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1.
Bioact Mater ; 19: 538-549, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35600977

RESUMO

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) derivatives as a carrier to conjugate a MR contrast agent, Gd-DOTA, and a two-photon fluorophore with an aggregation-induced emission (AIE) effect, TPBP, to construct a MR/two-photon fluorescence dual-modality contrast agent, Gd-DOTA-TPBP. Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r 1 value for Gd-DOTA-TPBP, revealing a great MR imaging resolution. The contrast agent specifically accumulated in the tumor region, allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging. Meanwhile, coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity, but also significantly enhanced its imaging performance in an aqueous phase. Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI. Since high-resolution, complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP, it has great potential in the early phase of disease diagnosis.

3.
Int Immunopharmacol ; 112: 109186, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36115280

RESUMO

OBJECTIVE: Exposure to PM2.5 will increase the risk of respiratory disease and increase the burden of social health care. Astragaloside Ⅳ (Ast-IV) is one of the main biologically active substances form Chinese herb Astragalus membranaceus, which owns various pharmacological effects. Ferroptosis is a novel form of cell death characterized by accumulation of iron-dependent lipid reactive oxygen species (ROS). It is not clear whether there are typical features of ferroptosis in PM2.5-induced lung injury. This study investigates whether PM2.5-induced lung injury in mice has a special form of ferroptosis and the specific protective mechanism of Ast-IV. SUBJECTS AND METHODS: Forty-two male C57BL/6J mice were randomly divided into six groups (n = 7 per group): NS group (normal saline), Ast group (Ast-IV 100 mg/kg), PM2.5 group, Ast-L group (Ast-IV 50 mg/kg + PM2.5), Ast-H group (Ast-IV 100 mg/kg + PM2.5) and Era group (Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5). Mice were pre-treated with Ast-IV intraperitoneally for three days. Then, PM2.5 (7.5 mg/kg) was given by non-invasive tracheal instillation to induce lung injury. The ferroptosis' agonist erastin was used to verify the mechanism of Ast-IV anti-ferroptosis. 12 h after PM2.5 stimulation, the mice were euthanized. Bronchoalveolar lavage fluid (BALF) and serum were collected for oxidative stress and cytokine determination. Lung tissues were collected for glutathione (GSH), tissue iron content, histology, immunofluorescence, transmission electron microscopy, and western blot analysis. RESULTS: Ast-IV reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury. CONCLUSION: The protective effect of Ast-IV on PM2.5-induced lung injury in mice might be related to the inhibition of ferroptosis in lung tissue. Anti-ferroptosis might be a new mechanism of Ast-IV on PM2.5-induced lung injury.

4.
Nature ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36049505

RESUMO

Perovskite solar cells (PSCs) with an inverted structure (often referred to as the p-i-n architecture) are attractive for future commercialization due to their easily scalable fabrication, reliable operation, and compatibility with a wide range of perovskite-based tandem device architectures1,2. However, the power conversion efficiency (PCE) of p-i-n PSCs falls behind n-i-p (or normal) structure counterparts3-6. This large performance gap could undermine efforts to adopt p-i-n architectures, despite their other advantages. Given the remarkable advances in perovskite bulk materials optimization over the past decade, interface engineering has become the most important strategy to push PSC performance to its limit7,8. Here, we report a reactive surface engineering approach based on a simple post-growth treatment of 3-(Aminomethyl)pyridine (3-APy) on top of a perovskite thin film. First, the 3-APy molecule selectively reacts with surface FA+, reducing perovskite surface roughness and surface potential fluctuations associated with surface steps/terraces. Second, the reaction product on the perovskite surface decreases the formation energy of charged iodine-vacancies, leading to effective n-type doping with a reduced work function in the surface region. With this reactive surface engineering, the resulting p-i-n PSCs obtained a PCE over 25%, along with retaining 87% of the initial PCE after over 2400 h of one-sun operation at about 55°C in air.

