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1.
Nature ; 616(7955): 199-206, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36922595

RESUMEN

In oxygenic photosynthetic organisms, light energy is captured by antenna systems and transferred to photosystem II (PSII) and photosystem I (PSI) to drive photosynthesis1,2. The antenna systems of red algae consist of soluble phycobilisomes (PBSs) and transmembrane light-harvesting complexes (LHCs)3. Excitation energy transfer pathways from PBS to photosystems remain unclear owing to the lack of structural information. Here we present in situ structures of PBS-PSII-PSI-LHC megacomplexes from the red alga Porphyridium purpureum at near-atomic resolution using cryogenic electron tomography and in situ single-particle analysis4, providing interaction details between PBS, PSII and PSI. The structures reveal several unidentified and incomplete proteins and their roles in the assembly of the megacomplex, as well as a huge and sophisticated pigment network. This work provides a solid structural basis for unravelling the mechanisms of PBS-PSII-PSI-LHC megacomplex assembly, efficient energy transfer from PBS to the two photosystems, and regulation of energy distribution between PSII and PSI.


Asunto(s)
Complejos de Proteína Captadores de Luz , Complejo de Proteína del Fotosistema I , Complejo de Proteína del Fotosistema II , Ficobilisomas , Porphyridium , Transferencia de Energía , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/metabolismo , Complejos de Proteína Captadores de Luz/ultraestructura , Fotosíntesis , Complejo de Proteína del Fotosistema I/química , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema I/ultraestructura , Complejo de Proteína del Fotosistema II/química , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema II/ultraestructura , Ficobilisomas/química , Ficobilisomas/metabolismo , Ficobilisomas/ultraestructura , Porphyridium/química , Porphyridium/enzimología , Porphyridium/metabolismo , Porphyridium/ultraestructura , Microscopía por Crioelectrón , Imagen Individual de Molécula
2.
Nature ; 579(7797): 146-151, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32076272

RESUMEN

Photosynthetic organisms have developed various light-harvesting systems to adapt to their environments1. Phycobilisomes are large light-harvesting protein complexes found in cyanobacteria and red algae2-4, although how the energies of the chromophores within these complexes are modulated by their environment is unclear. Here we report the cryo-electron microscopy structure of a 14.7-megadalton phycobilisome with a hemiellipsoidal shape from the red alga Porphyridium purpureum. Within this complex we determine the structures of 706 protein subunits, including 528 phycoerythrin, 72 phycocyanin, 46 allophycocyanin and 60 linker proteins. In addition, 1,598 chromophores are resolved comprising 1,430 phycoerythrobilin, 48 phycourobilin and 120 phycocyanobilin molecules. The markedly improved resolution of our structure compared with that of the phycobilisome of Griffithsia pacifica5 enabled us to build an accurate atomic model of the P. purpureum phycobilisome system. The model reveals how the linker proteins affect the microenvironment of the chromophores, and suggests that interactions of the aromatic amino acids of the linker proteins with the chromophores may be a key factor in fine-tuning the energy states of the chromophores to ensure the efficient unidirectional transfer of energy.


Asunto(s)
Microscopía por Crioelectrón , Transferencia de Energía , Ficobilisomas/química , Ficobilisomas/ultraestructura , Porphyridium/química , Porphyridium/ultraestructura , Proteínas Algáceas/química , Proteínas Algáceas/metabolismo , Proteínas Algáceas/ultraestructura , Modelos Moleculares , Fotosíntesis , Ficobilinas/química , Ficobilinas/metabolismo , Ficobilisomas/metabolismo , Conformación Proteica , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Rhodophyta/química , Rhodophyta/ultraestructura
3.
Funct Integr Genomics ; 23(1): 28, 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36598654

