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1.
Nanoscale ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809512

RESUMO

This research addresses the fatigue behavior of freestanding nickel-molybdenum-tungsten (Ni-Mo-W) thin films with high-density planar faults. The as-deposited Ni-Mo-W thin films demonstrate an unprecedented fatigue life, withstanding over a million cycles at a Goodman stress amplitude (Sa,Goodman) of 2190 MPa - nearly 80% of the tensile strength. The texture, columnar grain width, planar fault configuration (spacing and orientation), and tensile strength were unchanged after annealing at 500 °C for 24 hours, and the film endured over 2 × 105 cycles at Sa,Goodman of 1050 MPa. The fatigue life of annealed Ni-Mo-W thin films is comparable to those of nanocrystalline Ni-based alloys, but has deteriorated significantly compared to that of the as-deposited films. The high fatigue strength of Ni-Mo-W thin films is ascribed to extremely dense planar faults suppressing fatigue crack initiation, and planar fault-dislocation interaction and grain boundary plasticity are proposed as mechanisms responsible for the fatigue failure. Provisionally the latter is a more convincing account of the experimental results, in which changes in the grain boundary characteristics after annealing cause higher susceptibility to stress concentration during cyclic loading. The fatigue behavior revealed in this work consolidates the thermal and mechanical reliability of Ni-Mo-W thin films for potential nano-structural applications.

2.
ACS Nano ; 18(13): 9713-9735, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507590

RESUMO

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Matriz Extracelular/metabolismo , Imunoterapia , Fibrose , Microambiente Tumoral
3.
Clin Transl Med ; 14(2): e1564, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38344897

RESUMO

Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.


Assuntos
Endometriose , Infertilidade , Feminino , Humanos , Animais , Camundongos , Endometriose/genética , Endometriose/metabolismo , Histonas/genética , Histonas/metabolismo , RNA/metabolismo , Fatores de Transcrição/metabolismo , RNA Mensageiro/metabolismo , Metilação , Hipóxia/complicações , Hipóxia/genética
4.
Clin Oral Investig ; 27(11): 6597-6606, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37736812

RESUMO

OBJECTIVE: To determine factors influencing survival and prognosis of HPV-related and non-related oropharyngeal cancer. METHODS: Subjects were determined from the three hospitals in Anhui province of China between 2015 and 2020. Paraffin-embedded specimens from participants' tissues were analyzed, and the subjects were classified as P16 + and P16 - cases using immunohistochemical staining for P16 protein. RESULTS: A total of 426 patients with oropharyngeal cancer were recruited in this study; 108 cases were found to be P16 + . The subjects were treated with the three regimens: surgery/radiotherapy/chemotherapy (SRCT), radiotherapy/chemotherapy (RCT), and surgery/chemotherapy (SCT). There were no statistically significant differences in the survival rates within the P16 + or P16 - groups between the three treatment regimens (P > 0.05). The 1-, 3-, and 5-year survival rates for P16 + and P16 - groups were statistically different (P < 0.05). Multivariate analysis showed that age, physical health status, smoking, and alcohol abuse were independent risk factors affecting the prognosis of P16 + cases, while pathological grading and TNM staging were independent risk factors affecting the P16 - cases. CONCLUSION: The etiology, pathogenesis, survival status, and prognostic factors of HPV-related oropharyngeal cancer are very different from those of traditional oropharyngeal cancer. Thus, HPV-related oropharyngeal cancer could be classified as a separate type of disease. This distinction could be of great significance for treatment, prevention, and prognostication of oropharyngeal cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Prognóstico , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia
6.
Cell Tissue Bank ; 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501011

RESUMO

Knee osteoarthritis (KOA) is a chronic joint disease characterized by the degeneration of articular cartilage. In this study, we explored the potential therapeutic effects of platelet-rich plasma (PRP) and identified molecular targets for treating KOA. A rat model of KOA was established via the Hulth method and primary knee joint chondrocytes were isolated to evaluate the effects of PRP and shRNA targeting p65 (sh-p65). ELISA was used to detect inflammatory factors, including IL-6, IL-1ß, and TNF-α. HE staining, Safranin O/Fast Green staining and Masson staining were performed to evaluate the morphology of articular cartilage, followed by detection of p65, COL2A1, ACAN, MMP13, and ADAMTS5 expression. The proliferation and apoptosis of primary knee chondrocytes were detected by the CCK-8 assay and TUNEL staining, respectively. Treatment with either PRP or sh-p65 decreased IL-6, IL-1ß, and TNF-α levels in the peripheral blood of KOA rats and chondrocyte culture supernatants, increased COL2A1 and ACAN levels, and decreased MMP13 and ADAMTS5 expression. Furthermore, administration of PRP or sh-p65 exerted protective effects on articular cartilage, enhanced the vitality of knee joint chondrocytes, and inhibited apoptosis. Collectively, PRP inhibited inflammation, promoted chondrocyte proliferation and cartilage matrix secretion, and induced cartilage regeneration by suppressing p65 expression; these effects allow PRP to alleviate KOA progression. P65-based targeted therapy administered in combination with PRP might be a promising strategy for treating KOA.

7.
J Pathol ; 260(3): 248-260, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36992523

RESUMO

Endometriosis is a common gynecological disorder that causes female infertility. Our recent research found that excessive oxidative stress in ovaries of endometriosis patients induced senescence of cumulus granulosa cells. Here, we analyzed the transcriptomic and metabolomics profiles of follicles in a mouse model of endometriosis and in patients with endometriosis and investigated the potential function of changed metabolites in granulosa cells. RNA-sequencing indicated that both endometriosis lesions and oxidative stress in mice induced abnormalities of reactive oxidative stress, steroid hormone biosynthesis, and lipid metabolism. The mouse model and women with endometriosis showed altered lipid metabolism. Nontargeted metabolite profiling of follicular fluid from endometriosis and male-factor infertility patients by liquid chromatography mass spectrometry identified 55 upregulated and 67 downregulated metabolites. These differential metabolites were mainly involved in steroid hormone biosynthesis and glycerophospholipid metabolism. Phosphatidylinositol (PI 16:0/18:2) was significantly elevated in follicular fluid from endometriosis patients compared with controls (p < 0.05), while lysophosphatidylinositol (LPI 18:2, 20:2, 18:1, 20:3 and 18:3) was reduced (p < 0.05). Upregulated PI and downregulated LPI correlated with oocyte retrieval number and mature oocyte number. LPI inhibited cellular reactive oxidative stress induced by hemin in granulosa cells. Cell proliferation inhibition, senescence, and apoptosis induced by hemin were partially reversed by LPI. Moreover, LPI administration rescued hemin blocking of cumulus-oocyte complex expansion and stimulated expression of ovulation-related genes. Transcriptomic Switching mechanism at 5' end of the RNA transcript sequencing and western blot revealed that LPI effects on granulosa cells were associated with its regulation of MAPK-ERK1/2 signaling, which was suppressed in the presence of hemin. In conclusion, our results revealed the dysregulation of lipid metabolism in endometriotic follicles. LPI may represent a novel agent for in vitro follicular culture that reverses the excessive oxidative stress from endometriotic lesions. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Endometriose , Infertilidade , Humanos , Feminino , Masculino , Animais , Camundongos , Endometriose/metabolismo , Transcriptoma , Hemina/metabolismo , Metabolômica , Infertilidade/complicações , Metabolismo dos Lipídeos , RNA/metabolismo , Esteroides , Hormônios
8.
Artigo em Chinês | MEDLINE | ID: mdl-36597369

RESUMO

Objective:To analyze the clinical effect of free posterior lateral peroneal artery perforator flap of lower leg in repairing postoperative defect of oropharyngeal carcinoma. Methods:Thirty-six patients with oropharyngeal carcinoma admitted to the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Bengbu Medical College from June 2016 to June 2019 were analyzed and followed up, eighteen patients were treated with free posterior lateral peroneal artery perforator flap of the lower leg to repair the postoperative defects(experimental group), and eighteen patients were treated with free forearm flap(control group). The survival rate of the transplanted flap, the wound stageⅠhealing rate and average hospitalization time were compared between the two groups. Kaplan-Meier method was used to calculate the 1-year and 3-year survival rates of patients after operation, and log-rank test was used to compare the difference between the survival curves of the two groups; The recovery of swallowing and palatopharyngeal closure function of patients in the two groups at 3, 6, 12 and 18 months after operation was calculated and statistically analyzed through the water swallow test and the air blowing method. Results:There was one case of skin flap necrosis in both the experimental group and the control group, and the survival rate was 94.4%. The wound stageⅠhealing rate in the surgical area was 94.4% in both groups. The wound healing rates of the donor area in the experimental group and the control group were 100.0% and 94.4% respectively. The average hospitalization time of the experimental group and the control group was 16.9 days and 17.2 days, respectively, with no significant difference (P>0.05). The overall survival rates of all patients at 1-year and 3-year were 91.2% and 66.5% respectively; The 1-year and 3-year survival rates of the experimental group and the control group were 94.1%, 69.3% and 88.2%, 63.7%, respectively, and there was no significant difference between the two groups (P>0.05). The 1-year and 3-year survival rates of P16+ and P16 - patients were 100.0%, 80.0% and 85.7%, 64.3%, respectively, and there was no significant difference between the two groups (P>0.05). There was no significant difference in the evaluation of swallowing and velopharyngeal closure function between the two groups at 3 and 6 months after operation (P>0.05), but there was a significant difference at 12 and 18 months after operation (P<0.05). Conclusion:The anatomic position of the perforating vessels of the free posterior lateral peroneal artery perforator flap of the lower leg is constant, and it can be prepared into single leaf, multi leaf, chimeric and other flaps according to the tissue defect space. And the concealed supply area can be directly drawn to suture. At the same time, the skin flap has strong plasticity. Therefore, the skin flap can be used as a common skin flap to repair the defects after the operation of oropharyngeal carcinoma.


Assuntos
Carcinoma , Neoplasias Orofaríngeas , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Transplante de Pele/métodos , Perna (Membro)/cirurgia , Retalho Perfurante/cirurgia , Retalho Perfurante/transplante , Neoplasias Orofaríngeas/cirurgia , Artérias/cirurgia , Carcinoma/cirurgia , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento
9.
Endocrinology ; 164(2)2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36524678

RESUMO

The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1ß is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein ß pathways. However, this amplification of ovulation by IL-1ß does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the effect of oxidative stress and IL-1ß expression on endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing (ChIP-Seq) of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1ß-receptor that suppresses IL-1ß-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1ß addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility.


Assuntos
Endometriose , Infertilidade Feminina , Animais , Feminino , Camundongos , Endometriose/complicações , Endometriose/genética , Endometriose/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células da Granulosa/metabolismo , Histonas/metabolismo , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Receptores Tipo II de Interleucina-1/genética , Receptores Tipo II de Interleucina-1/metabolismo , Humanos
10.
Dis Markers ; 2021: 1923636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504626

RESUMO

OBJECTIVE: To find risk markers and develop new clinical predictive models for the differential diagnosis of hand-foot-and-mouth disease (HFMD) with varying degrees of disease. METHODS: 19766 children with HFMD and 64 clinical indexes were included in this study. The patients included in this study were divided into the mild patients' group (mild) with 12292 cases, severe patients' group (severe) with 6508 cases, and severe patients with respiratory failure group (severe-RF) with 966 cases. Single-factor analysis was carried out on 64 indexes collected from patients when they were admitted to the hospital, and the indexes with statistical differences were selected as the prediction factors. Binary multivariate logistic regression analysis was used to construct the prediction models and calculate the adjusted odds ratio (OR). RESULTS: SP, DP, NEUT#, NEUT%, RDW-SD, RDW-CV, GGT, CK/CK-MB, and Glu were risk markers in mild/severe, mild/severe-RF, and severe/severe-RF. Glu was a diagnostic marker for mild/severe-RF (AUROC = 0.80, 95% CI: 0.78-0.82); the predictive model constructed by temperature, SP, MOMO%, EO%, RDW-SD, GLB, CRP, Glu, BUN, and Cl could be used for the differential diagnosis of mild/severe (AUROC > 0.84); the predictive model constructed by SP, age, NEUT#, PCT, TBIL, GGT, Mb, ß2MG, Glu, and Ca could be used for the differential diagnosis of severe/severe-RF (AUROC > 0.76). CONCLUSION: By analyzing clinical indicators, we have found the risk markers of HFMD and established suitable predictive models.


Assuntos
Biomarcadores/análise , Doença de Mão, Pé e Boca/diagnóstico , Transtornos Mentais/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença , China , Feminino , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
11.
Biomed Res Int ; 2020: 1216907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32051822

RESUMO

PURPOSE: To examine the benefits of different numbers of 1064-nm Nd-YAG laser treatments in patients with onychomycosis. METHODS: This was a pilot study of patients with onychomycosis who were divided into three groups: four treatment sessions (group A), eight sessions (group B), and 12 sessions (group C). Only infected nails of degrees II-III (Scoring Clinical Index for Onychomycosis) were included. Treatment was given once a week using a long-pulse Nd-YAG 1064-nm laser. Patients were followed at 8, 16, and 24 weeks after the first treatment. Side effects were recorded. RESULTS: Treatments were completed for 442 nails in 102 patients. The efficacy rates at 8, 16, and 24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%, 41.7%, and 44.0% for group B; and 27.7%, 50.0%, and 55.4% for group C, respectively. There was a significant difference in the efficacy rate at 24 weeks (P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all. CONCLUSIONS: The 1064-nm Nd-YAG laser had clinical benefits against onychomycosis. Higher numbers of treatments provided better long-term (24-week) benefits, but had no impact on the short-term outcomes. The efficacy of laser treatment on degree II onychomycosis was better than for degree III.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Onicomicose/radioterapia , Pulso Arterial/métodos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/fisiologia , Onicomicose/diagnóstico por imagem , Onicomicose/patologia , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
12.
Int J Phytoremediation ; 22(10): 1009-1018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32064907

RESUMO

A greenhouse pot experiment was conducted to assess the effects of biochar (BC) and arbuscular mycorrhizal fungus (AMF)-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the plant growth and Cd/Pb accumulation by corn grown in the soils artificially contaminated with 5 mg Cd and 300 mg Pb kg-1 soil. The single AMF inoculation and combined usage of AMF and BC evidently improved the P contents of maize. Furthermore, the combined use of AMF and BC produced pronounced positive effect on corn growth, and the shoot biomass in Gv + BC group was 9.85-fold higher than that of the control. Meanwhile, the single BC addition and combined utilization of AMF and BC significantly reduced Cd and Pb concentrations in maize, and the greater reduces were found in the combined utilization, and the lowest Cd concentration of shoot was appeared in Gv + BC group. The single BC addition and combined application of AMF and BC significantly increased soil pH, and reduced soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd/Pb. This study demonstrated a synergistic effect between AMF (Gv, Fm, Ri) and BC on improving maize growth and decreasing Cd/Pb accumulation in maize, and the combined use of Gv and BC brought the most pronounced effect, which could provide a feasible strategy for safe production of maize from Cd/Pb-polluted soils.


Assuntos
Micorrizas , Poluentes do Solo/análise , Biodegradação Ambiental , Cádmio/análise , Carvão Vegetal , Chumbo , Raízes de Plantas/química , Solo , Zea mays
13.
Front Endocrinol (Lausanne) ; 11: 583229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584536

RESUMO

Aim: This study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA). Methods: Synovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Results: Immunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P<0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P<0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P<0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P<0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P<0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently. Conclusion: VDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.


