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N6-Methyladenosine (m6A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m6A-dependent. m6A "reader," Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) identified methylated PD-L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T-cell proliferation and its cancer cell-killing effects were prevented by overexpression of WTAP in vitro and in vivo. Overexpression prevented T cells from proliferating and killing CRC by maintaining the expression of PD-L1. Further evidence supporting the WTAP-PD-L1 regulatory axis was found in human CRC and organoid tissues. Tumors with high WTAP levels appeared more responsive to anti-PD1 immunotherapy, when analyzing samples from patients undergoing treatment. Overall, our findings demonstrated a novel PD-L1 regulatory mechanism by WTAP-induced mRNA epigenetic regulation and the possible application of targeting WTAP as immunotherapy for tumor hypoxia.
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Adenosina , Antígeno B7-H1 , Neoplasias Colorretais , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Animais , Camundongos , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Feminino , Hipóxia Tumoral/genética , Proteínas de Ciclo CelularRESUMO
Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.
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Heparina , Trombocitopenia , Animais , Camundongos , Heparina/farmacologia , Heparina/uso terapêutico , Anticoagulantes/farmacologia , Coagulação Sanguínea , Trombocitopenia/tratamento farmacológico , Contagem de PlaquetasRESUMO
BACKGROUND: Alterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA). METHODS: We conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis. RESULTS: PSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093-0.666, P = 0.006) in multivariate Cox regression analysis. CONCLUSION: WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.
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Gastroenteropatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Função da Barreira Intestinal , Estudos Retrospectivos , Flatulência , LactatosRESUMO
BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. OBJECTIVES: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. CONCLUSION: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.
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Janus Quinase 3 , Queloide , Humanos , Colágeno , População do Leste Asiático , Janus Quinase 1 , Janus Quinase 3/antagonistas & inibidores , Queloide/patologia , Pele/patologia , Resultado do TratamentoRESUMO
Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.
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Ataxia Cerebelar , Camundongos , Animais , Ataxia Cerebelar/induzido quimicamente , Células de Purkinje/fisiologia , Microglia , Fator de Necrose Tumoral alfa/farmacologia , Cerebelo , CitocinasRESUMO
Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Advanced stage CRC, during the recent past, had a dismal prognosis and only a few available treatments. Pumilio homologous protein 1 (PUM1) is reportedly aberrant in human malignancies, including CRC. However, the role of PUM1 in the regulation of tumor-initiating cells (T-ICs) remains unknown. Methods: The levels of messenger RNAs (mRNAs) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot analyses. Statistical analyses were performed to determine the associations between the levels of PUM1 and tumor features and patient outcomes. Whether PUM1 is a downstream target of miR-218-5p was verified by bioinformatics target gene prediction and qRT-PCR. Results: Herein, it was found that T-ICs, chemoresistance, and recurrent CRC samples all manifest increased PUM1 expression. Functional investigations have shown that PUM1 increased the self-renewal, tumorigenicity, malignant proliferation, and chemoresistance of colorectal cells. PUM1 activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway biochemically. Furthermore, it was discovered that miR-218-5p specifically targets T-ICs' PUM1 3'-untranslated region (3'-UTR). More importantly, the PUM1/PI3K/AKT axis regulates CRC cells' responses to treatment with cetuximab, and PUM1 overexpression increased cetuximab resistance. More evidence points to the possibility that low PUM1 may predict cetuximab benefits in CRC patients after analysis of the patient cohort, patient-derived tumor organoids, and patient-derived xenografts (PDXs). Conclusions: Taken together, the result of this work points to the critical function of the miR-218-5p/PUM1/PI3K/AKT regulatory circuit in regulating T-ICs characteristics and thus suggests possible therapeutic targets for CRC.
