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1.
J Cancer ; 13(7): 2126-2137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517410

RESUMO

Most colorectal cancer (CRC) patients are insensitive to immune checkpoint inhibitors (ICIs) due to the immunosuppressive tumor microenvironment (TME). Epigenetic factors such as the bromo-and extraterminal domain (BET) family proteins may be responsible for the immunosuppressive microenvironment. Previous studies have shown that inhibitors of BET family proteins have the potential to remodel the immunosuppressive TME. However, data on the role of BET inhibitors in immune microenvironment in CRC remains unclear. Here, we evaluated the immunoregulatory role of JQ1, a BET inhibitor, in CRC. Transcriptome sequencing data showed that JQ1 decreased CD274 expression and increased H2Kb expression in MC38 cells. Flow cytometry assays demonstrated that JQ1 decreased cell-surface PD-L1 expression in MC38 and HCT116 cells. Moreover, JQ1 significantly increased cell-surface expression of major histocompatibility complex class I (MHC-I) in MC38 cells and HCT116 cells. Antigen-specific cytotoxic T lymphocytes (CTLs) assay demonstrated that JQ1 enhanced the MHC-I-mediated cytotoxicity of CTLs. Mouse colon cancer cell line MC38 was used to establish the syngeneic mouse tumor model. Compared with the control, JQ1 significantly inhibited tumor growth and prolonged the overall survival of the mice. Besides, JQ1 did not only inhibit tumor growth by enhancing anti-tumor immunity, but also promoted the anti-tumor effect of PD-1 antibody. In addition, our data showed that JQ1 reduced infiltration of intratumoral regulatory T cells (Treg), thus remodeling the immunosuppressive TME. Taken together, these results highlight a new approach that enhances anti-PD-1 sensitivity in CRC.

2.
iScience ; 25(5): 104249, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35521536

RESUMO

L3MBTL2 is a crucial component of ncPRC1.6 and has been implicated in transcriptional repression and chromatin compaction. However, the repression mechanism of L3MBTL2 and its biological functions are largely undefined. Here, we found that L3MBTL2 plays a distinct oncogenic role in tumor development. We demonstrated that L3MBTL2 repressed downstream CGA through an H2AK119ub1-dependent mechanism. Importantly, the binding of the MGA/MAX heterodimer to the E-box on the CGA promoter enhanced the specific selective repression of CGA by L3MBTL2. CGA encodes the alpha subunit of glycoprotein hormones; however, we showed that CGA plays an individual tumor suppressor role in PDAC. Moreover, CGA-transcript1 (T1) was identified as the major transcript, and the tumor suppression function of CGA-T1 depends on its own glycosylation. Furthermore, glycosylated CGA-T1 inhibited PDAC, partly by repression of autophagy through multiple pathways, including PI3K/Akt/mTOR and TP53INP2 pathways. These findings reveal the important roles of L3MBTL2 and CGA in tumor development.

3.
Transpl Immunol ; : 101611, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500846

RESUMO

BACKGROUND: Since a micro-infusion pump continuously pumps drugs at a low speed, it has the risk of complications including venous blood return, indwelling needle blockage, and the lack of regular delivery of drugs. This study aimed to investigate venous blood return and indwelling needle blockage after cardiac surgery when a micro-infusion pump was used at a very low flow rate of only 2 ml/h without any accompanying fluid. METHODS: A total of 215 patients, who were hospitalized at the Second Hospital of Shandong University between May and December 2020, received a continuous intravenous administration of drugs via a micro-infusion pump at 2 ml/h without or with accompanying fluid. These patients were randomly divided into an observation group (108 patients) and a control group (107 patients). In the observation group, drugs were administered at 2 ml/h without any additional fluid. In contrast, the control group received drugs also at 2 ml/h but with a normal saline through an intravenous drip. The venous backflow, blockage of the indwelling needle and catheter, and other adverse reactions were evaluated In addition, the volume of an accompanying fluid as well as the mean of nursing work time and additional costs were calculated. RESULTS: The main finding of this analysis showed no statistically significant differences in the number of complications such as venous backflow, blockage of the indwelling needle or catheter, or any adverse reactions between the observational and control groups (P > 0.05). Compared to the control group, the observation group had significantly reduced the amount of fluid intake (P < 0.001). In addition, the 2 ml/h infusion tempo without any additional fluid shortened nursing hours (P < 0.001), and thus reduced costs for the observation group vs. the control group. CONCLUSIONS: It is feasible and safe to administer drugs via a micro-infusion pump at the slow 2 ml/h tempo without any accompanying fluid to patients after surgery requiring minimal volume of fluids.