5.
J Infect Dis ; 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056912

RESUMO

Irrigated agriculture enhances food security, but it potentially promotes mosquito-borne disease transmission and affects vector intervention effectiveness. This study was conducted in the irrigated and non-irrigated areas of rural Homa Bay and Kisumu Counties, Kenya. We performed cross-sectional and longitudinal surveys to determine Plasmodium infection prevalence, clinical malaria incidence, molecular force of infection (molFOI), and multiplicity of infection. We examined the impact of irrigation on the effectiveness of the new interventions. We found that irrigation was associated with >2-fold higher Plasmodium infection prevalence and 3-fold higher clinical malaria incidence compared to the non-irrigated area. Residents in the irrigated area experienced persistent, low-density parasite infections and higher molFOI. Addition of indoor residual spraying was effective in reducing malaria burden, but the reduction was more pronounced in the non-irrigated area than in the irrigated area. Our findings collectively suggest that irrigation may sustain and enhance Plasmodium transmission and affects intervention effectiveness.

6.
Front Oncol ; 12: 959322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091173

RESUMO

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

8.
Clin Exp Nephrol ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083527

RESUMO

BACKGROUND: Hsa_circ_0080425 (circ_0080425) is newly identified to correlate with the progression of diabetic nephropathy (DN). However, its role and mechanism in DN process is not very clear. METHODS: Cell counting kit-8 assay, flow cytometry, scratch wound assay, and western blotting were performed to measure endothelial cell dysfunction. Expression of circ_0080425, microRNA (miR)-140-3p and fibronectin 1 (FN1) were determined by quantitative real-time PCR and western blotting. The direct interaction was confirmed by dual-luciferase reporter assay. RESULTS: High-glucose (HG) treatment could induce inhibition of cell proliferation, cell cycle entrance and wound healing rate in human umbilical vein endothelial cells (HRGEC), and enhancement of apoptosis rate. Circ_0080425 expression was upregulated by HG, and exhausting circ_0080425 could attenuate HG-induced above effects in HRGEC. MiR-140-3p was sponged by circ_0080425, and its inhibitor reversed the regulation of circ_0080425 knockdown on HG-induced HRGEC injury. FN1 was targeted by miR-140-3p, and its overexpression also restored the inhibitory effect of miR-140-3p on HC-induced HRGEC injury. CONCLUSION: Circ_0080425 expression might contribute to HG-induced endothelial cell injury, and circ_0080425/miR-140-3p/FN1 axis was a potential therapeutic approach to interfere DN process.