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Programmed cell death protein 1 (PD-1) checkpoint blockade therapy requires the CD28 co-stimulatory receptor for CD8+ T cell expansion and cytotoxicity. However, CD28 expression is frequently lost in exhausted T cells and during immune senescence, limiting the clinical benefits of PD-1 immunotherapy in individuals with cancer. Here, using a cereblon knockin mouse model that regains in vivo T cell response to lenalidomide, an immunomodulatory imide drug, we show that lenalidomide reinstates the anti-tumor activity of CD28-deficient CD8+ T cells after PD-1 blockade. Lenalidomide redirects the CRL4Crbn ubiquitin ligase to degrade Ikzf1 and Ikzf3 in T cells and unleashes paracrine interleukin-2 (IL-2) and intracellular Notch signaling, which collectively bypass the CD28 requirement for activation of intratumoral CD8+ T cells and inhibition of tumor growth by PD-1 blockade. Our results suggest that PD-1 immunotherapy can benefit from a lenalidomide combination when treating solid tumors infiltrated with abundant CD28- T cells.
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Antígenos CD28 , Receptor de Morte Celular Programada 1 , Animais , Linfócitos T CD8-Positivos , Fatores Imunológicos , Imunoterapia/métodos , Lenalidomida/farmacologia , CamundongosRESUMO
Nanhu Lake is a red tourist attraction in Jiaxing city and the birthplace of the "Red Boat Spirit."To identify the influence of environmental factors on the distribution of plankton communities after ecological restoration in different regions, the environmental factors and plankton community in areas A, B, C, D, and S of Nanhu Lake were investigated in January 2021 after the completion of the ecological restoration projects. The concentrations of total nitrogen(TN), dissolved total nitrogen (DTN), ammonia nitrogen (NH4+-N), nitrate nitrogen (NO3--N), total phosphorus (TP), and dissolved total phosphorus (DTP) in the ecological restoration areas were significantly lower, and the content of dissolved oxygen (DO) was significantly higher (P<0.05) than those in the non-restoration area. The main phytoplankton species in the study area belonged to Cyanophyta and Bacillariophyta, and the main zooplankton species were protozoans and rotifers. The phytoplankton biomass in the restored area was lower than that in the unrestored area, and the number of phytoplankton and zooplankton species increased. Clustering and principal coordinate analysis results showed significant differences in plankton communities among the restoration areas (P<0.05), and plankton structures in regions A and B were similar. Redundancy analysis (RDA) showed that the main environmental factors affecting the distribution of phytoplankton communities were DO, NO3--N, pH, and water temperature (WT). The main driving factors of zooplankton community distribution were DO, NO3--N, NH4+-N, and TP. The results clarified the phytoplankton community characteristics and environmental correlation in different regions of Nanhu Lake, which can provide data support and reference for water ecological restoration of the lake.
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Fitoplâncton , Zooplâncton , Animais , Lagos , Nitrogênio/análise , Fósforo/análise , Plâncton , Água/análiseRESUMO
Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.
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Queloide , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Queloide/metabolismo , Fator de Transcrição STAT3/metabolismo , Trombospondina 1/metabolismoRESUMO
The overwinter period is the pre-stage of the algal bloom, and the endogenous phosphorus (P) in sediments is one of the main P sources of algal blooms during this period. Based on the investigation of the water quality and sediment pollutants during the overwinter period of cyanobacteria (recruitment period and dormancy period), this study analyzed the P release characteristics of sediments in the horizontal and vertical directions and clarified the P release risk of sediments and the change in microbial community structures. The results showed that the lake bay was moderately eutrophic in the two periods of the study area, and the water quality and sediment nitrogen and P pollution were more serious, and the chlorophyll a content (Chl-a) was still at a high level in the overwinter period. The pseudo-second order model and the modified Langmuir model could respectively describe the P kinetics and sorption isotherm behavior in the sediment. The theoretical maximum P sorption capacities (Qmax) of sediments were bottom layer>middle layer>surface layer, and the highest value was 1.648 mg·g-1 with the highest P sorption rate constant of the pseudo second-order kinetic model of 6.292 g·(mg·min)-1. Additionally, the P adsorption parameters (Qmax, NAP, and EPC0) were mainly affected by the physical and chemical properties of the sediment itself and the nutritional level of the lake bay. The surface sediments from the dormancy period mainly played the role of P sinks, and the part of sediments from the recruitment period played the role of P sources, in which existed the risk of endogenous P release. The analysis of the microbial community structure in sediments indicated that the microbial diversity in the sediments during the dormancy period was higher than that during the recruitment period, and some microbial categories with phosphate-solubilizing function of relative abundance was high.
