via LC-MS/MS in the incubation reaction system comprising recombinant CYP enzymes (rCYPs) and human liver microsomes. Dip-based CMCs not only alter Dip-mediated inhibition or activation of CYP enzymes but also change the degree to which rCYPs are involved in Dip metabolism. Specifically, the inhibitory effects of Dip and Dip-HCl were increased compared with Dip-BA and Dip-2HB for CYP1A2; Dip-BA, Dip-2HB and Dip-4HB for CYP3A4; and Dip-BA for CYP2E1. The inhibitory effects of Dip and Dip-HCl were reduced compared with Dip-2HB and Dip-4HB for CYP2C19 and Dip-4HB for CYP2E1. The effects of the alterations of Dip CMCs on the interaction between Dip and CYP enzymes are not attributed to a simple superposition of Dip and the respective precursor and may be due to the presence of interaction forces between Dip and precursor molecules. These results are the first to provide preliminary experimental evidence that CMCs change the interaction between API and CYP enzymes. Moreover, these results further suggest the importance of re-evaluating interactions with CYP enzymes when CMC strategies are used to design new drugs and even for CMCs of postmarketing drugs with known metabolic characteristics.

2.
J Am Chem Soc ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957777

RESUMO

Directed syntheses promises control over architecture and function of framework materials. In practice however, designing such syntheses requires a detailed understanding of the multistep pathways of framework formations-which remain elusive. By identifying intermediate coordination complexes, this study provides insights into the complex role of a structure-directing agent (SDA) in the synthetic realization of a promising material. Specifically, a novel molecular intermediate was observed in the formation of an indium zeolitic metal-organic framework (ZMOF) with a sodalite topology. The role of the imidazole SDA was revealed by time-resolved in situ powder X-ray diffraction (XRD) and small-angle X-ray scattering (SAXS).

3.
Pathol Res Pract ; 216(11): 153153, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32891822

RESUMO

BACKGROUND: Liver is a major metabolic organ containing many metabolic enzymes. Disorders of liver-specific enzymes can cause liver dysfunction and tumorigenesis. Previous studies indicated that 4-Hydroxyphenylpyruvate dioxygenase (HPD) plays an essential role in catalyzing the tyrosinolytic metabolism of 4-hydroxyphenylpyruvate to homogeneous acids in liver tissues. However, the clinical significance of HPD in HCC has not been obtained. Here in our study, we aimed to identify the expression and the clinical significance of HPD in hepatocellular carcinoma (HCC). METHODS: Western Blotting and qRT-PCR were employed to evaluate the level of HPD in HCC cell lines and fresh samples. The expression of HPD was further confirmed by immunohistochemistry (IHC) using a tissue microarray (TMA) cohort with a total of 778 HCC patients. Furthermore, the mRNA expression of HPD in HCC was evaluated from TCGA and GEO public databases. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between HPD expression with clinicopathological variables and survival rate of HCC patients. The cellular behaviors of transfected cells were respectively examined by CCK8 and Migration assay. RESULTS: The expression of HPD is restricted in liver compared with other cancer types. HPD mRNA and protein expression was dramatically reduced in HCC cell lines and fresh tissue samples. IHC staining in HCC TMA further showed that the decreased of HPD in paraffin-imbedded HCC samples was linked to an adverse overall postoperative survival (p < 0.001). Clinicopathologically, low expression of HPD was correlated with larger tumor size, advanced TNM staging and poor differentiaion. In addition, multivariate analyses indicated that HPD was an independent predictive factor of HCC survival. Our study pioneering validates that knockdown of HPD increases HCC cell cell growth and cell motility. CONCLUSION: Our results suggested that HPD may serve as a valuable prognostic marker, a tumor suppressor, and a potential therapeutic target for HCC patients.

