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2.
Cell Death Differ ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934104

RESUMO

Macrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα-/- macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

3.
J Cell Mol Med ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942984

RESUMO

PIWI-interacting RNAs (piRNAs) are recently discovered small non-coding RNAs consisting of 24-35 nucleotides, usually including a characteristic 5-terminal uridine and an adenosine at position 10. PIWI proteins can specifically bind to the unique structure of the 3' end of piRNAs. In the past, it was thought that piRNAs existed only in the reproductive system, but recently, it was reported that piRNAs are also expressed in several other human tissues with tissue specificity. Growing evidence shows that piRNAs and PIWI proteins are abnormally expressed in various diseases, including cancers, neurodegenerative diseases and ageing, and may be potential biomarkers and therapeutic targets. This review aims to discuss the current research status regarding piRNA biogenetic processes, functions, mechanisms and emerging roles in various diseases.

4.
CNS Neurosci Ther ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942994

RESUMO

AIMS: NOTCH3 gene mutations predominantly cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a common etiology of subcortical vascular dementia (SVaD). Besides, there may be a pathogenic link between NOTCH3 variants and Alzheimer's disease (AD). We aimed to study the role of NOTCH3 variants in AD and SVaD patients. METHODS: We recruited 763 patients with dementia (667 AD and 96 SVaD) and 365 healthy controls from the Southern Han Chinese population. Targeted capture sequencing was performed on NOTCH3 coding and adjacent intron regions to detect the pathogenic variants in AD and SVaD. The relationship between common or rare NOTCH3 variants and AD was further analyzed using Plink1.9. RESULTS: Five known pathogenic variants (p.R182C, p.C201S, p.R544C, p.R607C, and p.R1006C) and two novel likely pathogenic variants (p.C201F and p.C1061F) were detected in 16 SVaD patients. Additionally, no pathogenic or likely pathogenic variants were found in AD patients. NOTCH3 was not associated with AD in either single-variant association analysis or gene-based association analysis. CONCLUSION: Our findings broaden the mutational spectrum of NOTCH3 and validate the pathogenic role of NOTCH3 mutations in SVaD, but do not support the notion that NOTCH3 variation influences the risk of AD.

5.
Front Immunol ; 12: 624360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841405

RESUMO

The gut-liver axis has been increasingly recognized as a major autoimmunity modulator. However, the implications of intestinal barrier in the pathogenesis of autoimmune hepatitis (AIH) remain elusive. Here, we investigated the functional role of gut barrier and intestinal microbiota for hepatic innate immune response in AIH patients and murine models. In this study, we found that AIH patients displayed increased intestinal permeability and pronounced RIP3 activation of liver macrophages. In mice models, intestinal barrier dysfunction increased intestinal bacterial translocation, thus amplifying the hepatic RIP3-mediated innate immune response. Furthermore, GSK872 dampened RIP3 activation and ameliorated the activation and accumulation of liver macrophages in vitro and in vivo experiments. Strikingly, broad-spectrum antibiotic ablation significantly alleviated RIP3 activation and liver injury, highlighting the causal role of intestinal microbiota for disease progression. Our results provided a potentially novel mechanism of immune tolerance breakage in the liver via the gut-liver axis. In addition, we also explored the therapeutic and research potentials of regulating the intestinal microbiota for the therapy of AIH.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33907083