4.
Ying Yong Sheng Tai Xue Bao ; 33(3): 793-800, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35524533

RESUMO

Soil microorganism is an important indicator of soil health and plays a critical role in biogeochemical processes. We collected soil samples from a multi-year in-situ field experiment with two cropping modes (maize monocropping and maize-potato intercropping) subjected to four nitrogen (N) levels (N0, 0 kg·hm-2; N125, 125 kg·hm-2; N250, 250 kg·hm-2; N375, 375 kg·hm-2). By using the Biolog-ECO microplate method, soil microbial metabolic activity, diversity and utilization of six carbon groups were analyzed. The results showed that N application significantly increased the average well color development (AWCD) values, Simpson and Shannon indices, with the highest value at N250 in mono- and inter-cropped soils. Moreover, N application promoted the utilization of amino acids, amines and phenolic compounds, but decreased the utilization of polymers. Compared with monocropping at the same N level, intercropping improved the AWCD values, Simpson and Shannon indices, with a maximal improvement at N250. Intercropping and nitrogen application significantly affected the metabolic activities of the six carbon-source groups. In addition, intercropping improved the utilization of labile carbon sources, such as amino acids and carbohydrates. Results of the redundancy analysis and linear regression showed that intercropping and N application elevated AWCD values by increasing soil temperature, water content, and soil organic carbon content. Therefore, the changes in soil physicochemical properties after intercropping were the main reason for the enhancement of microbial metabolic activity under N application.


Assuntos
Nitrogênio , Solo , Agricultura/métodos , Aminoácidos/metabolismo , Carbono/metabolismo , Nitrogênio/análise , Solo/química , Microbiologia do Solo , Zea mays
5.
Environ Monit Assess ; 194(6): 409, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524889

RESUMO

Land use/land cover (LULC) changes due to urban growth on the regional scale affect land surface temperature (LST). The present study aims to assess the LULC changes and their impact on LST over Mardan and Charsadda districts of Khyber Pakhtunkhwa (KP), Pakistan, in the period from 1990 to 2019. Landsat satellite (TM& ETM +) datasets in the period from 1990 to 2010 and Sentinel-2 images from 2016 to 2019 were used in this study. All the datasets were pre-processed and the LULC types were classified by maximum likelihood classification algorithm. The vegetation degradation was computed from normalized difference vegetation index (NDVI), and the LST was derived based on the LULC changes. The results showed that the overall accuracy of LULC classification was 87.84%. Dramatic LULC changes were observed during the last three decades, where the vegetation degradation area was decreased from 1307.8 (59.27%) to 1147.6 km2 (52.1%) and the barren land area increased from 816.6 (37.07%) to 961.4 km2 (42.64%). Similarly, the built-up area has also increased from 57.2 (2.5%) to 104.3 km2 (4.73%) in the years 1990 and 2019, respectively. These variations in LULC types have significantly influenced the LST from 1990 to 2019; specifically, the LST of built-up area, barren land, and vegetation cover increased from 20.1 to 32.1 °C, 21.5 to 35.5 °C, and 17.1 to 28.2 °C, respectively. The regression line plotted defines that the LST has a negative correlation with NDVI and a positive correlation with normalized difference of built-up index (NDBI). In particular, the vegetation and land covers dramatically transformed to barren land and/or to urban development over the study area in the period from 1990 to2019, which has severely affected the LST and the natural resources of the study area. Therefore, our study will be very helpful for managing the rapid environmental changes and urban planning.


