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1.
Clin Biochem ; 125: 110719, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38316335

RESUMO

BACKGROUND: Increased cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) values are attributed to immune activation, lymphoid cell turnover and release of tissue destruction in the central nervous system (CNS). We investigated plasma and CSF ß2-MG levels in adult patients with viral encephalitis/meningitis and their correlations with clinical parameters. METHOD: CSF samples from 26 patients with viral encephalitis/meningitis were collected. Moreover, 24 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 22 enrolled patients and 20 healthy individuals were collected. The ß2-MG levels were measured by immunoturbidimetry on an automatic biochemical analyzer. Clinical data were extracted from an electronic patient documentation system. RESULT: CSF levels of ß2-MG, adenosine deaminase (ADA), white blood cell (WBC), lactate dehydrogenase (LDH), protein and lactate were significantly increased in patients with viral encephalitis/meningitis respectively (p < 0.001, p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.013). In contrast, no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were weakly correlated with WBC (r = 0.426, p = 0.030), lymphocyte percentage (r = 0.599, p = 0.018), ADA (r = 0.545, p = 0.004) and LDH (r = 0.414, p = 0.036), but not with lactate (r = 0.381, p = 0.055), protein (r = 0.179, p = 0.381) and plasma levels of ß2-MG (r = -0.156, p = 0.537) in viral encephalitis/meningitis patients. CONCLUSION: CSF ß2-MG may be a potential inflammatory marker for viral encephalitis/meningitis in adult patients diagnosed with viral encephalitis/meningitis.


Assuntos
Encefalite Viral , Encefalite , Meningite , Adulto , Humanos , Meningite/líquido cefalorraquidiano , Meningite/diagnóstico , Ácido Láctico , Plasma , Líquido Cefalorraquidiano
2.
Front Nephrol ; 3: 1105933, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675352

RESUMO

Introduction: Immunoglobulin A nephropathy (IgAN) presents various clinical manifestations and pathological phenotypes. Approximately 5% of patients with IgAN present with early onset nephrotic syndrome, mild mesangial lesions, and diffuse foot process effacement of podocytes, which resemble minimal change disease (MCD). These patients are defined as MCD-IgAN. Whether MCD-IgAN is a special type of IgAN or simply MCD accompanied by IgA deposition remains controversial. Methods: A total of 51 patients diagnosed with MCD-IgAN at Beijing Anzhen Hospital from January 2010 to September 2022 were recruited. The clinical and pathological characteristics of IgA-MCD were analyzed. Patients with IgAN but without MCD (non-MCD-IgAN) and healthy participants were enrolled as controls. Galactose-deficient immunoglobulin A1 (Gd-IgA1) and complement C3 were detected both in the circulation and in renal tissues. Results: We found that the levels of serum Gd-IgA1 were lower in participants with MCD-IgAN than in those with non-MCD-IgAN, but higher than in healthy participants. Gd-IgA1 was rarely deposited in the glomeruli of participants with MCD-IgAN, with a positive rate of only 13.7% (7/51); in contrast, the positive rate in participants with non-MCD-IgAN was 82.4% (42/51). Among renal Gd-IgA1-positive patients, Gd-IgA1 and immunoglobulin A (IgA) colocalized along the glomerular mesangial and capillary areas. Interestingly, we found that the circulating levels of complement C3 were significantly higher in participants with MCD-IgAN than in participants with non-MCD-IgAN. In addition, the intensity of C3c in glomeruli in participants with MCD-IgAN was significantly weaker than in participants with non-MCD-IgAN. Conclusions: Our study suggests that, in MCD-IgAN, most of the IgA that is deposited on glomeruli is not the same pathogenic Gd-IgA1 as found in general IgAN. Complement activation both in the circulation and in the renal locality was much weaker in MCD-IgAN than in non-MCD-IgAN. Our study suggests that IgAN with MCD might be MCD with coincidental IgA deposition.