4.
J Nephrol ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880885

RESUMO

BACKGROUND: The association between high-sensitivity C-reactive protein (hs-CRP) and chronic kidney disease remains controversial and long-term longitudinal studies are limited. We aim to investigate the impact of single and persistent elevation of hs-CRP on kidney outcomes. METHODS: Our study was based on a subgroup of patients with hyperglycemia from the Kailuan cohort. Patients were divided into three groups according to two consecutive hs-CRP levels: (1) no elevation (twice hs-CRP < 3 mg/L); (2) single elevation (once hs-CRP ≥ 3 mg/L); (3) persistent elevation (twice hs-CRP ≥ 3 mg/L). Kidney outcomes include kidney function decline (glomerular filtration rate [GFR] decline ≥ 30% within two years or doubling of serum c reatinine or development of end stage kidney disease [ESKD]), development and progression of proteinuria. RESULTS: Regarding the outcomes of kidney function decline, development and progression of proteinuria, we included 18,665, 11,754 and 1710 patients into analyses, respectively. After 5 years of follow-up, the number of incident cases of kidney function decline, development and progression of proteinuria were 1891, 1337 and 171, respectively. Compared to patients with no elevation of hs-CRP levels, those with persistent but not single elevation of hs-CRP were at higher risk of kidney function decline (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.23-1.64) and development of proteinuria (1.49, 1.26-1.76), but not progression of proteinuria. The results were consistent with propensity score analysis. CONCLUSION: Persistent but not single elevation of hs-CRP was independently associated with increased risk of kidney function decline, and development of proteinuria but not progression in patients with impaired fasting glucose or diabetes.

5.
Exp Cell Res ; 396(1): 112289, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32950474

RESUMO

Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed to analyze the role of Tp0136 in the migration of human microvascular endothelial (HMEC-1) cells and to explore the related mechanism. First, Tp0136 significantly promoted HMEC-1 cell migration. Furthermore, the levels of C-C motif ligand 2 (CCL2) mRNA and protein expression rose with the concentration and time increasing of Tp0136. The migration of HMEC-1 cells was significantly suppressed by an anti-CCL2 antibody and a CCR2 (the CCL2 receptor) inhibitor. Further study revealed that, in cells pretreated with anti-fibronectin antibody, anti-integrin ß1 antibody or RGD (Arg-Gly-Asp), the expression levels of CCL2 induced by Tp0136 were notably decreased. Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin ß1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin ß1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.

6.
Medicine (Baltimore) ; 99(34): e21645, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846774

RESUMO

This study assessed the association of sirtuin type 1 (SIRT1) and survivin expression with the clinicopathological features and survival of esophageal squamous cell carcinoma (ESCC) patients after concurrent chemoradiotherapy.SIRT1 and survivin proteins were immunohistochemically stained in 93 ESCC tissue specimens.SIRT1 was expressed in ESCC (80.6% vs 25.8% in normal mucosae) and survivin was expressed in 67.7% of ESCC vs 19.4% normal tissues (P < .01), and SIRT1 expression was associated with survivin expression (r = 0.39, P < .05). Furthermore, expression of both SIRT1 and survivin was associated with tumor size, depth of tumor invasion, tumor differentiation, lymph node metastasis, advanced clinical stage, and chemoradiotherapy (P < .05) as well as poor progression-free survival (PFS; P < .05) of ESCC patients after concurrent chemoradiotherapy (P < .05). Patient age, chemotherapy, tumor size, clinical stage, lymph node metastasis, and SIRT1 and survivin expression were independent PFS predictors (P < .05).Expression of both SIRT1 and survivin was associated with poor ESCC PFS.


Assuntos
Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/mortalidade , Sirtuína 1/biossíntese , Survivina/biossíntese , Adulto , Idoso , Quimiorradioterapia , Correlação de Dados , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Soft Matter ; 16(36): 8473-8481, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32820790

RESUMO

Stretchable elastomers with superhydrophobic surfaces and self-cleaning abilities are fabricated for use in wearable electronics. However, scratches or ruptures are inevitable on these elastomers, thus deteriorating their self-cleaning ability. To solve this problem, in this work, we explored the ability of a self-healing silicon elastomer to recover its self-cleaning property. A cross-linked silicon elastomer (Zn-IC-PDMS) was fabricated by incorporating imidazole-zinc coordination bonds. The superhydrophobic Zn-IC-PDMS surface was synthesized by sequentially spraying polystyrene (PS) and silica particles on it to form a micro/nano complex structure. Our study shows that the surface of the elastomer exhibited a high water-contact angle (CA) (155°), low sliding angle (SA) (∼3°), and self-cleaning ability. In addition, the surface rapidly recovered its self-cleaning ability at room temperature after ruptures had been formed across the elastomer. SEM images and photographs revealed that the recovery of the self-cleaning ability was attributed to the self-healing behavior of the Zn-IC-PDMS.