Assuntos
Monitoramento Ambiental , Reforma Urbana , Monitoramento Ambiental/métodos , Paquistão , Temperatura , Urbanização
6.
Ann Transl Med ; 10(7): 413, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530951

RESUMO

Background: The pathogenesis of Crohn's disease (CD) is unknown; however, angiogenesis is known to play an important role in the disease. The present research suggests that microRNA-21 (miR-21) may play a positive regulatory role in disordered angiogenesis in CD. Methods: C57 wild-type mice were divided into 6 groups. On day 0, all mice in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) group were given an enema at the concentration of TNBS 100 mg/kg mouse body weight (solvent 50% alcohol). In the control group, the enema was performed with 50% alcohol. On day 0, 2, 4, and 6, the mice of the agomir-21 + TNBS group and the agomir control + TNBS group were injected with 200 µL, 5 nmol agomir-21 or agomir control [dissolved in ribonuclease (RNase)-free water] by tail vein injection, while the antagomir-21 + TNBS group and the antagomir control + TNBS group were injected with 200 µL, 20 nmol antagomir-21 or antagomir control (dissolved in RNase-free water). The body weight and disease activity index (DAI) score were recorded daily. The colons were obtained to assess macro and microscopic colon damage. The inferior vena cava and the accompanying abdominal aorta were chosen to detect the protein expression of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT)/vascular endothelial growth factor (VEGF) axis through western blotting. Serum interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The distribution and expression of neovascularization were demonstrated by cluster of differentiation 31 (CD31) immunohistochemistry. Results: Compared with the only-TNBS group, the agomir-21 + TNBS group showed significantly severer colitis symptoms and more abnormal vascular hyperplasia, while the antagomir-21 + TNBS group showed symptom relief and reduced vascular hyperplasia. In addition, agomir-21 obviously inhibited the expression of PTEN and activated the PI3K/AKT/VEGF pathway in mice induced by TNBS, while antagomir-21 effectively antagonized this effect. Conclusions: miR-21 can promote the progression of colitis in mice induced by TNBS and aggravate the disordered angiogenesis by regulating the PTEN/PI3K/AKT axis. Intravenous injection of miR-21 antagonists can effectively relieve the symptoms of colitis and inhibit colonic angiogenesis.

7.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2090-2098, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531725

RESUMO

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Benchmarking , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/análise , Ácido Glicirrízico/análise , Controle de Qualidade
8.
BMC Genomics ; 23(1): 341, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501708

RESUMO

BACKGROUND: Receptor interacting serine/threonine kinase 2 (RIP2), ubiquitous in many tissue/cell types, is the key regulator of immune and inflammatory responses for many diseases, including avian pathogenic E. coli (APEC), which causes a wide variety of localized or systemic infections. However, the molecular mechanisms by which RIP2 drives its transcriptional program to affect immune and inflammatory response upon APEC infection remains poorly understood. RESULTS: In this study, RNA-seq and bioinformatics analyses were used to detect gene expression and new direct/indirect RIP2 targets in the treatments of wild type HD11 cells (WT), RIP2 knockdown cells (shRIP2), APEC stimulation cells (APEC), and RIP2 knockdown cells combined with APEC infection (shRIP2 + APEC). The results revealed that a total of 4691 and 2605 differentially expressed genes (DEGs) were screened in shRIP2 + APEC vs. APEC and shRIP2 vs. WT, respectively. Functional annotation analysis showed that apoptosis, MAPK, p53, Toll-like receptor, and Nod-like receptor signaling pathways were involved in APEC-induced RIP2 knockdown HD11 cells. By analyzing the enriched pathway and gene networks, we identified that several DEGs, including HSP90AB1, BID, and CASP9 were targeted by RIP2 upon APEC infection. CONCLUSION: As a whole, this study can not only provide data support for constructing gene networks of RIP2 knockdown with APEC challenge but also provide new ideas for improving the immune and inflammatory response.