3.
Front Med (Lausanne) ; 9: 945913, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991640

RESUMO

Introduction: IgA nephropathy (IgAN) encompasses a wide range of clinical and histology features. Some patients present without hematuria, with or without hypertension, still rapidly progress in renal function. Renal pathology of this part of patients were predominant intrarenal arteriolar lesions, rarely presented glomerular proliferative lesions. We aim to investigate the clinical and pathological characteristics and prognosis of these IgAN patients and initially explore whether the abnormal activation of complement is involved in the intrarenal arteriolar lesions of IgAN. Methods: A total of 866 patients with renal biopsy-proven IgAN diagnosed at Beijing Anzhen Hospital were recruited. IgAN patients without intrarenal arteriolar lesions and proliferative lesions were excluded (n = 115), the rest were divided into arteriolar lesions group (n = 202) and proliferative lesions group (n = 549). Among them, 255 patients were regularly followed up for at least 1 year. Renal biopsy tissues of 104 IgAN patients were stained for complement components by immunohistochemistry and immunofluorescence. Results: Compared with proliferative lesions group, the arteriolar lesions group experienced high percentage of hypertension (p = 0.004), low percentage of gross hematuria (p = 0.001), microscopic hematuria (p < 0.001) and less initial proteinuria (p = 0.033). Renal survival between the two groups was not significantly different (p = 0.133). MBL, C4d, FH and FHR5, C3c, and MAC deposited on intrarenal arteriole in arteriolar lesions group. Compare with the proliferative lesion group, the arteriolar lesions group exhibited a higher intensity of C3c deposition on the intrarenal arterioles (p = 0.048). C3c and CD31 co-deposited on intrarenal arterioles area in patients with intrarenal arteriolar lesions. Conclusion: Renal survival of the IgAN patients in arteriolar lesions group was not better than those in proliferative lesions group. Abnormal activation of complement may be involved in the pathogenesis of arteriolar damage through the injury of endothelial cells in this clinical phenotype of IgAN.

4.
Inorg Chem ; 60(20): 15659-15666, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34590478

RESUMO

The fractional oxidation state [M(dmit)2] (dmit2- = 2-thioxo-1, 3-dithiole-4, 5-dithiolate) salts have long attracted attention in the molecular metal area owing to high conductivity and even superconductivity. In this study, we achieved a mixed-valence salt (1) of [Ni(dmit)2]0.5- with monovalent 1,3-N,N-dimethyl-imidazolium (DiMIm+) by a solvent evaporation approach under ambient conditions. The mixed valence of [Ni(dmit)2]0.5- has been characterized by an analysis of the IR spectrum and crystal structure. In the crystal structure of 1, two [Ni(dmit)2]0.5- anions overlap in an eclipsed mode to form a [Ni(dmit)2]21- dimer, featuring a radical bearing an S = 1/2 spin; the dimeric radicals stack into a column along the b axis, and the adjacent columns connect together via the lateral-to-lateral S···S contacts along the a axis, and through the head-to-head S···S contacts along the [101] direction. Salt 1 shows the magnetic behavior of an S = 1/2 Heisenberg antiferromagnetic uniform linear chain with J/kB = -47.5(4) K and a semiconducting feature with σ = 2.52 × 10-3 S cm-1 at 293 K, 2.32 × 10-2 S cm-1 at 373 K, and Ea = 0.22 eV, as well as broadband photoconductivity under irradiation of green and white lights. This study suggests the possibility of designing new photoconductors based on the mixed-valence [Ni(dmit)2]0.5- salt.

5.
Kidney Int Rep ; 6(2): 404-413, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33615066

RESUMO

INTRODUCTION: Immunoglobulin A nephrology (IgAN), characterized by co-deposition of IgA and complement components, is an activation of complement system involved disease. Factor H-related protein 5 (FHR-5) antagonized the ability of factor H to negatively regulate C3 activation, which leads to overactivation of the alternative pathway. Here we explore the relationship of intensity of glomerular FHR-5 deposition and severity of IgAN. METHODS: Renal staining of FHR-5 was detected by immunofluorescence, and plasma FHR-5 was detected by enzyme-linked immunosorbent assay in 56 patients with IgAN. The relationship of intensity of glomerular FHR-5 and clinical and pathologic features of these patients were further analyzed. RESULTS: Glomerular staining for FHR-5 was observed in a predominantly mesangial pattern in 32 biopsy specimens (57.1%). FHR-5 co-deposited with IgA and C3c in glomerular mesangial and capillary area in patients with IgAN. Patients with IgAN with Oxford endocapillary hypercellularity (P = 0.007) and segmental glomerulosclerosis (P = 0.049) presented with greater intensity of FHR-5 deposition. There were more cases with 2+ and 3+ FHR-5 staining in cohorts of 2+ and 3-4+ mesangial C3 deposition (P = 0.034) and IgA deposition (P = 0.019). Interestingly, the glomerular FHR-5 depositions were more abundant in male versus female in patients with IgAN (P = 0.002). Besides, circulating FHR-5 levels were elevated in patients with IgAN compared with healthy control subjects. Plasma FHR-5 levels were significantly higher in patients with mesangial hypercellularity at diagnosis than those with nonmesangial hypercellularity. CONCLUSIONS: We found that glomerular intensity of FHR-5 deposition could indicate the severity of histologic lesions of IgAN.

