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1.
Brain Imaging Behav ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619646

RESUMO

Diffusive and progressive tumor infiltration within language-related areas of the brain induces functional reorganization. However, the macrostructural basis of subsequent language deficits is less clear. To address this issue, lesion topography data from 137 preoperative patients with left cerebral language-network gliomas (81 low-grade gliomas and 56 high-grade gliomas), were adopted for multivariate machine-learning-based lesion-language mapping analysis. We found that tumor location in the left posterior middle temporal gyrus-a bottleneck where both dorsal and ventral language pathways travel-predicted deficits of spontaneous speech (cluster size = 1356 mm3, false discovery rate corrected P < 0.05) and naming scores (cluster size = 1491 mm3, false discovery rate corrected P < 0.05) in the high-grade glioma group. In contrast, no significant lesion-language mapping results were observed in the low-grade glioma group, suggesting a large functional reorganization. These findings suggest that in patients with gliomas, the macrostructural plasticity mechanisms that modulate brain-behavior relationships depend on glioma grade.

2.
Biomater Sci ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33605949

RESUMO

Non-viral gene delivery vectors with high transfection efficiency both in vitro and in vivo and low cytotoxicity are highly desirable for clinical applications. Herein, a series of guanidine-rich polypeptides bearing hydrophobic amino acid pendants was efficiently prepared via the 1,3-dipolar cycloaddition between azido decorated polypeptide and propargyl functionalized guanidinium and N-acetylamino acids. CD analysis indicated α-helical conformations of all resulting polypeptides in aqueous solution. The guanidine-rich polypeptide/DNA complexes showed significantly enhanced cellular internalization and high cell viability (>90%) in different mammalian cell lines (i.e., HeLa and RAW 264.7) at concentrations of the best performance. The top-performing guanidine-rich polypeptide containing 10% N-acetyl-l-valine pendants outperformed the commercial transfection reagent PEI by 400 times in vitro and 6 times in vivo. This study provides a new guidance for future molecular design of non-viral gene vectors with high delivery efficiency and low cytotoxicity.

3.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33537823

RESUMO

Osteosarcoma (OS) is a musculoskeletal malignancy that originates from interstitial cells. An increasing number of studies have verified that long non­coding RNAs (lncRNAs) participate in the progression of numerous types of cancer. It has been reported that LINC00467 is a cancer­promoting gene in some types of cancer; however, the regulatory mechanism of LINC00467 in OS remains unknown. In the present study, reverse transcription-quantitative PCR was used to determine LINC00467 expression in OS tissues and cells. Additionally, the impact of LINC00467­knockdown on OS cell proliferation, migration and invasion was analyzed using Cell Counting Kit­8, colony formation and Transwell assays, as well as western blot analysis. RNA pulldown and luciferase reporter assays were conducted to investigate the regulatory mechanism of LINC00467 in OS. The results delineated that LINC00467 expression was elevated in OS tissues and cells, and that high LINC00467 expression was associated with a poor prognosis in patients with OS. LINC00467 inhibition suppressed OS progression by inhibiting cell proliferation, migration, invasion and epithelial­mesenchymal transition. LINC00467 served as a molecular sponge for microRNA (miR)­217, while karyopherin subunit α4 (KPNA4) was a downstream target gene of miR­217. Moreover, the overexpression of KPNA4 reversed the inhibitory effects of LINC00467 inhibition on OS progression. Therefore, the present study elucidated the potential mechanism of LINC00467 in OS and indicated that LINC00467 exerted its carcinogenic effects on OS through the miR­217/KPNA4 axis, implying that LINC00467 may be a novel potential therapeutic target for OS.

5.
Cell Biol Int ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527608

RESUMO

Mental retardation is the main clinical manifestation of Down syndrome (DS), and neural abnormalities occur during the early embryonic period and continue throughout life. Tc1, a model mouse for DS, carries the majority part of the human chromosome 21 and has multiple neuropathy phenotypes similar to patients with DS. To explore the mechanism of early neural abnormalities of Tc1 mouse, induced pluripotent stem (iPS) cells from Tc1 were obtained, and genome-wide gene expression and methylation analysis were performed for Tc1 and wild type mouse iPS cells. Our results showed hyper-methylation profiles for Tc1 iPS cells, and the abnormal genes were shown to be related to neurodevelopment and distributed on multiple chromosomes. In addition, important genes involved in neurogenesis and neurodevelopment were shown to be down-regulated in Tc1 iPS cells. In short, our study indicated that genome-wide hyper-methylation leads to disordered expression of genes associated with neurodevelopmental in the early development in Tc1mouse. Overall, our work provided a useful reference for the study of molecular mechanism of nervous system abnormalities in DS. This article is protected by copyright. All rights reserved.