RESUMEN

Increasing evidence has demonstrated that lncRNA plays a significant role in the immunity regulation of gastric adenocarcinoma. However, the immune-related lncRNAs and the prognostic value in immunotherapies remain largely unexplored. We collected immune-related lncRNA and the associated pathways of gastric cancer from the ImmLnc database. The cox regression model is used to analyze the prognostic value of these lncRNAs. Gastric cancer is further divided into different subtypes based on these lncRNAs. Tumor microenvironment analysis, functional enrichment analysis, and genomic alteration analysis are performed for different subtypes. Furthermore, chemotherapeutic and immunotherapeutic sensitivity are also analyzed among different subtypes. Nine lncRNAs are identified as significant regulators of the immune pathway of gastric cancer. Gastric cancer can be classified into 5 subtypes based on these lncRNAs. Tumor microenvironment analysis shows that cluster C3 has the highest immune score and C5 has the lowest score. Functional analysis shows that these subtypes are enriched with distinct biological processes. Genomic analysis shows that LAMA2 mutation is a protective factor in C3 but a risk factor in C5. Furthermore, these subtypes are found to respond distinctly to the same chemotherapeutic and immunotherapeutic drugs. In this study, we analyzed the immune-related lncRNA and identified the crucial role in the regulation of immune properties, biological processes, and immunotherapeutic sensitivity. These findings can improve our understanding of the epigenetic immunoregulation of lncRNA and advance the research of immunotherapy.


Asunto(s)
Adenocarcinoma , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Relevancia Clínica , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Adenocarcinoma/genética , Epigenómica , Microambiente Tumoral/genética
4.
Nature ; 551(7678): 57-63, 2017 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-29045394

RESUMEN

Life on Earth depends on photosynthesis for its conversion of solar energy to chemical energy. Photosynthetic organisms have developed a variety of light-harvesting systems to capture sunlight. The largest light-harvesting complex is the phycobilisome (PBS), the main light-harvesting antenna in cyanobacteria and red algae. It is composed of phycobiliproteins and linker proteins but the assembly mechanisms and energy transfer pathways of the PBS are not well understood. Here we report the structure of a 16.8-megadalton PBS from a red alga at 3.5 Å resolution obtained by single-particle cryo-electron microscopy. We modelled 862 protein subunits, including 4 linkers in the core, 16 rod-core linkers and 52 rod linkers, and located a total of 2,048 chromophores. This structure reveals the mechanisms underlying specific interactions between linkers and phycobiliproteins, and the formation of linker skeletons. These results provide a firm structural basis for our understanding of complex assembly and the mechanisms of energy transfer within the PBS.


Asunto(s)
Microscopía por Crioelectrón , Ficobilisomas/química , Ficobilisomas/ultraestructura , Rhodophyta/química , Rhodophyta/ultraestructura , Proteínas Algáceas/química , Proteínas Algáceas/metabolismo , Proteínas Algáceas/ultraestructura , Transferencia de Energía , Modelos Moleculares , Ficobilisomas/metabolismo , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo
5.
Langmuir ; 38(46): 14192-14199, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36355438

RESUMEN

In this study, a one-step method of polyethylenimine (PEI) cross-linking graphene oxide (GO) was used to prepare a 3D pore-structured adsorbent with abundant amine groups for chemisorption of CO2. The cross-linking of PEI with GO sheets and the vacuum freeze-drying step are the keys to the formation of the 3D pore structure. The results of characterization analysis revealed that the as-prepared adsorbent had a 3D porous structure rich in amine groups. Besides, the adsorption/desorption test showed that the prepared adsorbent has excellent and stable adsorption performance, and the maximum CO2 adsorption capacity is 2.18 mmol/g at 343 K and 10 vol % CO2. Moreover, the adsorption kinetics analysis indicated that the adsorption process was dominated by homogeneous adsorption, and the adsorbent had a strong affinity with CO2. Finally, the correlation analysis shows that the kinetic constants obtained by the Avrami model simulation can be effectively used for the actual CO2 adsorption process design.