9.
Shanghai Kou Qiang Yi Xue ; 31(2): 132-137, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-36110068

RESUMO

PURPOSE: To investigate the expression change of microRNA (miR) - 199a in MC3T3-E1 cells stimulated by mechanical stretch and its mechanism of osteogenic differentiation. METHODS: MC3T3-E1 cells cultured in vitro were loaded with 12% stretch for 0, 3, 6, 12 and 24 hours, alkaline phosphatase (ALP) activity was detected by ALP activity test kit, the expressions of osteocalcin (OCN), osteoblast specific transcription factor osterix (OSX), Runt related transcription factor 2 (Runx2) mRNA and miR-199a were detected by real-time fluorescence quantitative PCR. MC3T3-E1 cells were divided into control group, stretch group, stretch + miR-NC group and stretch + miR-199a group, and the expressions of miR-199a, OCN, OSX, Runx2 mRNA and protein and ALP activity were observed after 12% stretch and transfection of miR-199a. Alizarin red S (ARS) staining was used to observe calcium nodule formation ability. The target relationship between miR-199a and insulin like growth factor-1 (IGF1) was detected by double luciferase reporter gene assay; in addition, the effect of miR-199a mimic on IGF1 mRNA and protein expression was detected by real-time fluorescent quantitative PCR and Western blot. SPSS 24.0 software package was used to analyze the data. RESULTS: Compared with those at the time point of 0 h, ALP activity and expression level of OCN, OSX and Runx2 mRNA of MC3T3-E1 cells at 3, 6, 12 and 24 hours after mechanical stretch stimulation were significantly higher, while the expression level of miR-199a was significantly lower(P<0.05), and the change was most significant at 12 h. Compared with those in the control group, the expression level of miR-199a was significantly lower in the stretch group, while ALP activity, the expression level of OCN, OSX and Runx2 mRNA and protein, calcium nodule formation level were significantly high in the stretch group(P<0.05); there was no significant difference in the above indexes between the stretch group and stretch + miR-NC group(P>0.05). Compared with stretch + miR-NC group, the expression level of miR-199a in stretch + miR-199a group was significantly higher; while ALP activity, OCN, OSX, Runx2 mRNA and protein expression level, calcium nodule formation level were significantly lower(P<0.05). miR-199a could targetedly bind to IGF1, and the expression level of IGF1 mRNA and protein in MC3T3-E1 cells was significantly reduced by miR-199a mimic(P<0.05). CONCLUSIONS: MiR-199a can inhibit the osteogenic differentiation of MC3T3-E1 cells induced by mechanical stretch stimulation, and its mechanism may be related to the targeted regulation of IGF1 expression.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , MicroRNAs , Fosfatase Alcalina/metabolismo , Cálcio/metabolismo , Cálcio/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteocalcina/farmacologia , Osteogênese/genética , RNA Mensageiro/metabolismo
10.
Mol Biol Rep ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129598

RESUMO

BACKGROUND: Long noncoding RNA ANRIL has been found to be involved in the pathogenesis of diabetic kidney disease (DKD) and is expected to be a new target for prevention of DKD. However, the circulating expression and clinical significance of ANRIL in DKD patients is uncertain. This study aims to explore this issue. METHODS: The study consisted of 20 healthy controls, 22 T2DM patients (normalbuminuria) and 66 DKD patients (grouped as follows: microalbuminuria, n = 23; macroalbuminuria, n = 22 and renal dysfunction, n = 21). The expressions of ANRIL in peripheral whole blood of all participants were measured by RT-qPCR. RESULTS: The expression of ANRIL was significantly up-regulated in DKD patients (microalbuminuria, macroalbuminuria and renal dysfunction groups) than that in healthy control group. ANRIL was also over-expressed in macroalbuminuria and renal dysfunction groups in comparison with normalbuminuria group. ANRIL expression was positively correlated with Scr, BUN, CysC, urine ß2-MG and urine α1-MG; while negatively correlated with eGFR in DKD patients. In addition, ANRIL was the risk factor for DKD with OR value of 1.681. The AUC of ANRIL in identifying DKD was 0.922, and the sensitivity and specificity of DKD diagnosis were 83.3% and 90.5%, respectively. CONCLUSION: Our results indicated that highly expressed ANRIL in peripheral blood is associated with progression of DKD. Circulating ANRIL is an independent risk factor of DKD and has a highly predictive value in identifying DKD.

11.
Front Immunol ; 13: 899971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911750

RESUMO

Immune checkpoint inhibitor-related pneumonitis (CIP) is a rare but well-recognized immune-related adverse event (irAE), causes 35% of irAE related deaths. However, the mechanism of CIP remains unclear and no evidence-based treatment except for glucocorticoids is available. Herein, we report the case of a patient with metastatic bladder cancer who received tislelizumab and was diagnosed with CIP. The patient underwent transbronchial cryobiopsy. The patient was treated with glucocorticoid, but CIP recurred when the glucocorticoid tapering. The paraffine-embedded lung tissue was sectioned, stained with 31 heavy-metal tagged antibodies, and analyzed using imaging mass cytometry (IMC) technology. We identified multiple immune cell subsets in the lung tissue and observed the infiltration of memory T cells and the CD4+ DC subset. The data indicated the great potential of IMC technology in the identification and characterization of irAEs. Further investigation is warranted to identify the mechanism of action of CIP.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Pneumonia , Antineoplásicos Imunológicos/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Citometria por Imagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/complicações , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico
12.
Front Surg ; 9: 907485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034368

