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1.
Asian J Pharm Sci ; 16(5): 653-664, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34849170

RESUMO

There is growing empirical evidence that certain types of chemotherapy and phototherapy trigger immunogenic cell death and enhance the therapeutic anticancer efficacy of genetic immunotherapy. However, the main challenge is spatiotemporally co-delivering different drugs to maximize the therapeutic index of the combination therapy. In this study, a drug delivery system (HTCP-Au/shPD-L1/DOX) was designed with a polysaccharide-wrapped shell and a condensed DNA core. To construct the HTCP-Au vector, dodecyl side chains with a polyethylenimine (PEI) head were grafted onto hyaluronic acid, and AuNPs were grafted via Au-S bonds. During drug loading, PEI arrested shRNA plasmid DNA targeting programmed cell death ligand 1 (shPD-L1) via electrostatic interactions. It also formed a PEI-DNA core that was automatically enclosed when aliphatic hydrocarbons pulled the hyaluronic acid backbone. A hydrophobic interlayer consisting of dodecyl bridge chains between the PEI-DNA core and the hyaluronic acid shell was required to accommodate hydrophobic doxorubicin. In vitro and in vivo assays demonstrated that this core-shell drug delivery system could efficiently load and transport three different drugs and effectively target tumors. Moreover, it could activate the immune system, thereby providing promising therapeutic efficacy against tumor growth and metastasis.

2.
BMC Plant Biol ; 21(1): 511, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732134

RESUMO

BACKGROUND: The walnut shell, which is composed of a large number of sclereids originating from the lignified parenchyma of the endocarp, plays an important role in fruit development and during harvesting and storage. The physical and chemical properties of walnut shells are closely related to the lignin content. Laccase is the key enzyme responsible for lignin biosynthesis by the polymerization of monolignols and plays crucial roles in secondary cell wall formation in plants. In this study, we screened and identified laccase family genes from the walnut genome and investigated the expression of laccase during endocarp lignification in walnut. RESULTS: A total of 37 laccase genes were screened from the walnut genome and distributed on nine chromosomes and classified into 6 subfamilies, among which subfamily IV showed distinct expansion. We observed that endocarp lignification started 44 days after flowering (DAF), and at later periods, the lignin content increased rapidly, with growth peaks at 44-50 DAF and 100-115 DAF. The lignification of the endocarp proceeded from the outside to the inside, as demonstrated by section staining in combination with endocarp staining. Furthermore, the changes in the expression of laccase family genes in the endocarp at different developmental stages were studied, and JrLACs showed different expression trends. The expression of nine genes showed significant increase after 44 DAF, and among these, JrLAC12-1, JrLAC12-2 and JrLAC16 showed a significant change in expression at the lignification stage. A study of the expression of JrLACs in different tissues and at various endocarp developmental stages revealed, that most JrLACs were expressed at low levels in mature tissues and at high levels in young tissues, in particular, JrLAC12-1 showed high expression in the young stems. A significant positive correlation was found between the expression of JrLAC12-1 and the variation in the lignin content in the endocarp. CONCLUSION: Laccase genes play an important role in the lignification of the walnut endocarp, and JrLACs play different roles during fruit development. This study shows that JrLAC12-1 may play a key role in the lignification of endocarp.

3.
Acta Pharm Sin B ; 11(10): 3105-3119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34729304

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3ß (GSK-3ß) interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) in alveolar macrophages (AMs), resulting in a profibrotic phenotype of AMs and promoting the development of PF. Here, we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3 (TRIB3), which interacted with GSK-3ß and stabilized GSK-3ß from ubiquitination and degradation. Elevated GSK-3ß expression phosphorylated A20 to inhibit its ubiquitin-editing activity, causing the accumulation of C/EBPß and the production of several profibrotic factors in AMs and promoting PF development. Activated C/EBPß, in turn, increased the transcription of TRIB3 and GSK-3ß, thereby establishing a positive feedback loop in AMs. The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3‒GSK-3ß interaction was an effective PF treatment. Our study reveals an intact profibrotic axis of TRIB3‒GSK-3ß‒A20‒C/EBPß in AMs, which represents a target that may provide a promising treatment strategy for PF.