6.
Clin Nutr ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33583658

RESUMO

BACKGROUND: The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes. METHODS: Overweight patients (body mass index (BMI) ≥23 kg/m2) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery. RESULTS: A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m2). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis. CONCLUSION: Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols.

7.
Food Chem ; 349: 129166, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33550019

RESUMO

Grafting copolymerization of phenolic acids onto polysaccharides is an important strategy to improve their biological activities. In this study, ferulic acid (FA)-grafted carboxylic curdlan conjugates, namely, Cur-8-g-FA, Cur-24-g-FA, and Cur-48-g-FA, were synthesized by free radical-induced grafting. Results showed that FA was covalently grafted onto carboxylic curdlans via ester bonds. The grafting ratios of Cur-8-g-FA, Cur-24-g-FA, and Cur-48-g-FA were 223.03 ± 12.63, 115.63 ± 5.96, and 152.30 ± 4.57 mg FA/g, respectively, which were related with the carboxylate contents, molecular weights, and chain conformations of carboxylic curdlans. Compared with carboxylic curdlans, the FA-grafted carboxylic curdlan conjugates had lower thermal stability, molecular weight, and rheological property and looser surface morphology but had more prominent antioxidant benefits in vitro, which were proportional to their grafting ratios. Moreover, good storage stability against chemical degradation was exhibited by the ß-carotene in Pickering emulsions stabilized by Cur-8-g-FA with a high grafting ratio and molecular weight.

8.
Nutrition ; 86: 111156, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33601124

RESUMO

OBJECTIVES: We investigated whether measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia, as defined by the new European Working Group on Sarcopenia in Older People 2 consensus. METHODS: We conducted a prospective study of patients who underwent a radical gastrectomy for gastric cancer between August 2014 and June 2019. Muscle strength was measured using a handgrip dynamometer. Computed tomography images at the third lumbar vertebra level were used to assess muscle quantity and quality by the measuring cross-sectional muscle area and mean muscle attenuation, respectively. Probable sarcopenia was defined by low muscle strength. Sarcopenia was diagnosed by additional low muscle quantity or quality. Clinical outcomes were obtained by prospective data collection and follow up. RESULTS: Probable sarcopenia was identified in 419 patients, including 285 patients with sarcopenia. Patients with sarcopenia had a higher incidence of postoperative complications, higher costs, longer length of postoperative hospital stay, and worse overall survival (OS) and disease-free survival (DFS) compared with patients with low muscle strength only. The multivariate logistic analysis showed that sarcopenia and hypoproteinemia were independent risk factors for postoperative complications in patients with probable sarcopenia. Moreover, multivariate Cox analyses showed that sarcopenia remained an independent risk factor for OS and DFS in patients with probable sarcopenia. CONCLUSIONS: The measurement of muscle quantity/quality has additional predictive value for postoperative complications, OS, and DFS after gastrectomy for gastric cancer in patients with probable sarcopenia.