Assuntos
Apoptose , Artrite Reumatoide/patologia , Fibroblastos/patologia , Osteoartrite/patologia , Sinoviócitos/patologia , Proteína de Ligação a Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Idoso , Artrite Reumatoide/metabolismo , Artrite Reumatoide/terapia , Estudos de Casos e Controles , Ciclo Celular , Proliferação de Células , Células Cultivadas , Terapia Combinada , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Osteoartrite/terapia , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Vitamina D/farmacologia
14.
Biochem Biophys Res Commun ; 518(3): 560-564, 2019 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-31451221

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. The imbalance of T helper type 1 (Th1) and Th2 immune responses contributes to the pathogenesis of this disease. Germacrone is a major bioactive component isolated from Rhizoma Curcuma with multiple bioactivities including anti-inflammation. However, the role and mechanism of germacrone in RA are still unknown. Collagen-induced arthritis (CIA) model was established in male DBA/1 J mice by two immunizations with chicken collagen II. Germacrone was orally administered once per day starting on the day of second immunization for 3 weeks. Arthritis scoring was evaluated every 3 days after second immunization. H&E staining was used for histopathological examination. Levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-4 in serum and synovial tissues of mice were detected by ELISA. Th1 and Th2 cell percentage in mouse spleens was analyzed by flow cytometry. IκB and phosphorylation of NF-κB p65 (p-p65) expression in mouse synovial tissues was assayed by Western blot. We found germacrone treatment significantly reduced arthritis score and inflammation in CIA mice. Levels of TNF-α and IFN-γ were elevated, and IL-4 reduced, in the serum and synovial tissues of CIA mice. Germacrone partially reversed levels of these cytokines. Moreover, germacrone decreased the ratio of Th1 to Th2 cells in mouse spleens. Additionally, germacrone remarkably enhanced IκB expression, but suppressed p-p65 level in CIA mice. Taken together, these results suggest that germacrone alleviated the progression of arthritis that might be related to the regulation of Th1/Th2 balance and inactivation of NF-κB pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , NF-kappa B/imunologia , Sesquiterpenos de Germacrano/uso terapêutico , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Colágeno , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Células Th1/imunologia , Células Th1/patologia , Células Th2/imunologia , Células Th2/patologia
16.
Int J Phytoremediation ; 21(9): 857-865, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30919656

RESUMO

Little attention has been paid to the combined use of arbuscular mycorrhizal fungus (AMF) and steel slag (SS) for ameliorating heavy metal polluted soils. A greenhouse pot experiment was conducted to study the effects of SS and AMF-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on plant growth and Cd, Pb uptake by maize grown in soils added with 5 mg Cd kg-1 and 300 mg Pb kg-1 soil. The combined usage of AMF and SS (AMF + SS) promoted maize growth, and Gv + SS had the most obvious effect. Meanwhile, single SS addition and AMF + SS decreased Cd, Pb concentrations in maize, and the greater reductions were found in combined utilization, and the lowest Cd, Pb concentrations of maize appeared in Gv + SS. Single SS amendment and AMF + SS enhanced soil pH and decreased soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Pb concentrations. Furthermore, alone and combined usage of AMF and SS increased contents of soil total glomalin. Our research indicated a synergistic effect between AMF and SS on enhancing plant growth and reducing Cd, Pb accumulation in maize, and Gv + SS exerted the most pronounced effect. This work suggests that AMF inoculation in combination with SS addition may be a potential method for not only phytostabilization of Pb-Cd-contaminated soil but maize safety production.