6.
Int Arch Occup Environ Health ; 94(1): 69-76, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32561974

RESUMEN

OBJECTIVE: This study aimed to study the relationship between air pollution and stroke (especially emergency stroke) in different regions and determine which air pollutant is the most significantly associated with stroke. METHODS: The number of patients with emergency stroke, air pollutant data and related meteorological indicators were collected from December 2013 to May 2018 for large comprehensive hospitals in Chongqing. The generalized additive model was used to analyse the relationship between air pollution and emergency stroke. RESULTS: After analysis and adjusting for meteorological indicators and day-of-the-week effects, in the one-pollutant model, every 10 µg/m3 increase in ozone(O3) was associated with a 2.482% (95% CI 1.044%, 3.919%) change in emergency strokes within lag0. For males, every 10 µg/m3 increase of O3 contributed to a 0.77% percent greater change compared with females. For the group younger than 60 years, we observed a 1.14% increase in risk with every 10 µg/m3 increase in O3. The group with pre-existing hypertension had a 0.26% higher risk than the group with no pre-existing hypertension with every 10 µg/m3 increase in O3. In two-pollutant model, when O3 was combined with a 10 µg/m3 increase of NO2, it increased the most significant risk of emergency stroke by 0.22%. CONCLUSION: These findings suggest that short-term exposure to O3 within 0 days is associated with emergency outpatient strokes, and younger people (age < 60 years) males and people with hypertension are more sensitive than older people, females and people without pre-existing hypertension.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Hipertensión/epidemiología , Ozono/efectos adversos , Accidente Cerebrovascular/epidemiología , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China/epidemiología , Servicio de Urgencia en Hospital , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dióxido de Nitrógeno/análisis , Ozono/análisis , Material Particulado/análisis , Dióxido de Azufre/análisis , Temperatura , Viento
7.
Lipids Health Dis ; 19(1): 39, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32169116

RESUMEN

BACKGROUND: Obesity is a metabolic imbalance characterized by excessive deposition of white fat. The browning of white fat can effectively treat obesity and related diseases. Although Dlgap1 (Discs, Large (Drosophila) Homolog-Associated Protein 1) is suspected to have an effect on this process, no empirical evidence is available. METHODS: To understand the role of Dlgap1, we cultured white and brown fat cells, then performed overexpression and knockout experiments. RESULTS: We found that Dlgap1 overexpression in brown adipocytes inhibits brown-fat-related gene expression, promotes white-fat-related genes, while also increasing brown-adipocyte proliferation and apoptosis. However, the gene overexpression has no effect on brown adipocyte maturation. Knocking out Dlgap1 in white fat cells promotes the expression and inhibition of brown-fat-related and white-fat-related genes, respectively. Additionally, the knockout inhibits white fat cell proliferation and apoptosis, while also promoting their maturation. CONCLUSIONS: Dlgap1 negatively regulates the browning of white adipocytes by influencing cell proliferation and apoptosis.


Asunto(s)
Adipocitos Marrones/metabolismo , Adipocitos Blancos/metabolismo , Apoptosis/fisiología , Proliferación Celular/fisiología , Proteínas Asociadas a SAP90-PSD95/metabolismo , Adipocitos Marrones/citología , Adipocitos Blancos/citología , Tejido Adiposo Pardo/citología , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/citología , Tejido Adiposo Blanco/metabolismo , Animales , Apoptosis/genética , Western Blotting , Proliferación Celular/genética , Ratones , Proteínas Asociadas a SAP90-PSD95/genética
8.
Exp Cell Res ; 360(2): 375-383, 2017 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-28942023

RESUMEN

Epithelial-mesenchymal transition(EMT) is the main reason for peritoneal fibrosis and the mechanism underlying peritoneal EMT were extensively studied in recent years. Recent researches showed that miRNAs were so important in the development of organ EMT and fibrosis, the role of microRNAs on peritoneal dialysis have also been studied. In the current study, we investigated microRNA-23(miR-23) expression in high glucose(HG) induced EMT in human mesotheial peritoneal cells(HPMCs). We found that HG promoted EMT, which was characterized by the upregulation of mesenchymal markers α-SMA and FN and downregulation of epithelial marker E-cadherin. The expression miR-23 showed a significant upregulation when treated with HG. Enhanced expression of miR-23 could aggravate HG induced EMT by targeting VDR, inhibition of miR-23 in HPMCs could reverse HG induced EMT by targeting VDR. Furthermore, VDRshRNA exacerbated the EMT process and reversed miR-23 inhibitor-attenuated EMT process in HPMCs. These data manifested that miR-23 played a key role in HG-induced EMT of HPMCs by targeting VDR.