9.
Sci Rep ; 11(1): 2918, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536546

RESUMO

Lipopolysaccharide (LPS) could induce apoptosis and dysfunction of endothelial cells. We aimed to reveal the effects of macrophages on cell proliferation and apoptosis in LPS induced human umbilical vein endothelial cells (HUVECs). THP-1 derived macrophages and HUVECs were co-cultured in the presence of LPS. Cell viability was measured by Cell Counting Kit-8 and apoptosis was analyzed by flow cytometry. Expression of Ang1, the NF-κB component p65 was evaluated by western blot and quantitative PCR. Small interfering RNAs (siRNAs) were used to knockdown the expression of proinflammatory cytokines and p65 in HUVECs. Plasmid transfection-mediated overexpression of Ang1 was employed to see its effects on cell proliferation and apoptosis in HUVECs. Macrophages enhanced LPS-induced proliferation impairments and apoptosis in HUVECs, which could be attenuated by siRNA-mediated knockdown of cytokines TNF-α, IL-1ß, IL-6 and IL-12p70 in macrophages. The dysfunction of HUVECs was tightly associated with reduced Ang1 expression and increased phosphorylated p65 (p-65). Overexpression of Ang1 in HUVECs significantly decreased p-p65, suggesting negatively regulation of p-p65 by Ang1. Overexpression of Ang1, adding recombinant Ang1 or silencing of p65 substantially attenuated the dysfunction of HUVECs in terms of cell proliferation and apoptosis. In conclusions, THP-1-derived macrophages enhance LPS induced dysfunction of HUVECs via Ang1 and NF-κB pathways, suggesting new therapeutic targets for sepsis.

10.
Med Sci Monit ; 27: e928022, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33550326

RESUMO

BACKGROUND The aim of this study was to compare the clinical and radiological outcomes of the 3D-printed artificial vertebral body vs the titanium mesh cage in repairing bone defects for single-level anterior cervical corpectomy and fusion (ACCF). MATERIAL AND METHODS A total of 51 consecutive patients who underwent single-level ACCF in Huai'an Second People's Hospital from July 2017 to August 2020 were retrospectively reviewed. According to the implant materials used, patients were divided into a 3D-printed artificial vertebral body group (3D-printed group) (n=20; 12 males, 8 females) and a titanium mesh cage group (TMC group) (n=31; 15 males, 16 females). General data, radiological parameters, and clinical outcomes were recorded. RESULTS The rate of subsidence in the 3D-printed group (0.01, 2/20) was lower than in the TMC group (0.29, 9/31) (P<0.05). HAE and HPE of the patients in the 3D-printed group were significantly higher than those in the TMC group (P<0.05). C2-C7 Cobb angle and SA of the patients in the 3D-printed group were significantly larger than those in the TMC group (P<0.05). All patients in the 2 groups showed significant improvement in VAS, JOA, and NDI scores at 3 months and 1 year after surgery. CONCLUSIONS 3D-printed artificial vertebral body helps maintain intervertebral height and cervical physiological curvature and is a good candidate for ACCF.

11.
BMC Cardiovasc Disord ; 21(1): 84, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568060

RESUMO

BACKGROUND: The ablation targets of atrial fibrillation (AF) are adjacent to bronchi and pulmonary arteries (PAs). We used computed tomography (CT) to evaluate the anatomical correlation between left atrium (LA)-pulmonary vein (PV) and adjacent structures. METHODS: Data were collected from 126 consecutive patients using coronary artery CT angiography. The LA roof was divided into three layers and nine points. The minimal spatial distances from the nine points and four PV orifices to the adjacent bronchi and PAs were measured. The distances from the PV orifices to the nearest contact points of the PVs, bronchi, and PAs were measured. RESULTS: The anterior points of the LA roof were farther to the bronchi than the middle or posterior points. The distances from the nine points to the PAs were shorter than those to the bronchi (5.19 ± 3.33 mm vs 8.62 ± 3.07 mm; P < .001). The bilateral superior PV orifices, especially the right superior PV orifices were closer to the PAs than the inferior PV orifices (left superior PV: 7.59 ± 4.14 mm; right superior PV: 4.43 ± 2.51 mm; left inferior PV: 24.74 ± 5.26 mm; right inferior PV: 22.33 ± 4.75 mm) (P < .001). CONCLUSIONS: The right superior PV orifices were closer to the bronchi and PAs than other PV orifices. The ablation at the mid-posterior LA roof had a higher possibility to damage bronchi. CT is a feasible method to assess the anatomical adjacency in vivo, which might provide guidance for AF ablation.