8.
World J Surg Oncol ; 18(1): 222, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32828126

RESUMO

BACKGROUND: Although RNA-binding proteins play an essential role in a variety of different tumours, there are still limited efforts made to systematically analyse the role of RNA-binding proteins (RBPs) in the survival of colorectal cancer (CRC) patients. METHODS: Analysis of CRC transcriptome data collected from the TCGA database was conducted, and RBPs were extracted from CRC. R software was applied to analyse the differentially expressed genes (DEGs) of RBPs. To identify related pathways and perform functional annotation of RBP DEGs, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the database for annotation, visualization and integrated discovery. Protein-protein interactions (PPIs) of these DEGs were analysed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Based on the Cox regression analysis of the prognostic value of RBPs (from the PPI network) with survival time, the RBPs related to survival were identified, and a prognostic model was constructed. To verify the model, the data stored in the TCGA database were designated as the training set, while the chip data obtained from the GEO database were treated as the test set. Then, both survival analysis and ROC curve verification were conducted. Finally, the risk curves and nomograms of the two groups were generated to predict the survival period. RESULTS: Among RBP DEGs, 314 genes were upregulated while 155 were downregulated, of which twelve RBPs (NOP14, MRPS23, MAK16, TDRD6, POP1, TDRD5, TDRD7, PPARGC1A, LIN28B, CELF4, LRRFIP2, MSI2) with prognostic value were obtained. CONCLUSIONS: The twelve identified genes may be promising predictors of CRC and play an essential role in the pathogenesis of CRC. However, further investigation of the underlying mechanism is needed.

9.
Addict Behav ; 112: 106573, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32805539

RESUMO

BACKGROUND: Delay Discounting (DD) relates to more frequent cannabis use, but results are variable, potentially because of variations in whether integrated or single-item measures are used, and whether the timeframe of measures is narrow or broad. Explicating the relationship between DD and cannabis use may result from comparing use indices that vary on these characteristics. METHODS: This online study of current cannabis users (n = 1,800) assessed DD and three cannabis use frequency items: number of days of use in the past month, times used per day, and weekly-monthly use. A fourth index derived with Latent Class Analysis (LCA) integrated days per month and times per day to try to better characterize frequency patterns. Effect sizes reflecting relations between cannabis use frequency indices and DD were compared. RESULTS: Three frequency classes emerged from the LCA (Low-Moderate-High). DD was significantly associated with times per day (r = 0.11, d = 0.21), days of use (r = 0.09, d = 0.18), and the LCA index (r = 0.06, d = 0.13), but not weekly-monthly use (r = 0.04, d = 0.09). Times per day was more strongly related to DD than LCA classes (p < 0.01) and weekly-monthly use (p < 0.05), but not days of use (p = 0.66). Days of use exhibited a stronger relationship with DD than weekly-monthly use (p < 0.001), but not LCA classes (p = 0.06). CONCLUSIONS: Cannabis use frequency measures with narrower timeframes may demonstrate stronger positive relationships to DD. The LCA index did not improve the relationship between frequency and DD, potentially because of shared variance between use days and times per day. Specific characteristics of cannabis use frequency may be particularly indicative of excessive DD.