RESUMO

The objective of this study was to investigate the platelet-to-lymphocyte ratio (PLR) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 197 patients who underwent intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder (TURB) were included. We divided the patients into different groups according to the treatment stage before and during induction treatment as Group 1 and Group 2, and set the change value of PLR as the Group 3. The cutoff values of PLR were determined through receiver operation characteristics curves analysis. we found a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between patients with high serum PLR and those with low serum PLR in Group 1, as well as Group 2. Cox multivariate analysis revealed that tumor number ≥3, high grade, and history of carcinoma in situ (CIS) were significant factors predicting RFS and PFS. The PLR values before and during induction therapy could be used as predictors for the progression and recurrence of NMIBC patients receiving BCG immunotherapy. the PLR values after induction therapy have a stronger predictive power.

13.
J Hepatol ; 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36038017

RESUMO

BACKGROUND & AIMS: Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. METHODS: In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. RESULTS: Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 µmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. CONCLUSIONS: Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. LAY SUMMARY: Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.

14.
Theranostics ; 12(13): 5824-5835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966575

RESUMO

Rationale: The transformation of fibroblasts into activated myofibroblasts is a critical step that results in cardiac fibrosis upon myocardial infarction (MI). Leucine-rich repeat-containing protein-8A (LRRC8A) is a multi-functional protein involved in cell survival, growth, and proliferation, whereas its role in regulating myofibroblast phenotypes and myocardial fibrosis remains unknown. Methods: Conditional myofibroblast-specific Lrrc8a knockout mouse models were established by crossing the Lrrc8a flox/flox mice with the tamoxifen-inducible periostin-Cre transgenic mice. The involvement of LRRC8A in regulating cardiac fibrosis post-MI and myofibroblast phenotypes induced by transforming growth factor-ß1 (TGF-ß1) was comprehensively evaluated. The mechanisms underlying LRRC8A regulation of myofibroblast phenotypes were determined by RNA sequencing-driven analysis followed by cause-effect experiments. Results: LRRC8A expression was significantly elevated in the fibrotic tissues and the fibroblasts isolated from the post-MI hearts. Compared with the wild-type (WT) littermates, the specific knockout of LRRC8A in myofibroblasts greatly attenuated myofibroblast transformation, fibrotic remodeling, and ventricular dysfunction after MI. Silencing of LRRC8A expression suppressed, whereas overexpression of LRRC8A enhanced, the pro-fibrotic myofibroblast phenotypes in isolated cardiac fibroblasts upon stimulation with TGF-ß1. LRRC8A participated in TGF-ß1-induced myofibroblast transformation via activating JAK2-STAT3 signaling. Furthermore, LRRC8A activated the JAK2-STAT3 pathway via its C-terminal leucine-rich repeat-domain (LRRD), directly interacting with growth factor receptor-bound protein 2 (GRB2), an adaptor protein associated with and necessary for tyrosine-phosphorylated JAK2. Conclusions: LRRC8A regulates myofibroblast transformation and cardiac fibrosis following MI. LRRC8A inhibition might be a promising strategy for cardiac fibrosis and heart failure.