4.
Lab Invest ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799662

RESUMO

Patients with chronic obstructive pulmonary disease (COPD) are characterized by an imbalance between oxidant enzymes and antioxidant enzymes. In the present study, we explored the protective effect of vitamin E on COPD and the underlying mechanisms. Targets of vitamin E were predicted by bioinformatics analysis. After establishing cigarette smoke (CS)-induced COPD rats, the expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX2), and transcriptional activity of signal transducer and activator of transcription 3 (STAT3) were measured. Additionally, the effects of vitamin E on CS-induced COPD were explored by assessing inflammation, the reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), viability of human bronchial epithelioid (HBE) cells, and the expression of EGFR/MAPK pathway-related factors after loss- and gain- function assays. Vitamin E alleviated COPD. Vitamin E inhibited MAPK signaling pathway through decreasing EGFR expression. Additionally, vitamin E suppressed CS-induced HBE cell damage. Functionally, vitamin E attenuated CS-induced inflammation, apoptosis, and ROS by inhibiting the EGFR/MAPK axis, thereby inhibiting COX2-mediated p-STAT3 nuclear translocation. Moreover, overexpression of COX2 attenuated the protective effect of vitamin E on COPD rats. The present study shows that vitamin E inhibits the expression of COX2 by negatively regulating the EGFR/MAPK pathway, thereby inhibiting the translocation of phosphorylated STAT3 to the nucleus and relieving COPD.

5.
Breast ; 60: 287-294, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34844175

RESUMO

BACKGROUND: Radiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size. METHODS: The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010-2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan-Meier, X-tile, Cox proportional hazards model and competing risk model. RESULTS: A total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors. CONCLUSION: Small tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.

6.
Value Health Reg Issues ; 29: 28-35, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801883

RESUMO

OBJECTIVES: Symptom and functional assessment is challenging in geriatric oncology care. This multicenter cross-sectional study examined the use of a multiple-symptom assessment tool, the MD Anderson Symptom Inventory (MDASI), on Chinese patients with cancer aged 65 years and older. METHODS: Patient-rated symptoms and functioning were assessed using MDASI and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire. RESULTS: The most severe symptoms were fatigue and poor appetite. The older group (75-84 years old, n = 224) reported a more severe difficulty remembering (effect size [ES] 0.32; P<.001), shortness of breath (ES 0.20; P=.020), and interference with general activity (ES 0.14; P=.027), with significantly worse physical functioning (ES -0.33; P<.001) and cognitive functioning on the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (ES 0.20; P<.001) than the younger group (65-74 years old, n = 555). For MDASI measures of the core symptoms and total interference with daily activity, Cronbach α coefficients were 0.90 and 0.93, respectively, for the younger group; and 0.93 and 0.94 for the older group, respectively. Moderate to severe (score ≥4) interference with general activity and walking on MDASI accurately indicated poor performance status (area under the curve 0.8089 and 0.7969, respectively) and lack of independence status of Activities of Daily Living (area under the curve 0.7993 and 0.8304, respectively). CONCLUSIONS: MDASI is psychometrically reliable, valid, and clinically sensitive for the measuring symptom burden and functional status of Chinese patients with cancer aged 65 years and older. MDASI could be adopted to measure multiple symptoms and physical functioning outcomes in geriatric oncology practice as well as for research on treatment benefits.