Assuntos
Micorrizas , Poluentes do Solo/análise , Biodegradação Ambiental , Cádmio/análise , Chumbo , Raízes de Plantas , Aço , Zea mays
17.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1106-1107: 19-25, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30639946

RESUMO

The presence of α­dicarbonyl compounds (α-DCs) in vivo has been associated with the development of complications of diabetes mellitus (DM) and also with other chronic diseases. Therefore, quantitative analysis of α-DCs in body fluids is crucial to understand their roles in the formation of these chronic diseases. We established in this study a practical HPLC-UV method to measure 3­deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane­2,3­dione (PD) in blood plasma using 4­(2,3­dimethyl­6­quinoxalinyl)­1,2­benzenediamine (DQB) as a derivatizing reagent. The derivatizing reaction could be carried out quickly under mild conditions and the HPLC determination is simple, sensitive, and easy to operate. The recoveries of the α-DCs are between 85.26% and 110.20% (intra-day) and 87.25% and 103.18% (inter-day); the RSDs are between 1.28% and 5.69% (intra-day) and 2.26% and 6.34% (inter-day). We found the plasma levels of 3-DG, GO, and MGO in the diabetic patients are all significantly higher than those in healthy subjects. The results also show that the contents of GO and MGO in diabetic nephropathy (DN) patients are both significantly higher than those in simple T2DM patients. Moreover, it is found for the first time that the plasma level of GO might be a potential predictor of DN. The developed method would be useful for the measurements of the plasma α-DCs and the data acquired could be informative in the diagnosis of DM complications.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Idoso , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Desoxiglucose/análogos & derivados , Desoxiglucose/sangue , Nefropatias Diabéticas/diagnóstico , Diacetil/sangue , Feminino , Glioxal/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Aldeído Pirúvico/sangue
18.
Epidemiology ; 30(1): 93-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30063539

RESUMO

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.


Assuntos
Dieta , Neoplasias de Cabeça e Pescoço/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Intervalos de Confiança , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reprodutibilidade dos Testes , Estados Unidos/epidemiologia
19.
ACS Appl Mater Interfaces ; 10(16): 13264-13273, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29616788

RESUMO

Studies on the development of fluorescent organic molecules with different emission colors for imaging of organelles and their biomedical application are gaining lots of focus recently. Here, we report two cationic organochalcogens 1 and 2, both of which exhibit very weak green emission (Φ1 = 0.12%; Φ2 = 0.09%) in dilute solution as monomers, but remarkably enhanced green emission upon interaction with nucleic acids and large red-shifted emission in aggregate state by the formation of excimers at high concentration. More interestingly, the monomer emission and excimer-like emission can be used for dual color imaging of different organelles. Upon passively diffusing into cells, both probes selectively stain nucleoli with strong green emission upon 488 nm excitation, whereas upon 405 nm excitation, a completely different stain pattern by staining lysosomes (for 1) or mitochondria (for 2) with distinct red emission is observed because of the highly concentrated accumulation in these organelles. Studies on the mechanism of the accumulation in lysosomes (for 1) or mitochondria (for 2) found that the accumulations of the probes are dependent on the membrane permeabilization, which make the probes have great potential in diagnosing cell damage by sensing lysosomal or mitochondrial membrane permeabilization. The study is demonstrative, for the first time, of two cationic molecules for dual-color imaging nucleoli and lysosomes (1)/mitochondria (2) simultaneously in live cell based on monomer and excimer-like emission, respectively, and more importantly, for diagnosing cell damage.


Assuntos
Calcogênios/química , Cátions , Sobrevivência Celular , Cor , Corantes Fluorescentes , Lisossomos , Mitocôndrias
20.
Inorg Chem ; 56(13): 7307-7311, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28613850

RESUMO

Visible-light driven reduction of CO2 into chemical fuels has attracted enormous interest in the production of sustainable energy and reversal of the global warming trend. The main challenge in this field is the development of efficient, selective, and economic photocatalysts. Herein, we report a Co(II)-based homogeneous catalyst, [Co(NTB)CH3CN](ClO4)2 (1, NTB = tris(benzimidazolyl-2-methyl)amine), which shows high selectivity and stability for the catalytic reduction of CO2 to CO in a water-containing system driven by visible light, with turnover number (TON) and turnover frequency (TOF) values of 1179 and 0.032 s-1, respectively, and selectivity to CO of 97%. The high catalytic activity of 1 for photochemical CO2-to-CO conversion is supported by the results of electrochemical investigations and DFT calculations.

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