Asunto(s)
Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Epitelio/efectos de los fármacos , Glucosa/efectos adversos , MicroARNs/fisiología , Peritoneo/efectos de los fármacos , Receptores de Calcitriol/genética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Epitelio/metabolismo , Epitelio/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/genética , Peritoneo/metabolismo , Peritoneo/patología
9.
Cell Physiol Biochem ; 42(2): 530-536, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28578340

RESUMEN

BACKGROUND/AIMS: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. METHODS: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers. RESULTS: We found that treatment with high Pi levels (1 and 3 mM) activated LC3II expression and promoted autophagic flux in VSMCs. Conversely, treatment with an autophagy inhibitor decreased LC3II expression. Pi stimulation dysregulated the expression of several miRNAs such as miR-18a, miR-21, miR-23a, miR-30b, and miR-31a. However, miR-30b overexpression decreased Pi-induced expression of autophagy-related marker genes such as BECN1, ATG5, and LC3b, whereas miR-30b downregulation increased Pi-induced expression of these genes. In addition, we found that miR-30b directly targeted BECN1. CONCLUSIONS: These data suggest that miR-30b plays an important role in the regulation of high Pi level-induced autophagy in VSMCs by targeting BECN1.


Asunto(s)
Aorta Torácica/metabolismo , Autofagia/efectos de los fármacos , Beclina-1/genética , MicroARNs/genética , Proteínas Asociadas a Microtúbulos/biosíntesis , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/patología , Autofagia/genética , Beclina-1/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/biosíntesis , Proteínas Asociadas a Microtúbulos/genética , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Fósforo/farmacología , Ratas
10.
BMC Med Genet ; 18(1): 95, 2017 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-28851298

RESUMEN

BACKGROUND: A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus (DM) patients. Nevertheless, the results are inconclusive and inconsistent. METHODS: We screened PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Wanfang databases for those relevant studies updated in May 2016. RESULTS: 7 studies involving 2564 subjects were recruited. We evaluated the genotypic and allelic differences between DN patients and DM controls. Overall analysis showed that no significant association was found among the ApaI, BsmI, FokI,TaqI gene polymorphisms and DN susceptibility in diabetic patients (all P values > 0.05). In the stratified analysis, TT genotype was related to DN susceptibility in Asians (TT vs Tt + tt: OR =2.21, 95% CI: 1.05-4.67, p = 0.04). The sensitivity analysis showed that the results in overall populations, Caucasians and Asians were dependable. CONCLUSIONS: No significant association was found among the ApaI, BsmI, FokI, TaqI polymorphisms and DN risk in overall populations, the TaqI variants might related to DN susceptibility in Asians. Further researches are required to testify our meta-analysis.


Asunto(s)
Nefropatías Diabéticas/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Humanos
11.
Biotechnol Lett ; 39(8): 1159-1166, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28470626

RESUMEN

OBJECTIVES: To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine. RESULTS: C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 µg/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4+ T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-γ (458 ± 98 pg/ml), a typical Th1 cytokine. IFN-γ-expressing CD8+ cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization. CONCLUSIONS: A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.


Asunto(s)
Aciltransferasas/inmunología , Adyuvantes Inmunológicos , Antígenos Bacterianos/inmunología , Interferón gamma/inmunología , Proteínas Recombinantes de Fusión/inmunología , Vacunas contra la Tuberculosis/inmunología , Vacunas de ADN/inmunología , Aciltransferasas/química , Aciltransferasas/genética , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/genética , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas , Clonación Molecular , Células HEK293 , Humanos , Interferón gamma/química , Interferón gamma/genética , Ratones , Ratones Endogámicos C57BL , Plásmidos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Bazo/citología , Tuberculosis , Vacunas contra la Tuberculosis/química , Vacunas contra la Tuberculosis/genética , Vacunas de ADN/química , Vacunas de ADN/genética
12.
Cell Physiol Biochem ; 38(5): 1831-40, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27160248

RESUMEN

BACKGROUND/AIMS: Pioglitazone is a type of peroxisome proliferator-activated receptor x03B3; agonist and is capable of alleviating renal ischemia-reperfusion injury. METHODS: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. RESULTS: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. CONCLUSION: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.


Asunto(s)
Antioxidantes/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/irrigación sanguínea , Riñón/metabolismo , Malondialdehído/análisis , Nefrectomía , Óxido Nítrico/análisis , PPAR gamma/metabolismo , Pioglitazona , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Superóxido Dismutasa/análisis , Tiazolidinedionas/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismo
13.
Int J Mol Sci ; 17(8)2016 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-27529235

RESUMEN

Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-ß/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-ß/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-ß/Smad/EMT signaling activity.


Asunto(s)
Berberina/uso terapéutico , Riñón/efectos de los fármacos , Animales , Western Blotting , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Estreptozocina/toxicidad , Factor de Crecimiento Transformador beta/metabolismo
15.
Am J Nephrol ; 41(1): 28-36, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25634106

RESUMEN

AIMS: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. METHODS: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/ß-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of ß-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. RESULTS: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/ß-catenin pathway and ß-catenin activity. ß-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that ß-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that ß-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of ß-catenin in the rat model was investigated, we found that aortic calcification was reduced. CONCLUSION: These results suggest that ß-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.


Asunto(s)
Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Fósforo/farmacología , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Actinas/genética , Actinas/metabolismo , Animales , Aorta , Nitrógeno de la Urea Sanguínea , Calcio/sangre , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Creatina/sangre , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Masculino , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Nefrectomía , Osteopontina/genética , Osteopontina/metabolismo , Fósforo Dietético/metabolismo , Plasmalógenos/sangre , Ratas , Ratas Sprague-Dawley , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/metabolismo , Calcificación Vascular/etiología , beta Catenina/genética
16.
Environ Technol ; 36(9-12): 1433-40, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25428576

RESUMEN

In order to remediate ammonium contaminated groundwater, an innovative multimedia permeable reactive barrier (M-PRB) was proposed, which consisted of sequential columns combining oxygen releasing compound (ORC), zeolite, spongy iron and pine bark in the laboratory scale. Results showed that both ammonium and nitrate could be reduced to levels below the regulatory discharge limits through ion exchange and microbial degradation (nitrification and denitrification) in different compartments of the M-PRB system. The concentration of dissolved oxygen (DO) increased from 2 to above 20 mg/L after the simulated groundwater flowed through the oxygen releasing column packed with ORC, demonstrating that ORC could supply sufficient oxygen for subsequent microbial nitrification. Ammonium was efficiently removed from about 10 to below 0.5 mg N/L in the aerobic reaction column which was filled with biological zeolite. After 54 operating days, more than 70% ammonium could be removed by microbial nitrification in the aerobic reaction column, indicating that the combined use of ion exchange and nitrification by biological zeolite could ensure high and sustainable ammonium removal efficiency. To avoid the second pollution of nitrate produced by the former nitrification, spongy iron and pine bark were used to remove oxygen and supply organic carbon for heterotrophic denitrification in the oxygen removal column and anaerobic reaction column separately. The concentration of nitrate decreased from 14 to below 5 mg N/L through spongy iron-based chemical reduction and microbial denitrification.


Asunto(s)
Compuestos de Amonio/metabolismo , Agua Subterránea , Contaminantes Químicos del Agua/metabolismo , Purificación del Agua/métodos , Adsorción , Compuestos de Amonio/química , Biodegradación Ambiental , Desnitrificación , Agua Subterránea/química , Concentración de Iones de Hidrógeno , Intercambio Iónico , Hierro/química , Nitrificación , Oxígeno/análisis , Pinus , Corteza de la Planta , Contaminantes Químicos del Agua/química , Zeolitas/química
17.
ScientificWorldJournal ; 2014: 624573, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25184149

RESUMEN

OBJECTIVE: This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). METHODS: We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. RESULTS: Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. CONCLUSION: Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients.


Asunto(s)
Nefropatías Diabéticas/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Factor A de Crecimiento Endotelial Vascular/genética , Alelos , Genotipo , Humanos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple
18.
Pharmazie ; 69(12): 904-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25951664

RESUMEN

This study aimed to investigate the protective effect of metformin on renal injury of C57BL/6J mice treated with a high fat diet. High-fat diet for 12 weeks was used to establish the mice model of metabolism syndrome and the intervention of metformin (75 mg x kg(-1) x d(-1)) for 4 weeks, and plasma biochemical indicator and body weight were used to evaluate the model. Sterol regulatory element-binding protein (SERBP)-1c, TNF-α, NADPH Oxidase (NOX)4 mRNA was determined by real time-PCR. Phospho-AMP-activated protein kinase (P-AMPK)α protein was detected by western blotting. Oil Red O staining, Masson staining and HE staining were for observing renal pathological changes. At the end of 12th week, compared with mice on low fat diet (LFD), body weight (BW), the levels of fasting insulin (FINS), plasma and renal triglyceride (TG) were higher and plasma high density lipoprotein (HDL) and insulin sensitivity index (ISI) were significantly lower, but the levels of fasting blood glycemia (FBG), plasma total cholesterol (TC) and renal TC had no changes; Oil Red O staining revealed renal lipids deposition, Masson staining and HE staining revealed glomerular hypertrophy, matrix increasing, and inflammatory cells infiltration in glomerular; the expression of p-AMPKα protein decreased and the expression of SREBP-1c, TNF-α, NOX4 mRNA increased significantly in mouse treated with high fat diet (HFD). Compared with the HFD group, through metformin interventing, metabolic disorders were significantly improved, renal lipids deposition and other pathological changes were ameliorated, the expression of p-AMPKα protein increased and the expression of SREBP-1c, TNF-α, NOX4 mRNA decreased significantly. Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-α, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Dieta Alta en Grasa/efectos adversos , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Lesión Renal Aguda/patología , Animales , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Riñón/metabolismo , Riñón/patología , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Nefritis/patología , Nefritis/prevención & control , Estrés Oxidativo/efectos de los fármacos
19.
Front Microbiol ; 15: 1347293, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686105