7.
Environ Technol ; : 1-11, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34779745

RESUMO

Pig farm biogas slurry is being increasingly used as a potent organic fertilizer for sustainable agriculture under circular economy. However, the effect of biogas slurry on soil pH is currently controversial, and the underlying mechanisms especially in saline-alkali soils are not well understood. A saline-alkali soil (pH = 9.2, EC = 2.0 ms/cm) was selected for soil column (0-50 cm) experiments with (BS) and without (CK) addition of pig farm biogas slurry to investigate the soil pH change and its driving factors. Our results show that the soil pH under CK ranged between 9.1 and 9.5 across different soil depths. Compared to CK, the BS-treated soil had lower pH at 0-20 cm depth and higher pH at 20-30 cm depth (P < 0.01). The soil NH4+-N concentrations were negatively correlated with pH values under BS (P < 0.01), indicating that the oxidation of ammonium mainly contributed to the decrease of soil pH. Interestingly, the anions, such as Cl-, SO42- and NO3-, were accumulated in the topsoil (0-20 cm) under BS, resulting in the changed correlations of these anions with Na+ when compared to the control. FT-IR and 13C-NMR spectra uncovered that carboxyl, amide C, and total alkyl C groups may be responsible for reducing pH of the saline-alkali soil tested. The soil surface morphology confirmed a much tighter granular aggregate microstructure when mixing the biogas slurry with the soil. Overall, we concluded that from the perspective of soil pH, the utilization of biogas slurry for improving saline-alkali soil is feasible and sustainable.

8.
Environ Toxicol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34845814

RESUMO

Overexpression or activation of Yes-associated protein (YAP) is common in cancer cells. Thus, targeting YAP may be a strategy for cancer therapy. Licochalcone A (LicA) is a primary active compound of licorice root and is known to have medicinal effects, such as antioxidant, antibacterial, antiviral, and anticancer effects. However, the anticancer pharmacological mechanism of LicA has not been investigated in cholangiocarcinoma. In this study, we investigated the antiproliferative effect of LicA and the underlying molecular mechanism in HCCC-9810 and RBE human cholangiocarcinoma cells. Our experiments indicated that LicA suppressed the growth of cholangiocarcinoma cells through inactivation of the Hippo pathway. Pescadillo ribosomal biogenesis factor 1 (PES1) was notably upregulated and related to carcinogenesis. We also found that LicA suppressed the expression and nuclear localization of PES1, which was associated with the inhibition of YAP expression and transcriptional activity.

9.
Front Cell Infect Microbiol ; 11: 654202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631595

RESUMO

The microorganisms of the reproductive tract have been implicated to affect in vitro fertilization (IVF) outcomes. However, studies on the reproductive tract microbiota of infertile women are limited and the correlation between cervical microbiota and IVF outcome remains elusive. This study aimed to characterize the cervical microbiota of IVF patients undergoing embryo transfer (ET) and assess associations between the cervical microbiota and pregnancy outcomes while exploring the underlying contributing factors. We launched a nested case-control study of 100 patients with two fresh or frozen-thawed cleavage embryos transferred per IVF cycle. Cervical swabs were collected on the day of ET and divided into four groups according to clinical pregnancy outcomes. Variable regions 3 and 4 (V3-V4) of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. In fresh IVF-ET cycles, the clinical pregnancy group (FP, n = 25) demonstrated higher α diversity (P = 0.0078) than the non-pregnancy group (FN, n = 26). Analysis of similarity (ANOSIM) revealed a significant difference in ß diversity between the two groups (R = 0.242, P = 0.001). In frozen-thawed ET cycles, though not significant, similar higher α diversity was found in the clinical pregnancy group (TP, n = 27) compared to the non-pregnancy group (TN, n = 22) and ANOSIM analysis showed a significant difference between the two groups (R = 0.062, P = 0.045). For patients in fresh IVF-ET groups, Lactobacillus, Akkermansia, Desulfovibrio, Atopobium, and Gardnerella showed differentially abundance between pregnant and non-pregnant women and they accounted for the largest share of all taxa investigated. Among them, Lactobacillus was negatively correlated with the other genera and positively correlated with serum estradiol levels. Logistic regression analysis suggested that the composition of the cervical microbiota on the day of ET was associated with the clinical pregnancy in fresh IVF-ET cycles (P = 0.030). Our results indicate that cervical microbiota composition has an impact on the outcome of assisted reproductive therapy.