Assuntos
Escherichia coli , Redes Reguladoras de Genes , Animais , Galinhas/metabolismo , Perfilação da Expressão Gênica , Macrófagos
9.
BMC Gastroenterol ; 22(1): 215, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505304

RESUMO

BACKGROUND: CircRNA circ-ATAD1 has been characterized as an oncogenic circRNA in gastric cancer, while its role in colorectal cancer (CRC) is unknown. This study was carried out to explore the role of circ-ATAD1 in CRC. METHODS: Paired CRC and adjacent non-tumor tissue samples collected from 64 CRC patients were subjected to RNA extractions and RT-qPCRs to analyze the expression of circ-ATAD1, premature miR-618, and mature miR-618 in CRC. The effects of circ-ATAD1 overexpression on miR-618 maturation were analyzed by transfecting circ-ATAD1 expression vector into CRC cells, followed by determining the expression of premature miR-618 and mature miR-618 using RT-qPCR. The subcellular location of circ-ATAD1 was analyzed by nuclear fractionation assay, and the interaction between circ-ATAD1 and premature miR-618 was analyzed by RNA pull-down assay. The roles of circ-ATAD1, premature miR-618, and mature miR-618 in regulating CRC cell proliferation were explored by CCK-8 assay. RESULTS: Circ-ATAD1 was upregulated in CRC and predicted poor survival. In addition, circ-ATAD1 was inversely correlated with mature miR-618 but not premature miR-618. In CRC cells, circ-ATAD1 overexpression decreased the level of mature miR-618 but not premature miR-618. Circ-ATAD1 was detected in both the nucleus and cytoplasm. A direct interaction between circ-ATAD1 and miR-618 was observed. Moreover, circ-ATAD1 overexpression reduced the inhibitory effects of miR-618 overexpression on cell proliferation. CONCLUSION: Circ-ATAD1 is overexpressed in CRC and may suppress miR-618 maturation to participate in CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
10.
Sci Total Environ ; : 155572, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525367

RESUMO

Synthesis of carbon material from low-cost and sustainable precursors has been intensively explored in recent years. In this study, a nitrogen (N)-enriched hydrochar was developed via a facile one-step hydrothermal carbonization (HTC) of corn stalk (CS) with liquid digestate (LD) of food waste. The LD substituted water and functioned as the N precursor during HTC. The physicochemical properties of hydrochar derived at different HTC temperatures (180-300 °C) were examined and the reaction mechanism was investigated. Intermolecular dehydration and condensation were the primary reactions in the HTC process of CS without LD. The CS-chars maintained the original structure and morphology of the raw corn stalk. The ammonia and inorganic salts in LD promoted the lignin removal, and accelerated the cleavage of the glycosidic linkages of the polysaccharide and hydrogen bonds of cellulose. Benefited from the ammonia and metals in the LD, the recalcitrance structure of the corn stalk was disrupted during the co-HTC even at a low temperature of 220 °C. Moreover, carbon spheres were observed in the LDCS-chars, indicating the LDCS-chars were resulted from sequential hydrolysis, dehydration and condensation during co-HTC reactions. Reactions between N compounds in the LD and derivatives from CS contributed to N doping. The N content of LDCS-chars achieved 4.95% at 260 °C and 83.94% of the N was presented as pyridinic-N. Co-hydrothermal treatment of CS and LD not only enhanced the characteristics of hydrochar, but also recovered two-thirds of ammoniacal N from the digestate to reduce greenhouse gas emission.