Assuntos
Infarto do Miocárdio , Miofibroblastos , Animais , Proteínas de Transporte/metabolismo , Fibrose , Leucina/genética , Leucina/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Miofibroblastos/metabolismo , Fenótipo , Fator de Crescimento Transformador beta1/metabolismo
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121692, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35921752

RESUMO

Nitrite (NO2-) is an inorganic contaminant that exists widely in the environment including water and food products, excessive amounts of NO2- would threaten humans and aquatic life. Developing a rapid and convenient sensing method for NO2- remains a great challenge. Herein, a colorimetric and near-infrared fluorescent probe (TBM) was synthesized and applied for sensitively and selectively detecting NO2- in water, food samples and Escherichia coli (E. coli). With the addition of NO2-, the probe TBM solution has a distinct visual color changed from red to colorless and fluorescence intensity at 620 nm quickly decreased. The probe TBM could detect NO2- quantitatively with a detection limit of 85 nM based on a 3σ/slope. Under optimum conditions, TBM has been successfully used to detect NO2- in real-world environmental and dietary samples, with positive results. Besides, paper strips loaded with TBM have been used to visually determine NO2- levels. Most importantly, TBM has also been proven to be able to discriminate from different concentrations of NO2- in E. coli by fluorescence imaging. In summary, the probe TBM was successfully developed for the accurate quantification, naked eyes detection and bioimaging of NO2- in water, food samples and E. coli, which provides a useful tool to better guarantee the quality and safety of daily life and food industry.


Assuntos
Colorimetria , Corantes Fluorescentes , Colorimetria/métodos , Escherichia coli , Humanos , Nitritos , Dióxido de Nitrogênio , Água
16.
Nat Immunol ; 23(9): 1342-1354, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35995859

RESUMO

Appropriate regulation of B cell differentiation into plasma cells is essential for humoral immunity while preventing antibody-mediated autoimmunity; however, the underlying mechanisms, especially those with pathological consequences, remain unclear. Here, we found that the expression of Jmjd1c, a member of JmjC domain histone demethylase, in B cells but not in other immune cells, protected mice from rheumatoid arthritis (RA). In humans with RA, JMJD1C expression levels in B cells were negatively associated with plasma cell frequency and disease severity. Mechanistically, Jmjd1c demethylated STAT3, rather than histone substrate, to restrain plasma cell differentiation. STAT3 Lys140 hypermethylation caused by Jmjd1c deletion inhibited the interaction with phosphatase Ptpn6 and resulted in abnormally sustained STAT3 phosphorylation and activity, which in turn promoted plasma cell generation. Germinal center B cells devoid of Jmjd1c also acquired strikingly increased propensity to differentiate into plasma cells. STAT3 Lys140Arg point mutation completely abrogated the effect caused by Jmjd1c loss. Mice with Jmjd1c overexpression in B cells exhibited opposite phenotypes to Jmjd1c-deficient mice. Overall, our study revealed Jmjd1c as a critical regulator of plasma cell differentiation and RA and also highlighted the importance of demethylation modification for STAT3 in B cells.


Assuntos
Artrite Reumatoide , Histona Desmetilases com o Domínio Jumonji , Animais , Diferenciação Celular , Hematopoese , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Camundongos , Oxirredutases N-Desmetilantes/química , Oxirredutases N-Desmetilantes/genética , Oxirredutases N-Desmetilantes/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
17.
Orphanet J Rare Dis ; 17(1): 307, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927746

RESUMO

BACKGROUND AND AIMS: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse. METHODS: We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse. RESULT: Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse. CONCLUSION: Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.


Assuntos
Doença Relacionada a Imunoglobulina G4 , China , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/uso terapêutico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Recidiva , Estudos Retrospectivos
18.
Cancer Manag Res ; 14: 2323-2337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958946