Assuntos
Infertilidade Feminina , Microbiota , Estudos de Casos e Controles , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/terapia , Gravidez , Resultado da Gravidez , RNA Ribossômico 16S/genética , Estudos Retrospectivos
10.
Nat Commun ; 12(1): 6121, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675215

RESUMO

In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.

12.
Plant Physiol ; 187(3): 1713-1727, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618068

RESUMO

Sphingolipids are structural components of the lipid bilayer that acts as signaling molecules in many cellular processes, including cell death. Ceramides, key intermediates in sphingolipid metabolism, are phosphorylated by the ceramide kinase ACCELERATED CELL DEATH5 (ACD5). The loss of ACD5 function leads to ceramide accumulation and spontaneous cell death. Here, we report that the jasmonate (JA) pathway is activated in the Arabidopsis (Arabidopsis thaliana) acd5 mutant and that methyl JA treatment accelerates ceramide accumulation and cell death in acd5. Moreover, the double mutants of acd5 with jasmonate resistant1-1 and coronatine insensitive1-2 exhibited delayed cell death, suggesting that the JA pathway is involved in acd5-mediated cell death. Quantitative sphingolipid profiling of plants treated with methyl JA indicated that JAs influence sphingolipid metabolism by increasing the levels of ceramides and hydroxyceramides, but this pathway is dramatically attenuated by mutations affecting JA pathway proteins. Furthermore, we showed that JAs regulate the expression of genes encoding enzymes in ceramide metabolism. Together, our findings show that JAs accelerate cell death in acd5 mutants, possibly by modulating sphingolipid metabolism and increasing ceramide levels.

13.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3377-3384, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658225

RESUMO

Urban street canyon is one of the most important characteristics and spatial forms of cities. It is one of the most frequently used public spaces in cities, with the most serious automobile exhaust pollution and the largest population density. The unreasonable space configuration and internal composition might decrease self-purification of urban ventilation but increase local air pollutant concentration. Here, we reviewed the impacts of street canyon morphology, street trees, vehicle flow and meteorological factors on the distribution of air pollutants in street canyons. We scrutinized the relevant methods of numerical simulation, wind tunnel experiments, and field monitoring on the distribution and diffusion of air pollutants in street canyons. We recommended that future research should concentrate on the impacts of various parameters on the distribution and diffusion of air pollutants based on the field monitoring data. Meanwhile, further research should develop optimization strategies for street canyon design which is conducive to the dispersion of air pollutants, and put forward scientific support and optimization scheme for the controlling of air pollutants from the perspective of urban planning and pattern optimization.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Cidades , Conceitos Meteorológicos , Modelos Teóricos , Emissões de Veículos/análise
15.
Psychiatry Res Neuroimaging ; 317: 111387, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34509807

RESUMO

The study investigated the resting-state functional connectivity (FC) and cognitive changes in patients with depressed schizophrenia(DS) and non-depressed schizophrenia(NDS). Eighty patients with first-episode schizophrenia and 50 healthy controls (HC) were included to conduct resting-state fMRI. All participants completed MATRICS Consensus Cognitive Battery (MCCB). The right precuneus was selected as the seed in whole-brain FC analysis. Our results showed the cognitive function (All MCCB dimensions) of all schizophrenia patients were worse than HC, but no differences were found between DS and NDS. The DS had decreased FC than NDS between the right precuneus and left middle cingulate gyrus, left cerebellum, right cerebellum. The DS had increased FC than HC between the right precuneus and temporal lobe, occipital lobe, and decreased FC between the right precuneus and left cerebellum. However, the NDS had increased FC than HC between the right precuneus and left cerebellum, right cerebellum, temporal lobe, occipital lobe, left superior parietal lobule. Correlation analysis showed that FC between the right precuneus and occipital lobe was negatively correlated with visual learning in DS and with social cognition in NDS. Our results suggest DS and NDS patients have different patterns of FC, and their FC changes correlate with different domains of cognition.