RESUMO

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the accuracy of pedicle screw placement and proximal facet joint violation (FJV) in single-level degenerative lumbar diseases using Cortical bone trajectory (CBT) and traditional trajectory (TT) techniques, and analyzed their possible risk factors. SUMMARY OF BACKGROUND DATA: CBT screws have been utilized increasingly to improve cortical bone contact to prevent screw pullout and reduce approach-related morbidity. However, the studies on intra-pedicular accuracy and proximal FJV between the two methods are rare. METHODS: A total of 40 patients who required single-level instruments were included in the retrospective study treated with the CBT-TLIF and the TT-TLIF at a 1:1 ratio from March 2019 to August 2020. The radiographic outcomes were the intra-pedicular accuracy and proximal FJV. Moreover, the possible risk factors were assessed using bivariate and multivariate analyses. RESULTS: As for the intra-pedicular accuracy, 73 screws (91.3%) were classified as grade A, 7 screws (8.7%) classified as grade B in the CBT group. A total of 71 screws (88.8%) were graded A with remaining 8 screws (10.0%) graded B and 1 screw (1.2%) graded C in the TT group. The proportion of optimal and clinically acceptable screw positions in the two groups were not significantly different (P > 0.05). In addition, the rate of proximal FJV in CBT approach (8.3%) was significantly lower than that in the TT approach (35.0%) (P < 0.001). Multivariate analysis showed the TT insertion approach and facet angle ≥45° were the independent risk factors for proximal FJV, but no factors above affected intra-pedicular accuracy. CONCLUSION: Compared with the TT approach in TLIF, the CBT approach showed similar intra-pedicular accuracy and remarkable superiority in proximal facet joint protection. Facet angle ≥45° is the independent risk factors for proximal FJV.Level of Evidence: 2.

7.
Cancer Control ; 28: 10732748211011951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33910393

RESUMO

PURPOSE: Dedicator of cytokinesis 8 (DOCK8) was reported to have a vital link to immunoregulation. However, the mechanisms by which it drives immune infiltration in cancer remain uncertain. We tried to assess the role of DOCK8 in patients with cancer, especially human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). METHODS: Data on the expression and survival of DOCK8 in patients with various cancers were analyzed using the Oncomine and TIMER databases. The TIMER database assessed the relationship of DOCK8 with immune infiltration levels and various markers of multiple immune cells. Gene set enrichment analysis revealed tumor-associated biological processes related to DOCK8. ENCODE database was used to explore relevant transcription factors of DOCK8, and a PPI network was constructed using GENEMINIA. The expression and survival role of DOCK8 was confirmed in patients from independent GEO datasets. RESULTS: We determined that DOCK8 expression was upregulated or downregulated in various cancers unlike in healthy tissues. A high expression of DOCK8 was significantly correlated with a favorable prognosis in HPV-positive HNSCC and lung adenocarcinoma (LUAD). Furthermore, multivariate Cox regression analysis revealed that DOCK8 was an independent prognostic factor of HPV-positive HNSCC. Additionally, elevated DOCK8 expression was positively correlated with multiple immune cell infiltration levels and immune marker expression associated with particular immune cell subsets. Also, 14 pathways involved in immune activities and carcinogenesis, 22 potential TFs, and co-expression proteins of DOCK8 indicated DOCK8 to be related to tumor-associated biological processes. Ultimately, we verified that DOCK8 is upregulated and confers a favorable overall survival and progression-free survival status in patients with HPV-positive HNSCC. CONCLUSION: These results elucidate that high expression of DOCK8 indicates a favorable prognosis in patients with HPV-positive HNSCC as well as increased microenvironmental immune infiltration levels. It would provide new insights into the prognosis predicting and clinical regimen decision making in patients with HPV-positive HNSCC.

8.
Clin Genet ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33928629

RESUMO

Glanzmann's thrombasthenia (GT) is a severe hemorrhagic disease. It is caused by mutations in ITGA2B or ITGB3, which are the respective genes encoding integrin αIIb and ß3. Despite widespread mutational analysis, the mechanisms underlying the extensive variability in bleeding severity observed among affected individuals remains poorly understood. In order to explore the mechanisms conferring for bleeding heterogeneity, three GT patients with ITGA2B c.2671C > T (p.Q891X) who possessed different bleeding scores were studied. Analysis showed that there was significant difference in nonsense-mediated mRNA decay (NMD) efficiency among the three patients. These differences positively correlated with their bleeding score. Next, a knock-in mouse model (KI mice) with the ITGA2B c.2659C > T (p.Q887X) was generated using CRISPR/Cas9. Importantly, this mutation is homologous to ITGA2B c.2671C > T (p.Q891X) in humans. The bleeding time of KI mice was significantly in comparison to the wide-type mice. Interestingly, bleeding was stopped after treatment with caffeine, which is a known NMD inhibitor. This suggests that NMD efficiency potentially influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) KI mice.