RESUMO

Background: Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC. Methods: Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR. In vitro functional assays were used to evaluate the influences of tsRNAs on GC cells. The potential mechanisms underlying tsRNAs were explored using bioinformatics analysis,RT-qPCR, RNA immunoprecipitation assays and Western blot. Results: We found that tiRNA-Val-CAC-001 was downregulated in GC tissues and cells, and demonstrated that tiRNA-Val-CAC-001 was a tsRNA sheared from mature tRNA-Val and mainly localized in the cytoplasm. tiRNA-Val-CAC-001 overexpression inhibited metastasis and proliferation but promoted apoptosis of GC cells; nevertheless, tiRNA-Val-CAC-001 knockdown increased metastasis and proliferation and reduced apoptosis (P<0.05). GO and KEGG analyses indicated tiRNA-Val-CAC-001 may exert its effects via Wnt/ß-catenin signaling pathway by targeting LRP6. Following experiments showed that tiRNA-Val-CAC-001 could downregulated the protein levels of LRP6 and ß-catenin, but up-regulated p-ß-catenin, which confirmed the findings in bioinformatics analysis. Conclusion: In conclusion, tiRNA-Val-CAC-001 works as a cancer suppressor in GC by targeting LRP6 via Wnt/ß-catenin signaling pathway. tiRNA-Val-CAC-001 may serve as a therapy target and a biomarker of GC in the future. Key Points: tiRNA-Val-CAC-001 is downregulated in gastric cancer tissues and cell lines, tiRNA-Val-CAC-001 has potential to become a novel diagnostic biomarker in gastric cancer, and tiRNA-Val-CAC-001 regulates gastric cancer cells by targeting LRP6.

19.
Int Immunopharmacol ; 111: 109002, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932611

RESUMO

BACKGROUND: Thymosin beta 4 × (Tmsb4x) has been highlighted as an important regulator in immune and inflammation responses. Promoted differentiation of mononuclear cells into dendritic cells (DCs) exert a beneficial effect on septicemia. Herein, we investigated the effects of Tmsb4x on the mononuclear cells to affect immune responses during septicemia. METHODS: Initially, we isolated peripheral blood samples from healthy individuals and patients with septicemia for extraction of mononuclear cells, followed by Tmsb4x expression quantification. A cell model was constructed with mononuclear cells through lipopolysaccharide stimulation. The viability and apoptosis were evaluated in response to Tmsb4x silencing or re-expression. Additionally, the proportion of DCs was assessed by determining levels of inflammatory factors as well as by flow cytometric analysis. A mouse septicemia model was developed for in vivo validation. RESULTS: Cell and animal models demonstrated decreased Tmsb4x expression in the setting of septicemia, which led to increased inflammatory response and reduced proportion of DCs, along with inhibited mononuclear cell viability and promoted apoptosis. However, restoration of Tmsb4x facilitated the differentiation of mononuclear cells into DCs. CONCLUSION: To conclude, upregulated Tmsb4x promoted the generation of DCs from mononuclear cells, which contributed to deep understanding of underpinning mechanisms in the development of septicemia.


Assuntos
Sepse , Timosina , Animais , Diferenciação Celular , Células Dendríticas , Leucócitos Mononucleares/metabolismo , Camundongos , Timosina/metabolismo
20.
Bioresour Technol ; 362: 127855, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36037838

RESUMO

A hybrid activated sludge membrane-aerated biofilm reactor based on a two-stage simultaneous nitrification-denitrification (SND) process was built, and its utility for treating interflow with low chemical oxygen demand (COD)/total nitrogen (TN) (COD/N) was explored. The operating performance, functional microbial communities, and functional genes for nitrogen metabolism were evaluated at low COD/N (4-1.3). The reactor could achieve stable operation at COD/N = 4-1.5, and the removal efficiency of COD, TN, and ammonia nitrogen was stable at 90.30 ± 2.36 %, 85.69 ± 2.22 %, and 89.52 ± 6.06 %, respectively. The SND rates were 70.89 % and 50.75 % when influent COD/N was 2.0 and 1.7, respectively, indicating that SND makes an important contribution to nitrogen removal under these two COD/N conditions. Microbial analysis revealed that the sampling sites with a high abundance of denitrification genes in the outer ring experienced aerobic conditions, inferring that aerobic denitrification also plays an important role in denitrification.


Assuntos
Nitrogênio , Esgotos , Biofilmes , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Desnitrificação , Nitrificação , Nitrogênio/metabolismo , Eliminação de Resíduos Líquidos , Águas Residuárias
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