10.
Theriogenology ; 157: 314-320, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32827989

RESUMO

Successful fertilization by intracytoplasmic sperm injection (ICSI) is possible as long as the sperm genome is intact, even in the context of defective sperm or sustained adverse treatment. However, there are few reports on rescuing gene-modified mouse lines after accidental death. To investigate whether sperm from a dead transgenic mouse can fertilize an oocyte and enable embryo development into a pup, Nestin-GFP transgenic male mice were sacrificed, and sperm was collected 14 h, 24 h, and 48 h after death. The collected sperm was injected into oocytes from hybrid B6D2F1 or inbred C57BL/6 N mice. The results showed that the sperm in the three groups activated oocytes from B6D2F1 and supported embryo development to the blastocyst stage. For ICSI embryos derived from B6D2F1 mice, the cleavage and blastocyst rates were significantly lower in the three experimental groups than in the control group (0 h) (P < 0.05), and the birth rate in the 24 h and 48 h groups was significantly lower than that in the 14 h and control groups (0 h). For C57BL/6N-derived ICSI embryos, the cleavage rates were significantly lower at 24 h and 48 h than at 14 h and 0 h (control group), and the birth rate in the three experimental groups was significantly lower than that in the control group (0 h). The F0 mice derived from B6D2F1 and C57BL/6 N oocytes had normal reproductive ability, and F1 mice were successfully obtained. The characteristics of the GFP gene were preserved and inherited. The histone H2AX phosphorylation assay showed that the proportion of focus-negative embryos was markedly and significantly lower in the 14 h, 24 h, and 48 h groups than in the control group (0 h). The proportion of focus-negative embryos was significantly lower at 48 h than at 14 h or 24 h. The number of foci was significantly higher in the three experimental groups than in the control group (0 h), indicating that sperm DNA sustained more damage after death and that few sperm had an intact genome. In summary, sperm obtained from mice 14 h, 24 h, and 48 h after death is capable of activating an oocyte and supporting complete embryo development into a pup. This study provides an effective way to rescue accidently died mouse strains.

11.
Phys Chem Chem Phys ; 22(34): 19100-19107, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32808610

RESUMO

By using nonequilibrium molecular dynamics, thermal transport through a series of parallel step-like graphene nanoribbon (GNR) junctions is investigated. The theoretical results show that the thermal current flows preferentially from wide GNRs to narrow ones, displaying a pronounced thermal rectification effect. Moreover, several step-like GNR-based devices are designed, and the thermally driven spin-dependent currents are calculated by using density functional theory combined with the nonequilibrium Green's function approach. We find that thermal spin-dependent currents with opposite flow directions are generated when a temperature gradient is applied along the GNRs, indicating the occurrence of a spin-dependent Seebeck effect (SDSE). More interestingly, a negative differential SDSE occurs in the thermal spin currents, and the odd and even law appears in the spin-dependent currents, thermopowers and thermoelectric conversion efficiencies. Our theoretical results indicate that the parallel step-like GNRs are potential candidates to design spin caloritronics devices hosting thermal rectification and multiple thermal-spin transport functionalities.

12.
Chem Asian J ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32776694

RESUMO

Fluoride phosphors as red components for warm white LEDs have attracted a tremendous amount of research attention. But these phosphors are extremely sensitive to moisture, which seriously limits their practical industrial applications. To tackle this problem, unlike all the straightforward preventive strategies, a reverse strategy "Good comes from bad" was successfully developed to treat the degraded K2 SiF6 : Mn4+ (D-KSFM) phosphor in the present study, which not only completely restores the luminescence properties, but also significantly enhances the moisture resistance at the same time. After treatment with an oxalic acid solution as restoration modifier, the emission intensity of the D-KSFM phosphor can be restored to 103.7% of the original K2 SiF6 : Mn4+ red phosphor (O-KSFM), and the moisture resistance is remarkably improved. The restored K2 SiF6 : Mn4+ (R-KSFM) maintains approximately 62.3% of its initial relative emission intensity after immersing in deionized water for 300 min, while the reference commercial K2 SiF6 : Mn4+ with a protective coating (C-KSFM) is only 33.2%. As a proof of general applicability, this strategy was also conducted to K2 TiF6 : Mn4+ phosphor, which is less moisture-stable than K2 SiF6 : Mn4+ . The luminescence intensity of the degraded K2 TiF6 : Mn4+ (D-KTFM) phosphor can be restored to 162.6% of original level of the K2 TiF6 : Mn4+ synthesized through a cation exchange approach without any treatment (O-KTFM). The emission intensity of the restored K2 TiF6 : Mn4+ (R-KTFM) phosphor retains 62.8% of its initial emission intensity after soaking in deionized water for 300 min. Finally, the R-KSFM phosphors were packaged into white light-emitting diodes with blue InGaN chips and Y3 Al5 O12 : Ce3+ yellow phosphors. The WLEDs display excellent color rendition with higher color rendering index, lower color temperature (WLED-II: Ra =83.6, R9 =57.3, 3743 K, ηl =199.68 lm/W; WLED-III: Ra =90.4, R9 =94.2, 2892 K, ηl =183.3 1 m/W). The above results show that the reverse strategy can be applied in those phosphor materials with poor moisture resistance to restore luminescence properties and improve moisture resistance without excessively care about the deterioration during the production, storage and transportation.