9.
Aging (Albany NY) ; 13(8): 11352-11362, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33833133

RESUMO

BACKGROUND: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. METHOD: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. RESULTS: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). CONCLUSIONS: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.

10.
Chemosphere ; 278: 130436, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33839386

RESUMO

To solve the bottleneck of the unstable accumulation of nitrite in the partial nitrification (PN)-anammox (AMX) in municipal wastewater treatment, a novel process called partial denitrification (PD)-AMX has been developed. PD-AMX, which is known for cost-efficiency and environmental friendliness, has currently exhibited a promising potential for the removal of biological nitrogen from municipal wastewater and has attracted much research interest regarding its process mechanisms, as well as its practical applications. Here, we review the recent advances in the PD process and its coupling to the anammox process, including the development, basic principles, main characteristics, and critical process parameters of the stable operation of the PD-AMX process. We also explore the microbial community and its characteristics in the system and summarize the knowledge of the dominant bacteria to clarify the key factors affecting PD-AMX. Then, we introduce the engineering feasibility and economic feasibility as well as the potential challenges of the process. The induction and implementation of partial denitrification and maintenance of mainstream anammox are critical issues to be urgently solved. Meanwhile, the implementation of a full mainstream anammox application remains burdensome, while the mechanism of partial denitrification coupled to anammox needs to be further studied. Additionally, stable operation performance and process control1 methods need to be optimized or developed for the PD-AMX system for better engineering practice. This review can help to accelerate the research and application of the PD-AMX process for municipal wastewater treatment.

11.
BMC Plant Biol ; 21(1): 164, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794787

RESUMO

BACKGROUND: Diatoms contribute 20% of the global primary production and are adaptable in dynamic environments. Diatoms always bloom earlier in the annual phytoplankton succession instead of dinoflagellates. However, how diatoms acclimate to a dynamic environment, especially under changing light conditions, remains unclear. RESULTS: We compared the growth and photosynthesis under fluctuating light conditions of red tide diatom Skeletonema costatum, red tide dinoflagellate Amphidinium carterae, Prorocentrum donghaiense, Karenia mikimotoi, model diatom Phaeodactylum tricornutum, Thalassiosira pseudonana and model dinoflagellate Dinophycae Symbiodinium. Diatoms grew faster and maintained a consistently higher level of photosynthesis. Diatoms were sensitive to the specific inhibitor of Proton Gradient Regulation 5 (PGR5) depending photosynthetic electron flow, which is a crucial mechanism to protect their photosynthetic apparatus under fluctuating light. In contrast, the dinoflagellates were not sensitive to this inhibitor. Therefore, we investigate how PGR5 functions under light fluctuations in the model diatom P. tricornutum by knocking down and overexpressing PGR5. Overexpression of PGR5 reduced the photosystem I acceptor side limitation (Y (NA)) and increased growth rate under severely fluctuating light in contrast to the knockdown of PGR5. CONCLUSION: Diatoms acclimatize to fluctuating light conditions better than dinoflagellates. PGR5 in diatoms can regulate their photosynthetic electron flow and accelerate their growth under severe light fluctuation, supporting fast biomass accumulation under dynamic environments in pioneer blooms.


Assuntos
Diatomáceas/fisiologia , Dinoflagelados/fisiologia , Regulação da Expressão Gênica/fisiologia , Luz , Fotossíntese , Aclimatação/genética , Diatomáceas/genética , Diatomáceas/crescimento & desenvolvimento , Dinoflagelados/genética , Dinoflagelados/crescimento & desenvolvimento
12.
PLoS One ; 16(3): e0247578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711032