16.
Life Sci ; 284: 119928, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480937

RESUMO

AIMS: Berberine is effective for type 2 diabetes mellitus (T2DM), but has limited use in clinic. This study aims to evaluate the effect of berberine combined with stachyose on glycolipid metabolism and gut microbiota and to explore the underlying mechanisms in diabetic rats. MAIN METHODS: Zucker diabetic fatty (ZDF) rats were orally administered berberine, stachyose and berberine combined with stachyose once daily for 69 days. The oral glucose tolerance and levels of blood glucose, insulin, triglyceride and total cholesterol were determined. The gut microbial profile, colonic miRNA and gene expression were assayed using Illumina sequencing. The quantitative polymerase chain reaction was used to verify the expression of differentially expressed miRNAs and genes. KEY FINDINGS: Repeated treatments with berberine alone and combined with stachyose significantly reduced the blood glucose, improved the impaired glucose tolerance, and increased the abundance of beneficial Akkermansiaceae, decreased that of pathogenic Enterobacteriaceae in ZDF rats. Furthermore, combined treatment remarkably decreased the abundances of Desulfovibrionaceae and Proteobacteria in comparison to berberine. Combined treatment evidently decreased the expression of intestinal early growth response protein 1 (Egr1) and heparin-binding EGF-like growth factor (Hbegf), and significantly increased the expression of miR-10a-5p, but berberine alone not. SIGNIFICANCE: Berberine combined with stachyose significantly improved glucose metabolism and reshaped gut microbiota in ZDF rats, especially decreased the abundance of pathogenic Desulfovibrionaceae and Proteobacteria compared to berberine alone, providing a novel strategy for treating T2DM. The underlying mechanisms may be associated with regulating the expression of intestinal Egr1, Hbegf and miR-10a-5p, but remains further elucidation.


Assuntos
Berberina/farmacologia , Colo/metabolismo , Diabetes Mellitus Experimental/genética , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Glucose/metabolismo , MicroRNAs/genética , Oligossacarídeos/farmacologia , Animais , Colo/efeitos dos fármacos , Colo/microbiologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , MicroRNAs/metabolismo , Análise de Componente Principal , Ratos Zucker , Reprodutibilidade dos Testes , Transcriptoma/genética
17.
Virulence ; 12(1): 1563-1579, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34348597

RESUMO

Ustilaginoidea virens, causing rice false smut (RFS) is an economically important ascomycetous fungal pathogen distributed in rice-growing regions worldwide. Here, we identified a novel transcription factor UvCGBP1 (Cutinase G-box binding protein) from this fungus, which is unique to ascomycetes. Deletion of UvCGBP1 affected development and virulence of U. virens. A total of 865 downstream target genes of UvCGBP1 was identified using ChIP-seq and the most significant KEGG enriched functional pathway was the MAPK signaling pathway. Approximately 36% of target genes contain the AGGGG (G-box) motif in their promoter. Among the targets, deletion of UvCGBP1 affected transcriptional and translational levels of UvPmk1 and UvSlt2, both of which were important in virulence. ChIP-qPCR, yeast one-hybrid and EMSA confirmed that UvCGBP1 can bind the promoter of UvPmk1 or UvSlt2. Overexpression of UvPmk1 in the ∆UvCGBP1-33 mutant restored partially its virulence and hyphae growth, indicating that UvCGBP1 could function via the MAPK pathway to regulate fungal virulence. Taken together, this study uncovered a novel regulatory mechanism of fungal virulence linking the MAPK pathway mediated by a G-box binding transcription factor, UvCGBP1.

18.
Immunity ; 54(9): 2042-2056.e8, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34407391

RESUMO

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.