13.
PLoS Med ; 17(8): e1003180, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760065

RESUMO

BACKGROUND: Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. METHODS AND FINDINGS: We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. CONCLUSIONS: Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.


Assuntos
Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Vigilância da População , População Urbana/tendências , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Adv Sci (Weinh) ; 7(16): 2000818, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32832353

RESUMO

Growth factor deficiency in adulthood constitutes a distinct clinical syndrome with significant morbidities including abnormal body composition, reduced energy, affective disturbances, dyslipidemia, and increased cardiovascular risk. Protein replacement therapies using recombinant proteins or enzymes represent the only approved treatment. Combinatorial antibodies have shown great promise as a new class of therapeutic molecules because they act as "mechanism-based antibodies" with both agonist and antagonist activities. Using leptin, a key hormone in energy metabolism, as an example, a function-guided approach is developed to select combinatorial antibodies with high potency and full agonist activity that substitute natural growth factors in vivo. The identified antibody shows identical biochemical properties and cellular profiles as leptin, and rescues leptin-deficiency in ob/ob mice. Remarkably, the antibody activates leptin receptors that are otherwise nonfunctional because of mutations (L372A and A409E). Combinatorial antibodies have significant advantages over recombinant proteins for chronical usage in terms of immunological tolerance and biological stability.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32770259

RESUMO

The "macrotrabecular-massive" (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients.

16.
Biomed Res Int ; 2020: 2315230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733933

RESUMO

Objective: High-fat-diet- (HFD-) induced hepatic cell apoptosis is common in mice with nonalcoholic fatty liver disease (NAFLD). We aim to investigate the effect of Ginsenoside Rb1 (GRb1) on hepatocyte apoptosis. Methods: C57BL/6J mice with HFD were used to induce a liver-injured model with cell apoptosis. In addition, GRb1 was used to treat HFD-induced apoptosis in a liver with or without inhibitor of peroxisome proliferator-activated receptor γ (PPAR-γ). Results: Compared with C57BL/6J mice with common chow, there are downregulated PPAR-γ but upregulated cell apoptosis in the liver of mice with HFD. Furthermore, GRb1 elevated the hepatic PPAR-γ level and suppressed hepatocytic apoptosis. However, GW9662 abolished the effects of GRb1 on apoptosis in the liver. Conclusions: GRb1 alleviated HFD-induced apoptosis of hepatocytes of mice via PPAR-γ.