RESUMO

To select the optimum fertilizer application under specific irrigation levels and to provide a reliable fertigation system for tomato plants, an experiment was conducted by using a microporous membrane for water-fertilizer integration under non-pressure gravity. A compound fertilizer (N:P2O5:K2O, 18:7:20) was adopted for topdressing at four levels, 1290 kg/ha, 1140 kg/ha, 990 kg/ha, and 840 kg/ha, and the locally recommended level of 1875 kg/ha was used as the control to explore the effects of different fertilizer application rates on growth, nutrient distribution, quality, yield, and partial factor of productivity (PFP) in tomato. The new regime of microporous membrane water-fertilizer integration under non-pressure gravity irrigation reduced the fertilizer application rate while promoting plant growth in the early and intermediate stages. Except for the 990 kg/ha fertilizer treatment, yields per plant and per plot for each fertilizer application rate were higher than or equal to those of the control. The new regime could effectively improve PFP and reduce soil nutrient enrichment. Fertilizer at 840 kg/ha showed the optimum results by increasing PFP by 75.72% as compared to control. In conclusion, the fertilizer rate at 840 kg/ha has not only maintained the productivity of soil but also tomato growth and quality of fruit which makes the non-pressure gravity irrigation a potential and cost-effective way for fertilizer application.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 254: 119671, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33744698

RESUMO

Terahertz spectral features of alkali halide crystals were studied with the combination of broadband terahertz time-domain spectroscopy and the solid-state-based density functional theory calculations. To understand the particular modes of the observed terahertz features of the alkali halide crystals, the resonant modes of KCl and CsCl were analyzed using face-centered cubic and body-centered cubic lattice models, respectively. The results show that the characteristic terahertz absorption peaks could be assigned to the lattice vibration of the ionic crystals. Furthermore, the terahertz responses of a series of alkali halides were recorded, and obvious absorption peaks were observed in each salt in the frequency region below 8.5 THz. What is more interestingly is that the frequencies of these observed peaks are red-shifted with the increases of the mass and radius of the ions. This correlation between the resonant frequency of the lattice vibration, the reduced atomic mass, and the equilibrium distance between the ions agrees well with the harmonic oscillator model.

14.
Front Immunol ; 12: 630112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643314

RESUMO

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

15.
Environ Res ; 197: 111006, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33722525

RESUMO

Silver (Ag) nanocomposites were prepared via a facile and eco-friendly route using microbial extracellular polymer substances (EPSs) as green substrates for the catalytic reduction of 4-nitrophenol. Batch adsorption experiments demonstrated the binding of microbial EPSs to silver ions (Ag+), which was promoted by UV light, as was evident in the kinetics and thermodynamics analyses. The assembly mechanism of Ag nanocomposites prepared using microbial EPSs in the presence of UV light was investigated using the spectral analysis. The results showed that Ag+ was reduced and transformed into Ag0 by the hemiacetal groups in the microbial EPSs, and that UV light accelerated the nucleation and growth of Ag0 to form Ag nanoparticles (diameter about 12 nm), followed by loading on the surface of microbial EPSs. Catalytic reduction of 4-nitrophenol over Ag nanocomposites was almost completed within 60 s without stirring, and the kinetic rate constant (k) was 49.9 × 10-3 s-1. The recyclability test showed that Ag nanocomposites stably maintained the efficiency of catalytic reduction through five repeated reaction cycles. This work proved that Ag nanocomposites assembled using microbial EPSs have great catalytic activity in the reduction of 4-nitrophenol, providing the green and efficient catalyst for the reduction of organic pollutants in the environment.