11.
Front Cardiovasc Med ; 9: 864366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514438

RESUMO

Background: Heart failure with improved left ventricular ejection fraction (HFiEF) is linked to a good clinical outcome. The purpose of this study was to create an easy-to-use model to predict the occurrence of HFiEF in patients with heart failure (HF), 1 year after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) (CTO PCI). Methods: Patients diagnosed with HF who successfully underwent CTO PCI between January 2016 and August 2019 were included. To mitigate the effect of residual stenosis on left ventricular (LV) function, we excluded patients with severe residual stenosis, as quantitatively measured by a residual synergy between PCI with Taxus and Cardiac Surgery score (rSS) of >8. We gathered demographic data, medical history, angiographic and procedural characteristics, echocardiographic parameters, laboratory results, and medication information. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression models were used to identify predictors of HFiEF 1 year after CTO revascularization. A nomogram was established and validated according to the area under the receiver operating characteristic curve (AUC) and calibration curves. Internal validation was performed using bootstrap resampling. Results: A total of 465 patients were finally included in this study, and 165 (35.5%) patients experienced HFiEF 1 year after successful CTO PCI. According to the LASSO regression and multivariate logistic regression analyses, four variables were selected for the final prediction model: age [odds ratio (OR): 0.969; 95% confidence interval (CI): 0.952-0.988; p = 0.001], previous myocardial infarction (OR: 0.533; 95% CI: 0.357-0.796; p = 0.002), left ventricular end-diastolic dimension (OR: 0.940; 95% CI: 0.910-0.972; p < 0.001), and sodium glucose cotransporter two inhibitors (OR: 5.634; 95% CI: 1.756-18.080; p = 0.004). A nomogram was constructed to present the results. The C-index of the model was 0.666 (95% CI, 0.613-0.719) and 0.656 after validation. The calibration curve demonstrated that the nomogram agreed with the actual observations. Conclusions: We developed an simple and effective nomogram for predicting the occurrence of HFiEF in patients with HF, 1 year after successful CTO PCI without severe residual stenosis.

12.
Org Biomol Chem ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522070

RESUMO

We describe here a Ni-catalysed deamidative fluorination of diverse amides with electrophilic fluorinating reagents. Different types of amides including aromatic amides and olefinic amides were well compatible, affording the corresponding acyl fluorides in good to excellent yields.

13.
Front Oncol ; 12: 844477, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494070

RESUMO

Casein kinase 1δ/ϵ (CK1δ/ϵ) are well-established positive modulators of the Wnt/ß-catenin signaling pathway. However, the molecular mechanisms involved in the regulation of ß-catenin transcriptional activity by CK1δ/ϵ remain unclear. In this study, we found that CK1δ/ϵ could enhance ß-catenin-mediated transcription through regulating ß-catenin acetylation. CK1δ/ϵ interacted with Tip60 and facilitated the recruitment of Tip60 to ß-catenin complex, resulting in increasing ß-catenin acetylation at K49. Importantly, Tip60 significantly enhanced the SuperTopFlash reporter activity induced by CK1δ/ϵ or/and ß-catenin. Furthermore, a CK1δ/CK1ϵ/ß-catenin/Tip60 complex was detected in colon cancer cells. Simultaneous knockdown of CK1δ and CK1ϵ significantly attenuated the interaction between ß-catenin and Tip60. Notably, inhibition of CK1δ/ϵ or Tip60, with shRNA or small molecular inhibitors downregulated the level of ß-catenin acetylation at K49 in colon cancer cells. Finally, combined treatment with CK1 inhibitor SR3029 and Tip60 inhibitor MG149 had more potent inhibitory effect on ß-catenin acetylation, the transcription of Wnt target genes and the viability and proliferation in colon cancer cells. Taken together, our results revealed that the transcriptional activity of ß-catenin could be modulated by the CK1δ/ϵ-ß-catenin-Tip60 axis, which may be a potential therapeutic target for colon cancer.