6.
BMC Nephrol ; 22(1): 42, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509125

RESUMO

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). CASE PRESENTATIONS: Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. CONCLUSIONS: LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.


Assuntos
Nefropatias/etiologia , Mieloma Múltiplo/complicações , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
7.
Aging (Albany NY) ; 12(19): 19335-19351, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031059

RESUMO

In atherosclerosis, upregulated TILRR (FREM1 isoform 2) expression increases immune cell infiltration. We hypothesized that TILRR expression is also correlated with cancer progression. By analyzing data from Oncomine and the Tumor Immune Estimation Resource, we found that TILRR mRNA expression was significantly lower in breast cancer tissue than adjacent normal tissue. Kaplan-Meier survival analysis and immunohistochemical staining revealed shortened overall survival and disease-free survival in patients with low TILRR expression. TILRR transcript expression was positively correlated with immune score, immune cell biomarkers and the expression of CXCL10 and CXCL11. TILRR expression was also positively correlated with CD8+ and CD4+ T-cell infiltration. These correlations were verified using the ESTIMATE algorithm, gene set enrichment analysis and Q-PCR. We concluded that impaired TILRR expression is correlated with breast cancer prognosis and immune cell infiltration.

8.
Sci Rep ; 10(1): 8616, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451462

RESUMO

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.


Assuntos
Povo Asiático/genética , Mucina-1/genética , Rim Policístico Autossômico Dominante/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Mutação da Fase de Leitura , Testes Genéticos , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/etiologia , Rim/diagnóstico por imagem , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Linhagem , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/patologia , Sequências de Repetição em Tandem/genética , Ultrassonografia , Ácido Úrico/urina , Sequenciamento do Exoma
9.
J Cancer ; 10(18): 4178-4188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413736

RESUMO

Gastric cancer (GC) is a leading global health problem as it is the fifth most common cancer type and the third most common cause of cancer-related deaths worldwide. In most areas of the world, the incidence rate of GC is 1.5- to 3-fold higher in males than in females. The androgen receptor (AR) is an independent adverse prognostic factor in patients with GC. However, the mechanism by which AR regulates the progression of GC remains unclear. In this study, we found that AR expression was upregulated in 6/8 GC cell lines, and this expression was higher than that in immortalized gastric cells. AR expression was also higher in GC tissues than in adjacent tissues. Moreover, the ectopic expression of AR promoted the colony formation ability, migration and invasion of GC cells. In contrast, AR knockdown had the opposite effects on GC cell lines. Remarkably, we found that AR regulated cell cycle-related kinase (CCRK) expression through transcriptional mechanisms. The AR-CCRK axis promoted GC development through the phosphorylation of GSK3ß and ß-catenin. Furthermore, TCGA data revealed that high expression of AR or CCRK was related to poor prognosis in GC patients. The prognosis was significantly worse in patients with concurrent high AR and CCRK expression than in patients with low AR and CCRK expression. In conclusion, our study demonstrated that AR and CCRK acted as oncogenes in GC progression. However, their clinical roles require further exploration.

10.
Medicine (Baltimore) ; 98(31): e16571, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374024

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.


Assuntos
Crioglobulinemia/complicações , Doença Relacionada a Imunoglobulina G4/complicações , Sialadenite/complicações , Crioglobulinemia/tratamento farmacológico , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Sialadenite/tratamento farmacológico
11.
Mol Cancer Ther ; 17(12): 2610-2621, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30224431

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common and deadly human cancers. The 5-year survival rate is very low. Unfortunately, there are few efficacious therapeutic options. Until recently, Sorafenib has been the only available systemic drug for advanced HCC. However, it has very limited survival benefits, and new therapies are urgently needed. In this study, we investigated the anti-HCC activity of carfilzomib, a second-generation, irreversible proteasome inhibitor, as a single agent and in combination with sorafenib. In vitro, we found that carfilzomib has moderate anticancer activity toward liver cancer cells, but strongly enhances the ability of sorafenib to suppress HCC cell growth, proliferation, migration, invasion, and survival. Remarkably, the drug combination exhibits even more potent antitumor activity when tested in animal tumor models. Mechanistically, the combined treatment activates caspase-dependent and endoplasmic reticulum stress/CHOP-mediated apoptotic pathways, and suppresses epithelial-mesenchymal transition. In conclusion, our results demonstrate that the combination of carfilzomib and sorafenib has synergistic antitumor activities against HCC, providing a potential therapeutic strategy to improve the mortality and morbidity of HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Oligopeptídeos/farmacologia , Sorafenibe/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Cancer ; 9(16): 2807-2816, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123349