16.
Biochem Biophys Res Commun ; 553: 1-8, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33752091

RESUMO

BACKGROUND AND AIMS: Hypercholesterolemia is characterized by the elevation of plasma total cholesterol level, especially low-density lipoprotein (LDL) cholesterol. This disease is usually caused by a mutation in genes such as LDL receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9. However, a considerable number of patients with hypercholesterolemia do not have any mutation in these candidate genes. In this study, we examined the difference in the metabolic level between patients with hypercholesterolemia and healthy subjects, and screened the potential biomarkers for this disease. METHODS: Analysis of plasma metabolomics in hypercholesterolemia patients and healthy controls was performed by gas chromatography-mass spectrometry and metabolic correlation networks were constructed using Gephi-0.9.2. RESULTS: First, metabolic profile analysis confirmed the distinct metabolic footprints between the patients and the healthy ones. The potential biomarkers screened by orthogonal partial least-squares discrimination analysis included l-lactic acid, cholesterol, phosphoric acid, d-glucose, urea, and d-allose (Variable importance in the projection > 1). Second, arginine and methionine metabolism were significantly perturbed in hypercholesterolemia patients. Finally, we identified that l-lactic acid, l-lysine, l-glutamine, and l-cysteine had high scores of centrality parameters in the metabolic correlation network. CONCLUSION: Plasma l-lactic acid could be used as a sensitive biomarker for hypercholesterolemia. In addition, arginine biosynthesis and cysteine and methionine metabolism were profoundly altered in patients with hypercholesterolemia.

17.
Am J Respir Cell Mol Biol ; 64(5): 617-628, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689672

RESUMO

Skeletal muscle dysfunction is one of the important comorbidities of chronic obstructive pulmonary disease (COPD); however, the underlying mechanisms remain largely unknown. RANKL (receptor activator of nuclear factor κB ligand), a key mediator in osteoclast differentiation, was also found to play a role in skeletal muscle pathogenesis. Whether RANKL is involved in COPD-related skeletal muscle dysfunction is as-of-yet unknown. We examined the expression of RANKL/RANK in skeletal muscles from mice exposed to cigarette smoke (CS) for 24 weeks. Grip strength and exercise capacity as well as muscular morphology were evaluated in CS-exposed mice with or without anti-RANKL treatment. The expressions of protein synthesis- or muscle growth-related molecules (IGF-1, myogenin, and myostatin), muscle-specific ubiquitin E3 ligases (MuRF1 and atrogin-1), and the NF-κb inflammatory pathway were also evaluated in skeletal muscles. The effect of CS extract on RANKL/RANK expression and that of exogenous RANKL on the ubiquitin-proteasome pathway in C2C12 myotubes were investigated in vitro. Long-term CS exposure induced skeletal muscle dysfunction and atrophy together with upregulation of RANKL/RANK expression in a well-established mouse model of COPD. RANKL neutralization prevented skeletal muscle dysfunction and atrophy. RANKL inhibition decreased expressions of myostatin and MuRF1/Atrogin1 and suppressed the NF-κb pathway in skeletal muscles from CS-exposed mice. In in vitro experiments with C2C12 myotubes, CS extract induced expression of RANKL/RANK, and exogenous RANKL induced activation of the ubiquitin-proteasome pathway and NF-κb pathway via RANK. Our results revealed an important role of the RANKL/RANK pathway in muscle atrophy induced by CS exposure, suggesting that RANKL may be a potential therapeutic target in COPD-related skeletal muscle dysfunction.

18.
J Mater Sci Mater Med ; 32(4): 36, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779853

RESUMO

To evaluate the performance of a composite scaffold of Wharton's jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young's modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

19.
Front Immunol ; 12: 627072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708218

RESUMO

The accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the development of MDSCs remain poorly understood. In this report, we showed that interferon regulatory factor 4 (IRF4) plays a key role in the development of PMN-MDSCs, but not monocytic MDSCs. IRF4 deficiency caused a significant elevation of PMN-MDSCs and enhanced the suppressive activity of PMN-MDSCs, increasing tumor growth and metastasis in mice. Mechanistic studies showed that c-Myc was up-regulated by the IRF4 protein. Over-expression of c-Myc almost abrogated the effects of IRF4 deletion on PMN-MDSCs development. Importantly, the IRF4 expression level was negatively correlated with the PMN-MDSCs frequency and tumor development but positively correlated with c-Myc expression in clinical cancer patients. In summary, this study demonstrated that IRF4 represents a novel regulator of PMN-MDSCs development in cancer, which may have predictive value for tumor progression.

20.
Dermatol Ther ; 34(2): e14844, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33528092

RESUMO

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double-blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3- and 6-month follow-ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3- and 6- month follow-ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = -.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.

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