14.
Int Orthop ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35384469

RESUMO

PURPOSE: Severe acetabular bone defect is challenging in revision hip arthroplasty. In the present study, we aimed to present new treatment options with the 3D printing technique and analyze the clinical and radiographic outcomes of 3D-printed titanium implants for the treatment of severe acetabular bone defects in revision hip arthroplasty. METHODS: A total of 35 patients with Paprosky type 3 bone defect and pelvic discontinuity (PD), who underwent hip revisions using 3D-printed titanium implants between 2016 and 2019 at our institution, were retrospectively reviewed. Patient-specific 3D-printed titanium augments and shells (strategy A) were used in 22 type 3A and two type 3B patients. Custom 3D-printed flanged components (strategy B) were used in 11 type 3B patients, including five PD. The clinical outcomes were evaluated with the Harris hip score (HHS). In addition, radiographic results were analyzed by the hip centre of rotation (V-COR and H-COR), implant failure, and survivorship. RESULTS: The mean follow-up was 41.5 months (range, 16-62). The HHS was improved from 47.8 ± 8.2 pre-operatively to 78.1 ± 10.1 at one year follow-up and 86.4 ± 5.1 at the last follow-up (p < 0.01). Post-operative V-COR and H-COR of the operated side were 20.8 ± 2.0 mm and 30.2 ± 1.6 mm compared with 51.4 ± 4.1 mm and 33.9 ± 9.0 mm pre-operatively (p < 0.01). The complications included one dislocation and one partial palsy of the sciatic nerve. At the latest follow-up, no radiological component loosening or screw breakage was present. CONCLUSIONS: 3D-printed titanium implants showed satisfactory short- and mid-term clinical and radiographic outcomes. It was an effective therapeutic regimen with a low rate of complications, providing a patient-specific and reliable strategy for the severe acetabular bone defect in revision hip arthroplasty.

15.
Medicine (Baltimore) ; 101(7): e28656, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363160

RESUMO

RATIONALE: The clinical manifestations in patients with disseminated tuberculosis (TB) are nonspecific and may present challenges for early diagnosis. PATIENT CONCERNS AND DIAGNOSES: We describe the case of a 44-year-old man who presented with abdominal pain and discomfort for more than a month. He had undergone surgery for a chest wall abscess 9 months ago. Computed tomography scans showed a miliary pattern in the lung and multiple abscesses in the liver, spleen, left psoas major muscle, skin, and soft tissue, with rim enhancement. Mycobacterium tuberculosis was detected in the drainage fluid of the abscesses and surgical slices, and disseminated TB was diagnosed. INTERVENTIONS AND OUTCOMES: With anti-tuberculosis therapy, the abscesses were gradually absorbed and all cultures were negative. LESSONS: The patient exemplifies the difficulty of the early diagnosis of disseminated TB. Disseminated TB should be considered first in patients with multisystem illness, and then evidence should be pursued relentlessly to establish a diagnosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Miliar , Abscesso , Adulto , Diagnóstico Tardio , Humanos , Masculino , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico
16.
Sci Total Environ ; 833: 155198, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35427627

RESUMO

Microplastics (MPs) have been detected in drinking water, seafood, and commodities relevant to human daily life, causing widespread concern. Although there have been studies on the health risks of MPs to mammals, the impact of MPs on populations with intestinal immune imbalance has been greatly ignored. The vulnerability of the body with intestinal immune imbalance may increase the likelihood of its response to MPs, which is in urgent need of relevant research. Here, we compared the effects of 500 µg/L polystyrene microplastics (PSMPs) on healthy mice and mice with intestinal immune imbalance through colon photographs, histopathological analysis, expression of inflammatory cytokines, PSMPs distribution, microbial community analysis, and metabolomics analysis. The results demonstrated that intestinal immune imbalance aggravated the colonic response to PSMPs. PSMPs exposure significantly increased the expression of inflammation factors (TNF-α, IL-1ß and IFN-γ) in mice with intestinal immune imbalance. In addition, the exposure of PSMPs aggravated the histopathological damage of colonic mucosa in mice with intestinal immune imbalance, and exerted great disturbance on the colonic microbial community and metabolism. This may be due to the significant increase of PSMPs accumulation owing to the damage of intestinal barrier in mice with intestinal immune imbalance. In addition, the increase of several pathogenic bacteria including Bacteroides caused by intestinal immune imbalance also increased the toxicity of PSMPs. Our results highlight that individual with intestinal immune imbalance could be more sensitive to environmental pollution, which should be considered during health risk assessment.