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Cianobactérias , Poluentes Químicos da Água , Adsorção , Baías , China , Clorofila A/análise , Monitoramento Ambiental , Eutrofização , Sedimentos Geológicos/química , Lagos/química , Fósforo/análise , Poluentes Químicos da Água/análiseRESUMO
OBJECTIVE: To investigate the correlation of the anterior lobe thickness of the prostate (ALTP) with bladder outlet obstruction (BOO), and evaluate the effect of ALTP on the clinical progression of BPH. METHODS: This retrospective study included 159 cases of BPH. We obtained the clinical indicators of the patients, including ALTP, prostate volume (PV), postvoid residual urine (PVR), maximum urinary flow rate (Qmax), BOO index (BOOI) and IPSS, and analyzed the correlations of ALTP with IPSS, PV, Qmax, age, PVR and BOOI. Using the ROC curve and cut-off point of ALTP, we compared the clinical indicators between the small and large ALTP groups, and analyzed the correlation between ALTP and the clinical progression of BPH. RESULTS: IPSS was not significantly correlated with ALTP (P > 0.05), nor was ALTP with PV and Qmax (P > 0.05). The area under the ROC curve was 0.742 (95% CI: 0.656ï¼0.828) and the cut-off point of ALTP was 0.65 cm. Statistically significant differences were observed in PV, Qmax, IPSS and the rate of surgery between the small ALTP (<0.65 cm) and large ALTP (≥0.65 cm) groups (P < 0.05). CONCLUSION: ALTP is not proportional to PV or to IPSS. ALTP ≥ 0.65 cm increases the incidence of BOO, and may be a risk factor for the clinical progression of BPH.
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Hiperplasia Prostática , Obstrução do Colo da Bexiga Urinária , Retenção Urinária , Masculino , Humanos , Hiperplasia Prostática/complicações , Próstata , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/etiologia , Progressão da DoençaRESUMO
Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism, by combining massive parallel sequencing of immune edited tumors and CRISPR library screens in syngeneic mouse tumor model and co-culture system. We find that the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Genetic inactivation of the machinery or re-introduction of ANKRD52 frequent patient mutations dampens the JAK-STAT-interferon-γ signaling and antigen presentation in cancer cells, largely by abolishing miR-155-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). Expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration in nearly all human cancer types. Our data indicate that the evolutionarily conserved miRNA pathway can be exploited by cancer cells to escape from T cell-mediated elimination and immunotherapy.
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Evasão da Resposta Imune , MicroRNAs/metabolismo , Neoplasias , Animais , Linhagem Celular Tumoral , Quimiocinas/metabolismo , Heterogeneidade Genética , Humanos , Imunoterapia , Interferon gama , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Neoplasias/genética , Fosfoproteínas Fosfatases , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Linfócitos TRESUMO
Constructing metal nanoparticle (MNP) composites from metal-organic framework (MOF) precursors has attracted extensive attention as the MOF precursors provide an excellent porous matrix for the generation of MNP composites, which enables the direct fabrication of well-dispersed MNP composites. In this work, a novel strategy is proposed to fabricate MNP composites by slow chemical reduction (SCR) of MOF precursors at room temperature. The reduction process is skillfully slowed via using ethanol as the solvent, and the formation of MNP composites is then realized by the SCR process. Briefly, BH4- slowly diffuses into an MOF precursor and in situ reduces metal ions to well-dispersed nanoscale MNP composites. Meanwhile, this SCR process breaks the coordination bonds from MOF precursors, leading to the generation of porous structures for the resulting composites. Interestingly, the composites inherit the morphology of MOF precursors well. Besides, this SCR strategy allows construction of MNP composites from different types of MOF precursors. The resulting Cu@HK-3 composites possess well-dispersed nanoscale Cu NPs and a porous architecture, which exhibit superior catalytic performance and stability in the Ullmann coupling reaction. This strategy provides a feasible, convenient, and energy-saving route to prepare MNP composites from MOF precursors with customizable morphology and well-dispersed MNPs.
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A covalent post-assembly strategy is developed to prepare a composite of dispersive MOF particles in an aerogel matrix. Briefly, the anhydride group-decorated MOF (UiO-66-NH2) particles covalently coupled with polyimide (PI) monomers through a one-pot amidation polymerization reaction, succeeding a process of gel-sol, freeze-drying and thermal-imidization to obtain the UiO-66-PI aerogel. The designed composite shows outstanding catalytic activity in CO2 cycloaddition and excellent adsorption capacity for dyes.
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BACKGROUND: Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage in this process remains uninvestigated. METHODS: We examined the therapeutic effects of ADSC and bone marrow-derived mesenchymal stem cells (BM-MSC) in the rat model of dialysis-induced peritoneal fibrosis using methylglyoxal. In addition, treatment of macrophages with the conditioned medium of ADSC and BM-MSC was performed individually to identify the beneficial component of the stem cell secretome. RESULTS: In the in vivo experiments, we found dialysis-induced rat peritoneal fibrosis was attenuated by both ADSC and BM-MSC. Interestingly, ADSC possessed a more prominent therapeutic effect than BM-MSC in ameliorating peritoneal membrane thickening while also upregulating epithelial cell markers in rat peritoneal tissues. The therapeutic effects of ADSC were positively associated with M2 macrophage polarization. In the in vitro experiments, we confirmed that interleukin-6 (IL-6) secreted by MSCs upon transforming growth factor-ß1 stimulation promotes M2 macrophage polarization. CONCLUSIONS: In dialysis-induced peritoneal fibrosis, MSCs are situated in an inflammatory environment of TGF-ß1 and secrete IL-6 to polarize macrophages into the M2 phenotype. Our findings reveal a previously unidentified role of tissue macrophage in this antifibrotic process. ADSC has the advantage of abundance and accessibility, making the application values extremely promising. In dialysis-induced peritoneal fibrosis, peritoneal mesothelial cells secrete transforming growth factor-ß1 (TGF-ß1) when exposed to methylglyoxal (MGO)-containing peritoneal dialysate. When situated in TGF-ß1, the inflammatory environment induces mesenchymal stem cells to secrete interleukin-6 (IL-6), IL-6 polarizes macrophages into the M2 phenotype. The dominant peritoneal tissue M2 macrophages, marked by upregulated Arg-1 expression, account for the attenuation of MGO-induced dedifferentiation of peritoneal mesothelial cells to maintain epithelial integrity.
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Células-Tronco Mesenquimais , Fibrose Peritoneal , Animais , Interleucina-6 , Macrófagos , Células-Tronco Mesenquimais/patologia , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/patologia , Fibrose Peritoneal/terapia , Ratos , Diálise RenalRESUMO
BACKGROUND: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer. MATERIALS AND METHODS: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel-Haenszel) or random-effects (DerSimonian-Laird) models were selected to summarise the collective effects. RESULTS: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. CONCLUSIONS: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.
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Predisposição Genética para Doença , Neoplasias/genética , Polimorfismo Genético , Receptores Purinérgicos P2X7/genética , HumanosRESUMO
Herein we described a novel repair approach for a left atrial esophageal fistula. Complete mediastinal debridement and simultaneous primary repairs of the left atrial posterior wall and the esophagus were completed under a median sternotomy, central cardiopulmonary bypass, left atrial circular incision around four pulmonary veins, inflamed left atrial posterior wall removal, and posterior pericardial opening.
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Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ablação por Cateter/efeitos adversos , Fístula Esofágica/cirurgia , Esôfago/cirurgia , Fístula Esofágica/diagnóstico , Fístula Esofágica/etiologia , Fístula/diagnóstico , Fístula/etiologia , Fístula/cirurgia , Átrios do Coração , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Cardiopatias/cirurgia , Humanos , Reoperação , Tomografia Computadorizada por Raios XRESUMO
PURPOSES: This study was designed to evaluate the effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma (GBC) after radical resection (R0). METHODS: A total of 267 GBC patients who underwent R0 resection from January 2004 to December 2014 were enrolled, including 54 patients with preoperative jaundice and 213 patients without jaundice. The clinicopathological parameters between the two groups were compared, and the correlation between preoperative jaundice and the long-term prognosis was furtherly analyzed. RESULTS: Unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT stage was an independent factor for prognosis. Furthermore, the intraoperative blood transfusion and pT stage were significant different between long-term survival (survive for more than 3 years) and those who died within 3 years (P < 0.05). CONCLUSION: Preoperative jaundice was not the independent factor resulting in the poor long-term prognosis of gallbladder carcinoma after R0 resection. The pT stage was the only long-term prognostic factor in all GBC patients regardless of preoperative jaundice.
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Neoplasias da Vesícula Biliar , Icterícia , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Icterícia/etiologia , Icterícia/patologia , Fígado/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Based on the historical monitoring survey data from 2018 to 2019, the temporal and spatial distribution characteristics and main influencing factors of nitrogen and phosphorus in the overlying water in Daihai Lake were analyzed, and the differences of the temporal and spatial distribution were discussed. The results showed that the content of total nitrogen and total phosphorus in the overlying water was at a high level, especially the total nitrogen content was obviously higher than that in other lakes in China. The content of total nitrogen ranged from 3.29 mg·L-1 to 4.99 mg·L-1, with a mean value of (3.93±0.33) mg·L-1; the content of total phosphorus ranged from 0.063 mg·L-1 to 0.163 mg·L-1, with a mean value of (0.111±0.023) mg·L-1. In spring and summer, the content of total nitrogen and total phosphorus in the overlying deep water from the middle of the lake was significantly higher than that in the surrounding area. In autumn, the contents decreased from east to west, and in winter, the contents in the shallow water of the southern area were higher than that in the northern area. Nitrogen and phosphorus in the overlying water were mainly in the dissolved state, and the proportions of total dissolved nitrogen and phosphorus were 86.62% and 77.84%, respectively. The dissolved nitrogen was dominated by nitrate, whereas dissolved phosphorus was dominated by organic phosphorus. The concentration of lake water and the release of endogenous nutrient salts are the main reasons for the high total nitrogen and phosphorus. To prevent further deterioration of water quality, it is suggested to carry out endogenous treatment and ecological restoration in combination with engineering measures.
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A novel perylene diimide (PDI) based acceptor P-PDI was synthesized by attaching a phenyl bridge to two octyloxy side chains. With two large volume side chains, the planarity of P-PDI was significantly reduced, leading to weak nano-aggregation of the PDI groups between the different acceptor molecules. Differential scanning calorimetry (DSC) experiments also revealed that P-PDI was amorphous, and demonstrating the aggregation of P-PDI was successfully suppressed. When blended with PTB7-Th to fabricate a polymer solar cell, a power conversation efficiency (PCE) of 2.21% was achieved, demonstrating that a conjugated bridge with a big volume side chain could significantly reduce the nano-scale aggregation of PDI based acceptor materials, which provides a new strategy to synthesize high efficiency acceptors based on PDI.