RESUMO

Using genome-wide screening and TCGA-based data analysis, we identified a DNA methylation-related gene named metallothionein-1G (MT1G), which may play an important role in hepatocellular carcinoma (HCC). In this study, we found that MT1G expression was silenced in 4/6 HCC cell lines and negatively related to aberrant promoter hypermethylation. Its mRNA level was restored with demethylation treatment. Moreover, MT1G downregulation at both the transcriptional and protein level was also detected in 8 pairs of clinical HCC samples compared with its expression in adjacent normal tissues. Ectopic expression of MT1G in silenced HCC cell lines inhibited colony formation, suppressed cell migration and invasion, and repressed xenograft tumor growth in nude mice. In contrast, knockdown of MT1G by short hairpin RNA showed the opposite effect on cell proliferation and the malignant phenotype. Moreover, our data showed that MT1G suppressed tumor invasion and metastasis mainly through regulating the expression of proteins in the matrix metalloproteinase family (MMP) and modulating the epithelial-mesenchymal transition (EMT) process. To our surprise, the data from TCGA showed that hypermethylation of MT1G is associated with good survival of HCC patients. In conclusion, our study demonstrated that MT1G acts as a tumor suppressor gene in HCC development, but its clinical potential in HCC requires further evaluation.

13.
Cell Cycle ; 16(18): 1673-1682, 2017 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-28841361

RESUMO

p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Progressão da Doença , Transição Epitelial-Mesenquimal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ribonucleotídeo Redutases/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Análise de Sobrevida
14.
Huan Jing Ke Xue ; 38(5): 2052-2058, 2017 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965113

RESUMO

Immobilization of activated sludge was used to further remove nitrogen from secondary effluent. Intermittent sequencing batch reactor experiments were conducted to measure nitrogen removal in synthetic wastewater with initial total nitrogen concentrations (TN) of 10-45 mg·L-1 and C/N ratio of 1.78-10, and microbial community characteristic of embedding beads was investigated. When the packing ratio of embedding beads was 10%, and the temperature of wastewater, dissolved oxygen (DO), initial concentration of chemical oxygen demand (COD) were maintained at 10-15℃, 2-4 mg·L-1, and 80-100 mg·L-1, respectively, the results showed that the maximum total nitrogen removal loads ranged from 7.78 to 23.18 mg·(L·h)-1during the stable phase. SEM observations showed that the embedding beads were highly porous and microorganisms adhered to the interior and external surface of embedding beads, demonstrating that embedding beads acted as an ideal support material. Based on high-throughput sequencing analysis, the structure of microbial communities in the beads'interior and exterior changed significantly compared with embedding activated sludge. The advantage of denitrifying bacteria in embedding beads was obvious and the microbial diversity was good. Some microorganisms which can conduct both heterotrophic nitrification and aerobic denitrification, were identified. These processes may facilitate pathways for untraditional biological denitrification in the beads'interior.


Assuntos
Desnitrificação , Nitrogênio/isolamento & purificação , Esgotos/microbiologia , Águas Residuárias , Reatores Biológicos , Nitrificação
16.
PLoS One ; 11(2): e0149242, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890569