17.
J Occup Health ; 62(1): e12142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799435

RESUMO

OBJECTIVES: Occupational exposure to trichloroethylene (TCE) induces trichloroethylene hypersensitivity syndrome (TCEHS), which causes hypersensitivity dermatitis and hepatitis. However, whether TCE itself or its two metabolites, trichloroethanol (TCEOH) and trichloroacetic acid (TCA), are involved in TCEHS remains unclear. Therefore, in this study we explored the allergens causing TCEHS and characterized TCEHS-related liver injury in guinea pigs. METHOD: The guinea pig maximization test was performed using TCE, TCEOH, and TCA as candidate allergens. Skin inflammation was scored, and liver function and histopathological changes were evaluated by biochemical tests and hematoxylin and eosin staining, respectively. RESULTS: The sensitization rates for TCE, TCEOH, and TCA were 90.0%, 50.0%, and 0.0%, respectively. In the TCE and TCEOH experimental groups, the skin showed varying degrees of erythema with eosinophil granulocyte infiltration in the dermis. Additionally, serum alanine aminotransferase and γ-glutamyl transpeptidase levels increased significantly, and histological analysis revealed focal hepatocellular necrosis with inflammatory cell infiltration in the liver. CONCLUSIONS: TCE is the main cause of allergy and TCEOH is a secondary factor for allergy in guinea pigs. TCE and TCEOH can cause immune-mediated skin sensitization complicated by focal hepatic necrosis.

18.
Breast Cancer Res ; 22(1): 92, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811533

RESUMO

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis. METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression. RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival. CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.

19.
Cancer Manag Res ; 12: 6707-6717, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801903

RESUMO

Background: Long non-coding RNAs (lncRNAs) have been reported to play crucial regulatory roles in cellular activities and are associated with the carcinogenesis of various diseases. OIP5-AS1, as a novel lncRNA, function in epithelial ovarian cancer (EOC) still remains unclear. Material and Methods: qRT-PCR and Western blot analyses were performed to measure relevant expression, as needed. A series of functional experiments were performed to determine the role of OIP5-AS1 in EOC cells. Luciferase report, RNA pull down and RIP assays were performed to testify the interaction between relevant RNAs. Results: We found that OIP5-AS1 was significantly overexpressed in EOC. Knockdown of OIP5-AS1 inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process, yet facilitated apoptosis in vitro. OIP5-AS1 functioned as a competing endogenous RNA (ceRNA) to elevate ZNF217 expression through sponging miR-137. Furthermore, miR-137 inhibition and ZNF217 upregulation can reverse the effects of silencing OIP5-AS1 on the cellular activities of ovarian cancer cells. Also, depleted OIP5-AS1 hindered tumor growth and metastasis in vivo. Conclusion: OIP5-AS1 regulated ovarian cancer progression via modulating miR-137/ZNF217 signaling, suggesting that targeting OIP5-AS1 could be conducive to EOC clinical treatment.

20.
J Clin Lab Anal ; : e23510, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845540

RESUMO

OBJECTIVE: This study aimed to investigate the predictive value of microRNA-146b (miR-146b) on acute respiratory distress syndrome (ARDS) risk, and the correlation of miR-146b with disease severity and 28-day mortality in sepsis patients. METHODS: A total of 104 sepsis patients and 100 healthy controls (HCs) were consecutively enrolled, and miR-146b relative expression in their plasma samples was detected by reverse transcription-quantitative polymerase chain reaction. In sepsis patients, disease severity was assessed using Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score. ARDS occurrence and 28-day mortality were recorded. RESULTS: MiR-146b was decreased in sepsis patients compared to HCs. ARDS occurred in 30 (28.8%) sepsis patients, and miR-146b was reduced in ARDS sepsis patients compared to non-ARDS sepsis patients. Meanwhile, miR-146b distinguished ARDS sepsis patients from non-ARDS sepsis patients (area under the curve (AUC): 0.728, 95% confidence interval (CI): 0.627-0.829). Subsequent multivariate logistic regression showed that miR-146b, age, smoke, respiratory infection, and serum creatinine predicted ARDS risk independently, and their combination well-discriminated ARDS sepsis patients from non-ARDS sepsis patients (AUC: 0.863, 95% CI: 0.792-0.934). Additionally, miR-146b was negatively correlated with serum creatinine, white blood cell, C-reactive protein, APACHE II score, and SOFA score, while positively correlated with albumin. Regarding prognosis, miR-146b was decreased in 28-day sepsis deaths compared to 28-day sepsis survivors, and it discriminated 28-day sepsis deaths from 28-day sepsis survivors (AUC: 0.785, 95% CI: 0.680-0.890). CONCLUSION: MiR-146b might serve as a potential biomarker for ARDS prevention and prognostic reflection in sepsis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA