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Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.
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Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologiaRESUMO
Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.
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Cálcio , Nefrite Lúpica , Proteínas de Ligação a Fosfato , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/genética , Animais , Humanos , Camundongos , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/deficiência , Cálcio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Neutrófilos/metabolismo , Granulócitos/metabolismo , Células Mieloides/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Armadilhas Extracelulares/metabolismo , Diferenciação Celular , GasderminasRESUMO
Hypoxia has been reported to promote the proliferation and migration of thyroid cancer, while the special mechanism was still unclear. HIF-1α/carnitine palmitoyl-transferase 1A (CPT1A) was found to be associated with papillary thyroid carcinoma (PTC) but the biological role of CPT1A in PTC was not explored. The effects of hypoxia and carnitine palmitoyl-transferase 1A (CPT1A) expression on PTC cells were determined by cell counting kit-8 assay, detection of oxidative stress, inflammation response and mitochondrial membrane motential (MMP). Oil Red O staining and the detection of free fatty acids were performed to assess the status of lipid metabolism. Flow cytometric analysis was performed to assess cell apoptosis. Quantitative polymerase chain reaction (qPCR) and western blot analysis were applied to investigate the expressions of CPT1A and HIF-1α and the molecules involved cell function. The expressions of CPT1A and HIF-1α were significantly increased in PTC cells with or without hypoxia treatment. CPT1A overexpression or silencing promoted or inhibited cell viability, and hypoxia further repressed cell viability. In addition, CPT1A overexpression alleviates hypoxia-induced increased oxidative stress, inflammation response and elevated MMP. CPT1A overexpression enhanced palmitic acid-induced decreased cell growth, enhanced the metabolic capacity of free fatty acid and suppressed cell apoptosis. Animal experiments showed that CPT1A overexpression promoted PTC tumor growth, reduced lipid deposition, oxidative stress and inflammation, as well as enhancing cell function indicators. However, CPT1A silencing showed the opposite effects both in vitro and in vivo. Hypoxia induces the high expression of HIF-1α/CPT1A, thereby reprogramming the lipid metabolism of PTC cells for adapting the hypoxia environment, meanwhile inhibiting the cell damage and apoptosis caused by oxidative stress.
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Metabolismo dos Lipídeos , Neoplasias da Glândula Tireoide , Animais , Câncer Papilífero da Tireoide/genética , Estresse Oxidativo , Neoplasias da Glândula Tireoide/genética , Hipóxia , Inflamação , Ácidos Graxos , CarnitinaRESUMO
This cohort study evaluated the associations of different treatments with the prognosis of follicular variant papillary thyroid carcinoma (FVPTC) and classical papillary thyroid carcinoma (CPTC) patients. The data of 69034 PTC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year mortality of CPTC and FVPTC patients receiving surgery, radiation and combination therapy were compared. The univariable and multivariable cox proportional risk models explored the associations between different treatments and the 5-year mortality in CPTC and FVPTC patients. The 5-year mortality of CPTC patients was 2.81% and FVPTC patients was 2.47%. Compared with CPTC receiving lobectomy and/or isthmectomy, those not receiving surgery were associated with increased risk of 5-year mortality [Hazards ratio (HR)=3.27, 95% confidence interval (CI): 2.55-4.20] while total thyroidectomy was correlated with reduced risk of 5-year mortality (HR=0.67, 95%CI: 0.55-0.80). Radioactive iodine (RAI) was linked with decreased risk of 5-year mortality in CPTC patients (HR=0.57, 95%CI: 0.50-0.65). CPTC patients undergoing both surgery and radiation were related to decreased risk of 5-year mortality compared with those receiving surgery only (HR=0.55, 95%CI: 0.48-0.63). CPTC patients receiving neither surgery nor radiation (HR=4.53, 95%CI: 3.72-5.51) or those receiving radiation (HR=1.98, 95%CI: 1.13-3.48) were correlated with elevated risk of 5-year mortality. The elevated risk of 5-year mortality in FVPTC patients was reduced in those undergoing RAI (HR=0.63, 95%CI: 0.51-0.76). In conclusion, combination therapy was associated with decreased risk of 5-year mortality in CPTC and FVPTC patients, which might provide a reference for the management of these patients.
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Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Câncer Papilífero da Tireoide/cirurgia , Estudos de Coortes , Radioisótopos do Iodo/uso terapêutico , Prognóstico , Estudos RetrospectivosRESUMO
Osteosarcoma is a bone cancer formed by the cells of the bone. Children, young adults, and teens are highly affected by osteosarcoma. Early identification of osteosarcoma is mandatory to improve the treatment and increase the lifespan of the patients. MicroRNA-195 (miR-195) was shown to be a suitable biomarker for osteosarcoma, and the present study describes a sensitive method of miR-195 identification by nuclease digestion in ELISA to detect and quantify the level of miR-195. S1 nuclease catalyzed endo- and exonucleolytic digestion of single-stranded (ss) RNA and DNA on ELISA polystyrene substrate, which helped to identify duplexed miR-195. This method selectively and specifically identified miR-195 without any biofouling interactions and reached the limit of detection at 10 fM within the range from 10 fM to 10 nM. Due to complete digestion of ssDNA, single- and triple-mismatched sequences failed to increase the ELISA signal, indicating specific miRNA detection. Furthermore, human serum spiked with miR-195 did not interfere with the detection, confirming selective identification. This method identified miR-195 at a lower level and will help to diagnose earlier stages of osteosarcoma.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Adolescente , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Criança , Digestão , Ensaio de Imunoadsorção Enzimática , Humanos , MicroRNAs/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/terapia , Adulto JovemRESUMO
SHP2 is a protein tyrosine phosphatase (PTP) that can regulate the tyrosine phosphorylation level. Overexpression of SHP2 will promote the development of cancer diseases, so SHP2 has become one of the popular targets for the treatment of cancer. Studies have reported that both SHP099 and SHP844 are inhibitors of SHP2 and bind to different allosteric sites 1 and 2, respectively. Studies have shown that combining SHP099 with SHP844 will enhance pharmacological pathway inhibition in cells. This study uses molecular dynamic simulations to explore the dual allosteric targeted inhibition mechanism. The result shows that the residues THR108-TRP112 (allosteric site 1) move to LEU236-GLN245 (αB-αC link loop in PTP domain) , the residues of GLN79-GLN87 (allosteric site 2) get close to LEU262-GLN269 (αA-αB link loop in PTP domain) and HIS458-ARG465 (P-loop) come near to ARG501-THR507 (Q-loop) in SHP2-SHP099-SHP844 system, which makes the "inactive conformation" more stable and prevents the substrate from entering the catalytic site. Meanwhile, residue GLU110 (allosteric site 1), ARG265 (allosteric site 2), and ARG501 (Q-loop) are speculated to be the key residues that causing the SHP2 protein in auto-inhibition conformation. It is hoped that this study will provide clues for the development of the dual allosteric targeted inhibition of SHP2.
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Neoplasias , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Regulação Alostérica , Sítio Alostérico , Humanos , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismoRESUMO
RESEARCH QUESTION: Does the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified-warmed embryo transfer in women with adenomyosis undergoing IVF? DESIGN: This retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified-warmed embryo transfer. RESULTS: Statistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, Pâ¯=â¯0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted ORâ¯=â¯1.628, 95% confidence interval 1.011-2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, Pâ¯=â¯0.005) and clinical pregnancy rates (44% versus 33.5%, P = 0.045) between the LNG-IUS group and control group. CONCLUSIONS: The results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials.
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Adenomiose/terapia , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Infertilidade Feminina/terapia , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Adenomiose/complicações , Adenomiose/tratamento farmacológico , Adenomiose/epidemiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Transferência Embrionária/estatística & dados numéricos , Embrião de Mamíferos , Feminino , Fertilização in vitro/estatística & dados numéricos , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/epidemiologia , Levanogestrel/farmacologia , Cuidado Pré-Concepcional/métodos , Gravidez , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , VitrificaçãoRESUMO
PURPOSE: To define if exposure to tobacco smoke (TS) could induce reduction of bone mass and impairment of bone architecture, features observed in osteoporosis in normotensive rats and the influence of TS exposure on the osteoporotic features exhibited in the spontaneously hypertensive (SH) rats. METHODS: Normotensive Wistar Kyoto (WKY) and SH rats were exposed to filtered air or TS for 8 weeks, then their proximal femurs were extracted for micro-computed tomography (micro-CT) assessment, histological and immune-histological examinations to quantify the adverse influence of TS exposure on the bone mass and density, as well as bone architecture. RESULTS: We found that TS exposure not only induced significant decreases in bone mineral density (BMD), bone volume (BV), cortical and trabecular thickness (Ct.Th and Tb.Th), trabecular surface area (Tb.Ar), expression of hypoxia-inducible factor-1α (HIF-1α) in the trabecular marrow, delayed ossification of cartilage, as well as statistical increases in trabecular separation (Tb.SP) and the number of trabecular marrow adipocytes in both WKY and SH rats, but also exacerbated multiple features of osteoporosis exhibited in SH rats, including decreased BMD, Ct.Th, Tb.Ar, HIF-1α expression, delayed cartilage ossification, and increased Tb.SP. CONCLUSIONS: Our results show that TS exposure can reduce bone mass and impair bone architecture and exacerbate multiple features of osteoporosis exhibited in SH rats.
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Densidade Óssea/efeitos dos fármacos , Colo do Fêmur/efeitos dos fármacos , Nicotiana , Osteoporose/metabolismo , Fumaça/efeitos adversos , Animais , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiologia , Hipertensão/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Osteoporose/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fator A de Crescimento do Endotélio Vascular/metabolismo , Microtomografia por Raio-XRESUMO
AIMS: Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). METHODS: Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. RESULTS: In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 µM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. CONCLUSIONS: Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO.
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Citocinas/metabolismo , Pressão Hidrostática , Miócitos de Músculo Liso/metabolismo , Receptores Muscarínicos/metabolismo , Obstrução do Colo da Bexiga Urinária/metabolismo , Acetilcolina/farmacologia , Animais , Doença , Feminino , Humanos , Antagonistas Muscarínicos/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND: The discussion on the role of mechanical bowel preparation and oral antibiotics in elective colorectal surgery is still ongoing. OBJECTIVE: This meta-analysis aimed to determine whether oral systemic antibiotics with mechanical bowel preparation are superior to systemic antibiotics and mechanical bowel preparation for prophylaxis of bacterial infection during elective colorectal operation. DATA SOURCES: Embase, PubMed, and the Cochrane Library were searched using the terms oral, antibiotics/antimicrobial, colorectal/rectal/colon/rectum, and surgery/operation. STUDY SELECTION: All of the available randomized controlled trials that compared the efficacy of combined oral and systemic antibiotics and mechanical bowel preparation with systemic antibiotics alone and mechanical bowel preparation in colorectal surgery and defined surgical site infection based on Centers for Disease Control and Prevention criteria were included. INTERVENTION: All of the statistical analyses were performed using Review Manager 5.2 software. A fixed model was used if there was no evidence of heterogeneity; otherwise, a random-effects model was used. MAIN OUTCOME MEASURES: We focused on incidence of surgical site infection among the groups. RESULTS: Seven randomized controlled trials that consisted of 1769 cases were eligible for analysis. We found that both total surgical site infection and incisional surgical site infection were significantly reduced in patients who received oral systemic antibiotics and mechanical bowel preparation compared with patients who received systemic antibiotics alone and mechanical bowel preparation (total: 7.2% vs 16.0%, p < 0.00001; incisional: 4.6% vs 12.1%, p < 0.00001). However, no significant difference was detected in the rate of organ/space surgical site infection (4.0% vs 4.8%; p = 0.56) after elective colorectal surgery. LIMITATIONS: The meta-analysis was limited by the risk of bias because a majority of the studies did not use the blinding method. CONCLUSIONS: Oral systemic antibiotics and mechanical bowel preparation significantly lowered the incidence of surgical site infection after elective colorectal surgery compared with systemic antibiotics alone and mechanical bowel preparation.
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Bladder cancer is the most common malignancy of the urinary tract and in many patients is metastatic at diagnosis. Chemotherapy is the standard treatment for these patients but has serious side effects and in many patients is not tolerated. To avoid the side effects of systemic chemotherapy, patients with late stage bladder cancer have sought cryotherapy in our hospital. We reviewed data for the past 4 years to evaluate the safety and efficiency of percutaneous cryotherapy in 23 patients. Within 3 days after cryosurgery, all complications of bladder cancer (e.g. hematuria, urinary irritation, hypogastralgia, lumbago) had decreased to some degree. No new complications (e.g. bladder perforation) occurred and all complications had disappeared completely after 2 weeks. The progression-free survival (PFS) of these patients was 14 ± 8 months. There was no effect on PFS of tumor location or histopathology; however, differentiation status and tumor size influenced the therapeutic effect of percutaneous cryoablation. In conclusion, percutaneous cryotherapy may be a safe and efficacious therapeutic option in the treatment of metastatic bladder cancer.
Assuntos
Neoplasias Abdominais/terapia , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/terapia , Crioterapia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/secundário , Neoplasias Abdominais/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Criocirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Endophytic fungi play an important role in terrestrial ecosystem, while little is known about those in hemi-parasitic plants, a group of special plants which absorb nutrients from its hosts by haustoria. The relationship of the endophytes in the two parts of the bipartite systems (hemiparasites together with their hosts) is also poorly understood. Endophytic fungi of a hemi-parasitic plant Macrosolen tricolor, and its host plant Camellia oleifera were investigated and compared in this study. M. tricolor contained rich and diversified endophytic fungi (H' = 2.829), which consisted mainly of ascomycetes, distributed in more than ten orders of four classes (Sordariomycetes, Dothideomycetes, Leotiomycetes and Eurotiomycetes) besides Incertae sedis strains (23.2 % of total). In addition, 2.2 % of isolates were identified to be Basidiomycota, all of which belonged to Agaricomycetes. Obvious differences were observed between the endophytic fungal assembles in the leaves and those in the branches of M. tricolor. The endophytic fungi isolated from C. oleifera distributed in nearly same orders of the four classes of Ascomycota and one class (Agaricomycetes) of Basidiomycota as those from M. tricolor with similar proportion. For both M. tricolor and C. oleifera, Valsa sp. was the dominant endophyte species in the leaves, Torula sp. 1 and Fusarium sp. 1 were the dominant endophytic fungi in the branches. The similarity coefficient of the endophyte assembles in the two host was 64.4 %. Canonical correspondence analysis showed that the endophyte assembles of M. tricolor and C. oleifera were significantly different (p < 0.01).
Assuntos
Camellia/microbiologia , Endófitos/isolamento & purificação , Fungos/isolamento & purificação , Loranthaceae/microbiologia , Plantas Daninhas/microbiologia , Biodiversidade , Camellia/fisiologia , Endófitos/classificação , Endófitos/genética , Fungos/classificação , Fungos/genética , Loranthaceae/fisiologia , Dados de Sequência Molecular , Plantas Daninhas/fisiologiaRESUMO
Aim: We hypothesized plasma sEH activity correlates with mortality in acute respiratory distress syndrome (ARDS) patients. Methods: Adult patients diagnosed with ARDS enrolled between 2017 and 2019 were included in this study. Results: A total of 337 adult patients met our inclusion criteria. Among them, 107 patients died within 28 days. The plasma sEH activity was higher in nonsurvivors relative to survivors. And a receiver operating characteristic curve with the area under the curve of 0.81 (95% confidence interval: 0.74-0.89) for the prediction of 28-day mortality was obtained. Its sensitivity and specificity were 72.5% and 74.6%, respectively. Conclusion: Elevated plasma sEH activity is associated with higher 28-day mortality in adult patients with ARDS.
[Box: see text].
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Background: The increasing utilization of endoscopic lumbar discectomy (ELD) in spinal surgery has sparked widespread interest and research. This study utilizes bibliometric analysis to identify current research trends and advancements in this innovative surgical technique, with the goal of informing and improving surgical practices. Methods: We retrieved relevant literature on ELD from the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as research samples. Various visualization tools, such as VOSviewer, CiteSpace, Scimago Graphica, Pajek, and online bibliometric platform, were employed to generate scientific knowledge maps for the purpose of visual presentation and data analysis. Results: Over the past two decades, there has been significant progress in the research related to ELD, particularly since 2016. China has emerged as the most productive country, while South Korea and the United States have exerted greater academic influence. Tongji University has contributed the highest number of research output, while academic achievements published by Wooridul Spine Hospital are highly esteemed by scholars. Lee SH and Ruetten S are the most prolific author and the most highly cited author, respectively. World Neurosurg has published the highest number of publications, while Spine has become the most influential journal. Clinical Neurology and Surgery are the primary subject categories. Research in this field primarily revolves around improving ELD techniques, evaluating postoperative efficacy and prognosis prediction, studying complications and risk factors, as well as comparative research with other surgical techniques. Keywords such as risk factors, LDH, PETD, lumbar spinal stenosis, degeneration, recurrent herniation, laminectomy, local anesthesia, and foraminoplasty highlight the current research hotspots and future cutting-edge trends. Conclusion: This study employed bibliometric analysis to elucidate the research hotspots and frontiers in ELD. The findings have significant implications for advancing research and development in this field.
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BACKGROUND: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. OBJECTIVE: The study aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. METHODS: Differential expression analysis was conducted on disulfide-related genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116 dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. RESULTS: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally high expression of RPN1 in the femur of ovariectomized rats. CONCLUSION: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.
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Quempferóis , Simulação de Acoplamento Molecular , Osteoporose , Quempferóis/farmacologia , Quempferóis/química , Animais , Osteoporose/tratamento farmacológico , Ratos , Humanos , Feminino , Ratos Sprague-Dawley , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Endorribonucleases/metabolismoRESUMO
Integrin αvß6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by concerns over inflammatory-related side effects. The role of αvß6 in renal inflammation remains unknown, and clarifying this issue is crucial for αvß6-targeted treatment of chronic kidney disease (CKD). Here, we revealed a remarkable positive correlation between overexpressed αvß6 in proximal tubule cells (PTCs) and renal inflammation in CKD patients and mouse models. Notably, knockout of αvß6 not only significantly alleviated renal fibrosis but also reduced inflammatory responses in mice, especially the infiltration of pro-inflammatory macrophages. Furthermore, conditional knockout of αvß6 in PTCs in vivo and co-culture of PTCs with macrophages in vitro showed that depleting αvß6 in PTCs suppressed the migration and pro-inflammatory differentiation of macrophages. Screening of macrophage activators showed that αvß6 in PTCs activates macrophages via secreting IL-34. IL-34 produced by PTCs was significantly diminished by αvß6 silencing, and reintroduction of IL-34 restored macrophage activities, while anti-IL-34 antibody restrained macrophage activities enhanced by αvß6 overexpression. Moreover, RNA-sequencing of PTCs and verification experiments demonstrated that silencing αvß6 in PTCs blocked hypoxia-stimulated IL-34 upregulation and secretion by inhibiting YAP expression, dephosphorylation, and nuclear translocation, which resulted in the activation of Hippo signaling. While application of a YAP agonist effectively recurred IL-34 production by PTCs, enhancing the subsequent macrophage migration and activation. Besides, reduced IL-34 expression and YAP activation were also observed in global or PTCs-specific αvß6-deficient injured kidneys. Collectively, our research elucidates the pro-inflammatory function and YAP/IL-34/macrophage axis-mediated mechanism of αvß6 in renal inflammation, providing a solid rationale for the use of αvß6 inhibition to treat kidney inflammation and fibrosis.
Assuntos
Integrinas , Macrófagos , Camundongos Knockout , Insuficiência Renal Crônica , Animais , Macrófagos/metabolismo , Camundongos , Humanos , Integrinas/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Masculino , Antígenos de Neoplasias/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Modelos Animais de Doenças , Proteínas de Sinalização YAP/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , FibroseRESUMO
Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.