Assuntos
Quimiocina CCL1/metabolismo , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Miofibroblastos/metabolismo , Fosfoproteínas/metabolismo , Fibrose Pulmonar/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Diferenciação Celular/fisiologia , Fibroblastos/patologia , Humanos , Camundongos , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Transdução de Sinais/fisiologia
19.
Aquat Toxicol ; 238: 105911, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34298405

RESUMO

Photodegradation is an important transformation pathway for macrolide antibiotics (MCLs) in aquatic environments, but the ecotoxicity of MCLs after phototransformation has not been reported in detail. This study investigated the effects of roxithromycin (ROX) before and after phototransformation on the growth and physio-biochemical characteristics of Chlorella pyrenoidosa, and its toxicity were explored using transcriptomics analysis. The results showed that 2 mg/L ROX before phototransformation (T0 group) inhibited algae growth with inhibition rates of 53.06%, 54.17%, 47.26%, 31.27%, and 28.38% at 3, 7, 10, 14, and 21 d, respectively, and chlorophyll synthesis was also inhibited. The upregulation of antioxidative enzyme activity levels and the malondialdehyde content indicated that ROX caused oxidative damage to C. pyrenoidosa during 21 d of exposure. After phototransformation for 48 h (T48 group), ROX exhibited no significant impact on the growth and physio-biochemical characteristics of the microalgae. Compared with the control group (without ROX and its phototransformation products), 2010 and 2988 differentially expressed genes were identified in the T0 and T48 treatment groups, respectively. ROX significantly downregulated genes related to porphyrin and chlorophyll metabolism, which resulted in the inhibition of chlorophyll synthesis and algae growth. ROX also significantly downregulated genes of DNA replication, suggesting the increased DNA proliferation risks in algae. After phototransformation, ROX upregulated most of the genes associated with the porphyrin and chlorophyll metabolism pathway, which may be the reason that the chlorophyll content in T48 treatment group showed no significant difference from the control group. Almost all light-harvesting chlorophyll a/b (LHCa/b) gene family members were upregulated in both T0 and T48 treatment groups, which may compensate part of the stress of ROX and its phototransformation products.

20.
Int J Clin Exp Pathol ; 14(6): 670-679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239668

RESUMO

AIMS: CD4 T cell count and optimal timing of antiretroviral therapy (ART) during tuberculosis (TB) treatment are challenging. We conducted a meta-analysis to assess the association of CD4 T cell count and timing of ART initiation with immune reconstitution inflammatory syndrome (IRIS) and all-cause mortality of patients co-infected with HIV/TB. METHODS: We conducted an electronic search of clinical studies dated from January 1980 to December 2019 in PubMed and EMBASE. Randomized, controlled trials evaluating low-base CD4 T cell count (< 50 cells/µL) versus high-base CD4 T cell count (≥ 50 cells/µL), and/or early ART initiation (1 to 28 days after starting TB treatment) versus delayed ART initiation (≥ 28 days after starting TB treatment) were included. The primary endpoints were all-cause mortality and TB-related immune reconstitution inflammatory syndrome (IRIS-TB). The risk ratio (RR) was calculated as a measure of intervention effect. Mantel-Haenszel method was used to estimate the RR. RESULTS: Ten trials (n = 5226) were conducted in North America, Africa, and Asia. We found that low-baseline CD4 T cell count increased the incidence of TB-associated IRIS (RR, 1.47; 95% CI, 1.24-1.75; I2 = 58%) and all-cause mortality (RR, 2.42; 95% CI, 1.71-3.42; I2 = 41%) compared with high baseline CD4 T cell count, and early ART initiation increased the incidence of TB-associated IRIS compared with delayed ART initiation (RR, 1.80; 95% CI, 1.57-2.07; I2 = 74%). However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74-1.12; I2 = 49%) compared with delayed ART initiation. CONCLUSIONS: The present study demonstrates that low-baseline CD4 T cell count (< 50 cells/µL) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS and all-cause mortality. Early ART initiation (≤ 28 days) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS. However, evidence is insufficient to refute or support a survival benefit conferred by the comparison between early ART initiation (≤ 28 days) and delayed ART initiation.

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