RESUMO

OBJECTIVE: To investigate the inhibitory effect of Hirsutella sinensis (HS) on epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by aristolochic acid (AA) and its possible mechanism. METHODS: 18 male Sprague-Dawley rats were randomly and equally divided into the following 3 groups: AA group, AA+HS group and control group. Urinary protein excretion and creatinine clearance (CCr) were measured. All rats were sacrificed at the end of 12th week. The pathological examination of renal tissue was performed and the mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), cytokeratin-18 and Snail in renal cortex were determined by real time quantitative PCR and immunohistochemical staining respectively. In addition, human renal proximal tubule epithelial cells line (HKC) was divided into the following 4 groups: AA group, AA+HS group, HS control group and control group. The above mRNA and protein expression in HKC was determined by real time quantitative PCR and Western blot respectively. RESULTS: (1) CCr was significantly decreased, and the urinary protein excretion and relative area of renal interstitial fibrosis were significantly increased in the rats of AA and AA+HS group compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly lightened in the rats of AA+HS group compared to those in AA group (P<0.05). (2) The mRNA and protein expression of TGF-ß1, α-SMA and Snail was significantly up-regulated and the expression of cytokeratin-18 was significantly down-regulated in the rat renal cortex as well as in the cultured HKC cells in AA and AA+HS groups compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly alleviated in AA+HS group compared to those in AA group (P<0.05 or P<0.01). (3) Knockdown endogenous Snail expression by siRNA could ameliorate AA-induced EMT of HKC cells, while overexpression of Snail by plasmid transfection diminished the antagonistic effect of HS on AA-induced EMT. These results suggest Snail might be a potential target of HS effect. CONCLUSION: HS is able to antagonize, to some extent, tubular EMT and renal interstitial fibrosis caused by AA, which might be related to its inhibitory effects on the TGF-ß1 and Snail expression.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Ascomicetos/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Túbulos Renais/citologia , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta1/genética , Actinas/genética , Actinas/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Queratina-18/genética , Queratina-18/metabolismo , Córtex Renal/efeitos dos fármacos , Córtex Renal/metabolismo , Córtex Renal/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
17.
Biodegradation ; 25(6): 777-86, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25073616

RESUMO

In this study, an advanced wastewater treatment process, the denitrifying phosphorus/side stream phosphorus removal system (DPR-Phostrip), was developed for the purpose of enhancing denitrifying phosphorus removal. The enrichment of denitrifying phosphorus-accumulating organisms (DPAOs) and the microbial community structure of DPR-Phostrip were evaluated by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), and the metabolic activity of seed sludge and activated sludge collected after 55 days of operation were evaluated by Biolog™ analysis. This experimental study of DPR-Phostrip operation showed that nutrients were removed effectively, and denitrifying phosphorus removal was observed during the pre-anoxic period. PCR-DGGE analysis indicated that DPR-Phostrip supported DPAO growth while inhibiting PAOs and GAOs. The major dominant species in DPR-Phostrip were Bacteroidetes bacterium, Saprospiraceae bacterium, and Chloroflexi bacterium. Moreover, the functional diversity indices calculated on the basis of Biolog analysis indicated that DPR-Phostrip had almost no effect on microbial community diversity but was associated with a shift in the dominant species, which confirms the results of the PCR-DGGE analysis. The results for average well color development, calculated via Biolog analysis, showed that DPR-Phostrip had a little impact on the metabolic activity of sludge. Further principal component analysis suggested that the ability to utilize low-molecular-weight organic compounds was reduced in DPR-Phostrip.


Assuntos
Biodegradação Ambiental , Fósforo/metabolismo , Esgotos/microbiologia , Reatores Biológicos/microbiologia , Eletroforese em Gel de Gradiente Desnaturante , Rios/química , Rios/microbiologia
18.
Environ Technol ; 34(9-12): 1593-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24191494

RESUMO

A laboratory-scale novel Sludge Reduction Reactor with Arc Guide Plate (SRR) for sludge process reduction was developed in this study. Pollutant removal efficiency and biomass yield for domestic sewage treatment in the Anaerobic/Anoxic/Oxic-SRR (A2/O-SRR) process were compared with performances in a control A2/O process. One of the competitive advantages in the SRR was that part of the inert suspended solids (ISS) could be separated and discharged out of system with flux at the bottom of the SRR. Mixed liquid volatile suspended solids (MLVSS) in the A2/O-SRR system also could be steadily kept at a good level under a relatively long solid retention time. The average MLVSS/mixed liquor suspended solids (MLSS) ratio of 77.5% in the A2/O-SRR was higher than that in the A2/O process. Average removal rates of chemical oxygen demand (COD), total nitrogen (TN) and NH4(+) showed little difference, while total phosphorous (TP) removal efficiency in the A2/O-SRR decreased slightly (81.89% in the A2/O-SRR and 86.50% in the A2/O process) due to the reduction of sludge discharge. The A2/O-SRR system demonstrated a considerable sludge reduction effect, with the sludge reduction ratio of 43.8%, lower solid volume index and higher dehydrogenase activity (DHA) value in comparison to the control A2/O system. The mainly mechanisms of sludge reduction in the SRR have been proved to be the uncoupling effect under the condition of anaerobic/oxic circulation and the sludge lysis with the lack of substrate.