Assuntos
Diterpenos , Nefropatias , Proteína cdc42 de Ligação ao GTP , Animais , Camundongos , beta Catenina/efeitos dos fármacos , beta Catenina/metabolismo , Fibrose/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Rim/metabolismo , Nefropatias/tratamento farmacológico , Wikstroemia/química , Diterpenos/farmacologia , Proteína cdc42 de Ligação ao GTP/efeitos dos fármacosRESUMO
Saccharina japonica is one of the most important economic seaweeds. Several aspects such as photosynthesis in Saccharina lives are affected by blue light, the predominant light spectrum in the habitat. In this study, transcriptome profiling of S. japonica by next generation sequencing technology generated 55,102 qualified transcripts and 40.5 % transcripts were assigned to functional annotation. Expression of a large proportion of genes has been previously reported to be regulated by blue light, taking dark as control. However, by comparison among white, blue and red light, the significantly differentially expressed gene tags (DEGs) accounted for only 6.75 % of the identified sequences. It indicated that light-regulated gene expression in kelps is not a specific blue-light response. Unexpectedly, red light had more extensive effects on the transcriptomic activity than blue light did, since the most (68.4 %) DEGs were red light-regulated and only 17.5 % were specifically regulated by blue light. Some of the DEGs with the highest mRNA levels under blue light are not blue light-upregulated but red light-downregulated. The extensive regulation on gene expression under red light together with the abundant presence of phytochrome-like protein gene tags in S. japonica indicated their significant roles in the lives of brown algae. By highlighting the photosynthetic metabolism, blue light is more efficient than red light in triggering the pigment biosynthesis, light reaction and carbon fixation, revealing a molecular basis for rapid growth of kelps, since most of the time blue light is predominant in their habitat.
Assuntos
Phaeophyceae/metabolismo , Phaeophyceae/efeitos da radiação , Transcriptoma , Cor , Perfilação da Expressão GênicaRESUMO
Most patients with central type lung cancer (CTLC) are not candidates for surgery; systemic chemotherapy and external beam radiotherapy are the main treatments but have not greatly affected patient outcome. Combined percutaneous and endobronchial cryotherapy has been used successfully to treat CTLC; this study aimed to determine its feasibility and safety. Forty-seven patients with unresectable CTLC (22 endotracheal, 26 tracheal wall and 21 extratracheal tumors) underwent 69 sessions of combined percutaneous cryosurgery, endobronchial cryosurgery and airway stenting. The long diameter of all tumors was <5 cm. Biopsy showed non-small cell lung cancer (NSCLC) in 40 patients (medium or well differentiated in 20 cases, poorly differentiated in 20) and small cell lung cancer (SCLC) in seven. Within 3 days after treatment, ventilatory capacity and performance status had obviously increased and cough, signs of dyspnea, hemoptysis and atelectasis improved significantly, but symptoms of pneumothorax and pleural effusion emerged. After 2 weeks, all complications had disappeared completely, as had cough. Progression-free survival (PFS) for endotracheal tumors (8 ± 4 months) was shorter than that for tracheal wall (13 ± 6 months, P < 0.05) and extratracheal (14 ± 8 months, P < 0.01) tumors. The PFS of NSCLC (11 ± 5 months) was significantly longer than that of SCLC (4 ± 2 months, P < 0.0001). The PFS of medium or well differentiated CTLC (15 ± 8 months) was significantly longer than that of poorly differentiated CTLC (7 ± 3 months, P < 0.0001). In conclusion, combined cryotherapy is a safe and effective treatment for CTLC, with PFS largely influenced by tumor location and pathologic type.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Criocirurgia/métodos , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Carcinoma de Pequenas Células do Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do TratamentoRESUMO
Background and Objective: Apoptosis-inducing factor (AIF), a flavin protein in mitochondria, is originally found to induce apoptosis under the stimulation of pro-apoptotic factors. As a mitochondrial flavin adenine dinucleotide-dependent oxidoreductase, AIF is involved in the regulation of mammalian cell metabolism by regulating respiratory enzyme activity, antioxidant stress, promoting mitochondrial autophagy and glucose uptake, etc. Herein, we focused on the research progress regarding the molecular mechanism of AIF in metabolic mediation and the recent research on AIF in metabolic diseases, as well as the AIF-mediated apoptotic process. Methods: Articles for this paper were obtained by reviewing the literature related to the role of AIF in metabolic diseases on PubMed. The search terms included the following: "apoptosis", "metabolism" or "metabolic diseases" plus "apoptosis-inducing factor". The titles, abstracts, and full texts of relevant English-language publications published from October 1996 to June 2022 were manually screened to clarify the role of AIF in metabolic diseases. Key Content and Findings: We found that AIF played an important role in a variety of metabolically-related diseases, such as diabetes, obesity, metabolic syndrome, and tumor metabolism, by mediating apoptosis. Conclusions: We summarized the important role of AIF in a variety of metabolic diseases, which might help to further expand the understanding of AIF and to develop AIF-related therapeutic targets.