17.
Front Immunol ; 13: 864956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422798

RESUMO

Autoimmune uveitis is a major cause of vision loss and glucocorticoids are major traditional medications, which may induce serious complications. Rapamycin has been demonstrated to exhibit immunosuppressive effects and is promising to be used in treating uveitis by intravitreal injection. However, repeated and frequent intravitreal injections increase the risk of severe ocular complications, while the efficacy of subconjunctival injection of rapamycin is low since it is difficult for rapamycin to penetrate eyeball. Recently, small extracellular vesicles (sEVs) have attracted considerable research interest as natural drug delivery systems that can efficiently cross tissues and biological membranes. SEVs derived from mesenchymal stem cells (MSC-sEVs) also can exert immunosuppressive effect and ameliorate experimental autoimmune uveitis (EAU). The aim of this study was to construct a Rapamycin-loaded MSC-sEVs delivery system (Rapa-sEVs) and investigate its therapeutic effect on EAU by subconjunctival injection. Rapa-sEVs were prepared by sonication and characterized by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Clinical and histological scores were obtained to assess the treatment efficacy. Additionally, T cell infiltration was evaluated by flow cytometry. The results indicated that Rapa-sEVs could reach the retinal foci after subconjunctival injection. Compared to sEVs and rapamycin alone, Rapa-sEVs can produce a more marked therapeutic effect and reduce ocular inflammatory cell infiltration. Overall, MSC-sEVs have significant potential for the delivery of rapamycin to treat EAU. Subconjunctival injection of Rapa-sEVs may be contender for efficacious steroid-sparing immunomodulatory therapy.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Uveíte , Vesículas Extracelulares/patologia , Humanos , Imunomodulação , Células-Tronco Mesenquimais/patologia , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Uveíte/tratamento farmacológico
18.
Plants (Basel) ; 11(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35406941

RESUMO

Cucumbers (Cucumis sativus L.) originated from the South Asian subcontinent, and most of them are fragile to cold stress. In this study, we evaluated the cold tolerance of 115 cucumber accessions and screened out 10 accessions showing high resistance to cold stress. We measured and compared plant hormone contents between cold-tolerant cucumber CT90R and cold-sensitive cucumber CT57S in cold treatment. Most of the detected plant hormones showed significantly higher content in CT90R. To elucidate the role of plant hormones, we compared the leaf- and root-transcriptomes of CT90R with those of CT57S in cold stress treatment. In leaves, there were 1209 differentially expressed genes (DEGs) between CT90R and CT57S, while there were 703 in roots. These DEGs were not evenly distributed across the chromosomes and there were significant enrichments at particular positions, including qLTT6.2, a known QTL controlling cucumber cold tolerance. The GO and KEGG enrichment analysis showed that there was a significant difference in the pathway of plant hormone transductions between CT90R and CT57S in leaves. In short, genes involved in plant hormone transductions showed lower transcription levels in CT90R. In roots, the most significantly different pathway was phenylpropanoid biosynthesis. CT90R seemed to actively accumulate more monolignols by upregulating cinnamyl-alcohol&nbsp;dehydrogenase (CAD) genes. These results above suggest a new perspective on the regulation mechanism of cold tolerance in cucumbers.