RESUMEN

The mixture of whole-plant soybean and whole-plant corn silage (WPSCS) is nutrient balanced and is also a promising roughage for ruminants. However, few studies have investigated the changes in bacterial community succession in WPSCS inoculated with homofermentative and heterofermentative lactic acid bacteria (LAB) and whether WPSCS inoculated with LAB can improve fermentation quality by reducing nutrient losses. This study investigated the effect of Lactobacillus plantarum (L. plantarum) or Lactobacillus buchneri (L. buchneri) on the fermentation quality, aerobic stability, and bacterial community of WPSCS. A 40:60 ratio of whole-plant soybean corn was inoculated without (CK) or with L. plantarum (LP), L. buchneri (LB), and a mixture of LP and LB (LPB), and fermented for 14, 28, and 56 days, followed by 7 days of aerobic exposure. The 56-day silage results indicated that the dry matter content of the LP and LB groups reached 37.36 and 36.67%, respectively, which was much greater than that of the CK group (36.05%). The pH values of the LP, LB, and LPB groups were significantly lower than those of the CK group (p < 0.05). The ammoniacal nitrogen content of LB was significantly lower than that of the other three groups (p < 0.05), and the ammoniacal nitrogen content of LP and LPB was significantly lower than that of CK (p < 0.05). The acetic acid content and aerobic stability of the LB group were significantly greater than those of the CK, LP, and LPB groups (p < 0.05). High-throughput sequencing revealed a dominant bacteria shift from Proteobacteria in fresh forage to Firmicutes in silage at the phylum level. Lactobacillus remained the dominant genus in all silage. Linear discriminant analysis effect size (LEFSe) analysis identified Lactobacillus as relatively abundant in LP-treated silage and Weissella in LB-treated groups. The results of KEGG pathway analysis of the 16S rRNA gene of the silage microbial flora showed that the abundance of genes related to amino acid metabolism in the LP, LB, and LPB groups was lower than that in the CK group (p < 0.05). In conclusion, LAB application can improve the fermentation quality and nutritional value of WPSCS by regulating the succession of microbial communities and metabolic pathways during ensiling. Concurrently, the LB inoculant showed the potential to improve the aerobic stability of WPSCS.

20.
J Vasc Surg ; 57(2): 547-567.e8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23337863

RESUMEN

BACKGROUND: Junctional vascular trauma such as that at the thoracic outlet poses particular challenges in surgical management. The use of endovascular techniques for such injuries is attractive as repair may be facilitated without the need for thoracotomy; however, the utility of such techniques is currently based on opinion, small retrospective series, and literature reviews of narrative and not systematic quality. The objective of this study is to provide a complete and systematic analysis of the literature pertaining to open surgery (OS) and endovascular management (EM) of thoracic outlet vascular injuries. METHODS: An electronic search using the MEDLINE, Embase, Cochrane Library, Science Citation Index, and LILACS databases was performed for articles published from 1947 to November 2011. The review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement standards. Prospective studies and retrospective cohorts of more than 10 patients were included. The primary outcome was all-cause mortality. RESULTS: One prospective noncomparative study and 73 retrospective series met the inclusion criteria. There were no randomized studies. All studies were at high risk of bias. Fifteen studies described outcomes for both OS and EM (549 patients). The majority of these studies described EM for traumatic arteriovenous fistulas or false aneurysms in stable patients. Direct comparison between OS and EM was possible in only three studies (comprising 23 OS and 25 EM patients), which showed no difference in all-cause mortality (odds ratio, 0.67; 95% confidence interval [CI], 0.11-4.05), but a shorter operating time with EM (mean difference = 58.34 minutes; 95% CI, 17.82-98.85). These three series included successful EM of unstable patients and those with vessel transection. There were 55 studies describing only OS (2057 patients) with a pooled mortality rate of 12.4% (95% CI, 9.9%-15.2%). Four studies described only EM (101 patients) with a pooled mortality rate of 26% (95% CI, 8%-51%), but these represented a distinct subgroup of cases (mainly iatrogenic injuries in older patients). CONCLUSIONS: The current evidence is weak and fails to show superiority of one modality over the other. EM is currently used primarily in highly selected cases, but there are reports of a broader applicability in trauma. High-quality randomized studies or large-scale registry data are needed to further comment on the relative merits or disadvantages of EM in comparison to OS.


Asunto(s)
Aneurisma Falso/terapia , Fístula Arteriovenosa/terapia , Procedimientos Endovasculares , Extremidad Superior/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares , Lesiones del Sistema Vascular/terapia , Adulto , Aneurisma Falso/etiología , Aneurisma Falso/mortalidad , Aneurisma Falso/cirugía , Fístula Arteriovenosa/etiología , Fístula Arteriovenosa/mortalidad , Fístula Arteriovenosa/cirugía , Causas de Muerte , Distribución de Chi-Cuadrado , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Enfermedad Iatrogénica , Masculino , Oportunidad Relativa , Selección de Paciente , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/mortalidad , Lesiones del Sistema Vascular/cirugía
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