12.
Cancer Cell Int ; 21(1): 71, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482821

RESUMO

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

13.
Soft Matter ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514979

RESUMO

Dissolution and dissociation of CO2 in an aqueous phase induce diffusiophoretic motion of suspended particles with a nonzero surface charge. We report CO2-driven diffusiophoresis of colloidal particles and bacterial cells in a circular Hele-Shaw geometry. Combining experiments and model calculations, we identify the characteristic length and time scales of CO2-driven diffusiophoresis in relation to system dimensions and CO2 diffusivity. The motion of colloidal particles driven by a CO2 gradient is characterized by measuring the average velocities of particles as a function of distance from the CO2 sources. In the same geometrical configurations, we demonstrate that the directional migration of wild-type V. cholerae and a mutant lacking flagella, as well as S. aureus and P. aeruginosa, near a dissolving CO2 source is diffusiophoresis, not chemotaxis. Such a directional response of the cells to CO2 (or an ion) concentration gradient shows that diffusiophoresis of bacteria is achieved independent of cell shape, motility and the Gram stain (cell surface structure). Long-time experiments suggest potential applications for bacterial diffusiophoresis to cleaning systems or anti-biofouling surfaces, by reducing the population of the cells near CO2 sources.

14.
Nutr Neurosci ; : 1-14, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494658

RESUMO

BACKGROUND: Homocysteine (Hcy) and folate, involved in a common metabolic pathway supplying essential methyl groups for DNA and protein synthesis, have been found to be associated with cognitive function. Moreover, diet may influence methionine cycle metabolites (MCM) as well as mild cognitive impairment (MCI), but MCM-related dietary patterns are unclear in an older population. OBJECTIVE: The study aimed to identify MCM-related dietary patterns of older Chinese adults, and examine their association with the prevalence of MCI in a large population-based study. METHODS: This study included 4457 participants ≥ 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. Dietary data were collected using a valid self-administered food frequency questionnaire, and factor analysis was used to identify major dietary patterns in the population. MCM-based dietary patterns were derived using reduced rank regression (RRR) based on serum folate and Hcy as response variables. RESULTS: Compared with the participants in the lowest quartile of vegetarian pattern and processed foods pattern, the odds ratios (ORs) of MCI in the highest quartile were 0.72 (95% CI 0.53-0.98) and 1.39 (95% CI 1.03-1.88), respectively. In the MCM-based dietary patterns derived using RRR, the ORs for MCI for the highest quartile of MCM patterns I and II were 0.58 (95% CI 0.44-0.78) and 1.38 (95% CI 1.04-1.83), respectively, compared with participants in the lower quartile. CONCLUSIONS: Findings from this large population-based study suggested that adopting an MCM-related dietary pattern, especially avoiding processed foods, can decrease the occurrence of MCI.

15.
J Neurointerv Surg ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472873

RESUMO

BACKGROUND: Intracranial aneurysms (IAs) are common in the population and current imaging-based rupture risk assessment needs to be refined. We aimed to use four-dimensional CT angiography (4D-CTA) to investigate the associations of irregular pulsation of IAs with conventional risk factors and the estimated rupture risk. METHODS: One hundred and five patients with 117 asymptomatic IAs underwent 4D-CTA. Geometric and morphologic parameters were measured and the presence of irregular pulsation (defined as a temporary focal protuberance ≥1 mm on more than three successive frames) was identified on 4D-CTA movies. One- and 5 year aneurysm rupture risk were estimated using UCAS and PHASES calculators. Univariate and multivariate analyses were performed to investigate the conventional risk factors associated with irregular pulsation. RESULTS: Irregular pulsation was observed in 41.0% (48/117) of IAs. Aneurysm size (OR=1.380, 95% CI 1.165 to 1.634), irregular shape (OR=3.737, 95% CI 1.108 to 12.608), and internal carotid artery location (OR=0.151, 95% CI 0.056 to 0.403) were independently associated with irregular pulsation (P<0.05). Aneurysms with irregular pulsation had more than a 6-fold higher estimated rupture risk (1- and 5-year risk [95% CI], 1.56% [0.42%-3.91%], and 2.40% [1.30%-4.30%], respectively) than aneurysms without irregular pulsation (0.23% [0.14%-0.78%] and 0.40% [0.40%-1.30%], respectively) (P<0.001). CONCLUSIONS: IAs with irregular pulsation are associated with larger size, irregular-shape, and non-ICA origin, and have more than a 6-fold higher estimated 1- and 5-year rupture risk than aneurysms without irregular pulsation. Irregular pulsation should be validated in future longitudinal studies to determine its predictive value for aneurysm growth and rupture.