Assuntos
Reatores Biológicos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Nitrogênio , Oxigênio/análise , Oxigênio/química , Fósforo
19.
Zhonghua Yi Xue Za Zhi ; 93(10): 764-7, 2013 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-23755815

RESUMO

OBJECTIVE: To explore the expression of costimulatory molecule CD40 in thyroid tissue of Graves' disease patients and understand its immune pathogenetic significance. METHODS: From January 2008 to December 2011, 8 patients undergoing partial thyroidectomy for Graves' disease (n = 3) or non-toxic goiter (n = 5) at Affiliated Suzhou Hospital of Nanjing Medical University and Third Affiliated Hospital of Soochow University were enrolled. Using the method of immunohistochemistry, the expression of CD40 was detected in their thyroid tissues. Variation in CD40 expression on thyroid follicular (TFC) in primary cultures was analyzed in the absence (no stimulation group) or presence of inflammatory cytokines including interleukin interferon-γ (IFN-γ) (IFN-γ stimulation group), interferon-6 (IL-6) (IL-6 stimulation group)and tumor necrosis factor (TNF)-α (TNF-α stimulation group) with flow cytometry. IFN-γ-stimulated TFC were cultured with agonist CD40 monoclonal antibody (5C11) (IFN-γ + CD40 group) or isotypic mouse IgG (mIgG) antibody (IFN-γ + mIgG group). And the proliferation of TFC was assessed by 3-(4,5)-dimethyl-thiazolyl-3,5-di-phenytetrazoliumromide (MTT) assays for each donor. The production of free triiodothyronine (FT3) and free thyroxine (FT4) and the release of thyroglobulin (Tg) were measured with radioimmunoassays. RESULTS: The expression of CD40 on infiltrated lymphocytes and TFC were detected in Graves' disease but not in non-toxic goiter patient tissues. Compared with no stimulation group (23.7% ± 7.3%), the expression of CD40 on TFC increased in IFN-γ stimulation group (86.4% ± 4.6%), IL-6 stimulation group (90.0% ± 4.2%) and TNF-α stimulation group (87.3% ± 4.2%). Compared with the IFN-γ + mIgG group (0.75 ± 0.06), the TFC proliferation of IFN-γ + CD40 group (1.14 ± 0.14) significantly increased (P < 0.01). The levels of FT3, FT4 and Tg secretion of IFN-γ + CD40 group were (1.10 ± 0.15) pmol/L, (0.80 ± 0.14) pmol/L and (30.23 ± 1.60) µg/L respectively. They were all significantly increased compared with the IFN-γ + mIgG group, of which the FT3, FT4 and Tg production were (0.76 ± 0.07) pmol/L, (0.63 ± 0.09) pmol/L and (21.37 ± 3.22) µg/L respectively (all P < 0.05). CONCLUSIONS: CD40 is abnormally expressed in thyroid tissue of Graves' disease patients. And its costimulatory signal may take part in the immunopathologic mechanism of Graves' disease.


Assuntos
Antígenos CD40/metabolismo , Doença de Graves/metabolismo , Glândula Tireoide/metabolismo , Adulto , Doença de Graves/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Glândula Tireoide/patologia
20.
Huan Jing Ke Xue ; 33(7): 2341-6, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23002611

RESUMO

To understand the composition, sources and contamination characteristics of PAHs in surface water from Jialing River in Chongqing, water samples were collected from 8 different sections in August 2009 and the concentrations of the 16 priority PAHs were determined using GC-MS. The results indicated that the concentration of Sigma PAHs (the total PAHs) in the water body ranged from 467.13 to 987.97 ng x L(-1), with an average concentration of 702.91 ng x L(-1). PAHs concentrations in surface waters were positively correlated with the dissolved organic carbon content. The predominant PAHs in the water body were 2-3 ring PAHs, accounting for 68.90% of Sigma PAHs. The ratios of specific PAHs revealed that the main PAHs source in Cuntan was the combustion of wood and coal, the origin of PAHs in Caotianmen was mostly petrogenic; whereas the main PAHs source in other sampling sections of Jialing River in Chongqing was petroleum combustion. Compared with other areas in China, the PAHs contamination in Jialing River around Chongqing was at a relatively low level, however, the concentrations of BaP in the surface water of 5 sampling sites exceeded the environmental quality standards for surface water in China.


Assuntos
Benzo(a)pireno/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Rios
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