19.
Glob Chang Biol ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35447006

RESUMO

Theory and experiments support that plant invasions largely impact aboveground biodiversity and function. Yet, much less is known on the influence of plant invasions on the structure and function of the soil microbiome of coastal wetlands, one of the largest major reservoirs of biodiversity and carbon on Earth. We studied the continental-scale invasion of Spartina alterniflora across 2451 km of Chinese coastlines as our model-system and found that S. alterniflora invasion can largely influence the soil microbiome (across six depths from 0 to 100 cm), compared with the most common microhabitat found before invasion (mudflats, Mud). In detail, S. alterniflora invasion was not only positively associated with bacterial richness but also resulted in important biotic homogenization of bacterial communities, suggesting that plant invasion can lead to important continental scale trade-offs in the soil microbiome. We found that plant invasion changed the community composition of soil bacterial communities across the soil profile. Moreover, the bacterial communities associated with S. alterniflora invasions where less responsive to climatic changes than those in native Mud microhabitats, suggesting that these new microbial communities might become more dominant under climate change. Plant invasion also resulted in important reductions in the complexity and stability of microbial networks, decoupling the associations between microbes and carbon pools. Taken together, our results indicated that plant invasions can largely influence the microbiome of coastal wetlands at the scale of China, representing the first continental-scale example on how plant invasions can reshuffle the soil microbiome, with consequences for the myriad of functions that they support.

20.
Phytomedicine ; 101: 154093, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35447422

RESUMO

BACKGROUND: Heart failure (HF) is a leading cause of death worldwide. Nuanxinkang (NXK) is an effective Chinese herbal formula used in treating HF, but its underlying potential mechanisms have not been fully elucidated. PURPOSE: To explore the protective activities of NXK in ischemia/reperfusion (IR)-induced HF through modulating the ratio of proinflammatory (M1) and anti-inflammatory (M2) macrophage populations and leading to the alleviation of inflammation. MATERIALS AND METHODS: In vivo, mice were subjected to myocardial IR to generate HF mouse models. Mice in the NXK group were treated with NXK for 28 days. Cardiac function was detected by echocardiography. Major lesions on mouse hearts were determined by hematoxylin-eosin (HE) staining, Masson staining, and TUNEL staining. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and qPCR examination. Flow cytometric analyses and qPCR examination were utilized for monitoring the temporal dynamics of macrophage infiltration following IR. In vitro, two polarized models were established by stimulating RAW264.7 cells with 200 ng/ml lipopolysaccharide (LPS) or 20 ng/ml interleukin-4 (IL-4). The RAW264.7 cells with nuclear factor-κB (NF-κB) overexpression was generated by transient transfection of NF-κB plasmids, and NXK intervention was conducted on this cell model to further clarify the involvement of NF-κB signaling in the NXK-mediated HF process. RESULTS: In the present study, NXK was found to significantly contribute the cardiac function and ameliorate cardiac fibrosis and apoptosis after myocardial IR injury in vivo, which may be partially due to a decrease in inflammation. We therefore hypothesized that NXK reduced inflammatory damage by modulating subtypes of macrophages. And the results demonstrated that the percentage of proinflammatory macrophages infiltrated in the post-IR period was reduced with NXK treatment, and thereby blunting the wave of proinflammatory response and shifting the peak of the anti-inflammatory macrophage-mediated wound healing process towards an earlier time point. The further investigation showed that macrophage polarization was mediated by NXK through inhibiting the phosphorylation and the nuclear translocation of NF-κB. Besides, the phosphorylated IKKß and IκBα, upstream mediators of the NF-κB pathway, also decreased by NXK. Moreover, the overexpression of NF-κB partially reversed the NXK-induced favorable activities; and successfully compensated the suppressive effect on inflammation and the phosphorylation of NF-κB. CONCLUSION: In conclude, our results demonstrated that NXK induced the cardioprotective effects against IR injury through a regulatory axis of IKKß/IκBα/NF-κB-mediated macrophage polarization. The information gained from this study provide a possible natural strategy for anti-inflammatory treatment of HF.

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