16.
Cell Res ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473154

RESUMO

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal-distal and anterior-posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

17.
Phys Biol ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33462162

RESUMO

Bacterial biofilms are communities of bacteria that exist as aggregates that can adhere to surfaces or be free-standing. This complex, social mode of cellular organization is fundamental to the physiology of microbes and often exhibits surprising behaviour. Bacterial biofilms are more than the sum of their parts: Single cell behaviour has a complex relation to collective community behaviour, in a manner perhaps cognate to the complex relation between atomic physics and condensed matter physics. Biofilm microbiology is a relatively young field by biology standards, but it has already attracted intense attention from physicists. Sometimes, this attention takes the form of seeing biofilms as inspiration for new physics. In this roadmap, we highlight the work of those who have taken the opposite strategy: We highlight work of physicists and physical scientists who use physics to engage fundamental concepts in bacterial biofilm microbiology, including adhesion, sensing, motility, signalling, memory, energy flow, community formation and cooperativity. These contributions are juxtaposed with microbiologists who have made recent important discoveries on bacterial biofilms using state-of-the-art physical methods. The contributions to this roadmap exemplify how well physics and biology can be combined to achieve a new synthesis, rather than just a division of labour.

18.
Int J Med Sci ; 18(1): 169-175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390785

RESUMO

Hepatocellular carcinoma (HCC) is known as the fifth most common cancer in the world for its poor prognosis. New diagnostic markers and treatments are urgent to discover. To evaluate the protein expression of Tropomyosin4 (TPM4) and investigate its prognostic value in HCC, we collected 110 patients with different degrees of HCC and 10 patients with normal hepatic tissues and performed immunohistochemistry. Western bot was used to evaluate the expression of TPM4 in three HCC cell lines (HepG2, Huh7, SMMC-7721) and normal liver cell line LO2, as well as 7 HCC tissues and 7 normal hepatic tissues. The results of TPM4 staining revealed that TPM4 expression in HCC was higher than that in normal hepatic tissues, which was positive in 51.8% (n=57) and negative in 48.2% (n=53) while in normal hepatic tissues positive staining was in 10% (n=1) and negative staining was in 90% (n=9) (P=0.011). And the expression of TPM4 was related to pT status, grade and stage (P<0.001, P=0.015 and P<0.001, respectively). Western blot results indicated that TPM4 was high expressed in HCC cell line and HCC tissues. In conclusion, we believe that TPM4 can be applied as a diagnostic and prognostic marker to assist the management of HCC.

19.
J Mol Histol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33387144

RESUMO

Evidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1ß in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1ß in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of ß-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating ß-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting ß-catenin and activating YAP signaling. In addition, this study provided evidences that activation of ß-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33406237

RESUMO

OBJECTIVES: Ceftriaxone is currently the last-remaining empirical antimicrobial therapy for treatment of gonorrhoea. However, the high-level ceftriaxone-resistant gonococcal FC428 clone has shown transmission in China in recent years. Therefore, the aim of this study was to analyse ceftriaxone resistance among a collection of recent clinical isolates, with a specific focus on prevalence of the FC428 clone. METHODS: A total of 70 consecutive gonococcal isolates were collected between May and October 2019 from a single hospital in Hangzhou, China, and analysed for antimicrobial susceptibility by the agar dilution method. STs were determined by PCR and sequences and isolates related to the FC428 clone were further characterized by WGS and phylogenetic analysis. RESULTS: Ceftriaxone resistance (MIC >0.125 mg/L) was observed in 21 (30%) isolates, while 14 (20%) isolates displayed a ceftriaxone MIC of 0.125 mg/L. Importantly, seven (10%) isolates were related to the gonococcal FC428 clone based on the presence of mosaic penA allele 60.001, displaying identical or closely related STs, and phylogenetic analysis after WGS. These seven isolates displayed high-level ceftriaxone resistance (MIC = 1 mg/L) and all associated gonorrhoea cases resulted in treatment failure because oral cephalosporins were initially prescribed. Subsequent re-treatment with a higher dose (2 g) of IV ceftriaxone appeared to be successful because all patients returning for test-of-cure became culture-negative. CONCLUSIONS: Here, we report a high percentage of the internationally spreading gonococcal FC428 clone among clinical isolates from a single hospital in Hangzhou, China. A high dose of ceftriaxone is currently the only recommended and effective therapy.

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